From the immediate assault of stress to the long term management of stress response
]]>At the heart of almost every health and mental health issue is stress.
An exhaustion of stress response in the body and brain to be exact.
This can be sudden (trauma or infection) or a slow grinding down (chronic) but either way, the repercussion is intimately tied to every health issue.
The two biggest drivers of drug relapse???
The problem with many of our stress release valves (alcohol, cannabis, benzos, etc) is that they build tolerance over time.
Your stress response system actually gets dialed down with use! Going the wrong way.
CBD isolate doesn't actually have this effect! Let's dive into how it works for stress response with this in mind!
A quick intro to the feedback effect of CBD isolate:
Okay…lots of heavy lifting. Let's get to it!
First, stress is not the enemy.
Stress is just a signal that something is wrong…it's there to drive one of 2 actions:
Stress is just a signal that the current path is not ideal for our well-being.
Great…but occasionally, the source of stress is out of our control and our natural systems to address it are exhausted.
We could use some support in the meantime! We have a massive review of Top 10 Tips for Stress Support but we're going to zero in on one critical player..CBD isolate.
CBD works in the endocannabinoid system but how it works is the key.
Unlike THC (its cousin) which pushes in one direction, CBD acts like a feedback mechanism!
We'll dig into the mechanics of it below but this subtle effect is so important to long term stress response.
We don't throw a wet blanket on stress just to have it rebound even stronger!
But…we need some support when outgunned.
Hello CBD! Massive reviews on CBD and stress response or CBD and resilience but let's drill down into CBD and stress pathways directly.
A quick intro to the stress players. First the "bad" guys:
And the opposing forces?
Okay…the field is set. Let's play ball!
We'll start with the monster players. Frontline stress response.
GABA is front and center and just happens to be the target of benzos (till tolerance and addiction send things the other way).
GABA is our brain's "brake" pedal and it's intimately tied to calm, sleep, and all versions of slowing down.
Stress directly eats up GABA so this is the first shoe to drop.
CBD is a positive allosteric modulator of GABA. Translation:
It supports when running low!
CBD interacts with CB2 receptors and they're all over GABA function:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
We have a whole review on CBD and GABA but the key takeaway is…
GABA is the "right here and now" controller of stress (hence the benzo effect) and CBD supports it when low.
Remember that CBD's original "discovery" was around seizures which reflects a massive imbalance between GABA and its opposing force…glutamate.
Magnesium glycinate is also a great support mechanism here.
What about longer term stress management?
Hello, serotonin!
If GABA is the here and now player, serotonin is the tomorrow and next Wednesday operator.
Serotonin is the manager of ALL human behavior…including how we deal with stress.
In fact, it's a powerful stress (and pain and inflammation) response buffer.
CBD also acts as a feedback mechanism when it's becoming exhausted by stress.
Our favorite study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Let's translate…
An injury causes pain which quickly exhausts serotonin and leads to systemwide pain and anxiety.
CBD…
The key word there is "rescue" since too much serotonin can be even worse than not enough! See serotonin syndrome.
Stress exhausts serotonin. CBD supports levels when low.
Check out our big review on CBD and serotonin or serotonin as a social stress buffer.
Tryptophan may also be a support here.
Let's turn to the background nervous system.
Acetylcholine is the key component of our "rest and digest" or parasympathetic nervous system.
Notice how your heart races, your pulse quickens, and your palms can get sweaty under serious stress?
That general feeling of "frazzled" is your body's response to stress and is the autonomic nervous system.
Adrenaline! The pushback?? Acetylcholine.
Your "calm and focused" player released from the vagus nerve behind your chest plate (ever wonder why meditation, deep breathing, and gratitude helped??)
More on supporting the vagus nerve here but what about CBD and acetylcholine through its hub, the vagus nerve?
https://pubmed.ncbi.nlm.nih.gov/32965166/
So CBD supports the hub of rest and digest (calm and focus) and cannabis (THC) offset this.
Interesting! See why CBD is so important to protect against the excesses of THC.
We have a whole review on vagus nerve support and CBD and acetycholine.
Let's turn to a key opponent you may not even know about!
Histamine is fascinating. Sure, it's the primary allergic reaction driver but it does so much more in the brain…especially during stress.
When you have acute stress, the body just gushes out histamine from mast cells:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2343625/
IL1 is an inflammatory cytokine. CRF??? Just the instigator of the stress response…corticotrophin releasing factor.
So stress drives histamine which is excitatory in the brain.
In fact, the first class of anti-anxiety meds were…anti-histamines! See CBD versus anxiety meds.
Extreme histamine release feels just like anxiety.
So…CBD isolate there?
There are lots of examples where CBD calms mast cell activation (asthma, brain inflammation, gut inflammation, etc) but one example from endometriosis:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141153/
Important note….this is CBD isolate. NOT full spectrum and not THC.
See CBD versus full spectrum for histamine to learn why.
Also, for ladies, check out why progesterone is so important for mast cell activation.
One note…histamine directly opposes GABA so your first stress response buffer is getting hit hard when histamine flares up.
Big guide to histamine if this is your issue.
Next up…deep in the endocannabinoid garden that CBD plays in.
Anandamide is one of 2 primary endocannabinoids we naturally in have in our bodies.
Named after Anand, the Hindu goddess of "bliss", it's called on reserve when stress is winning.
THC mimics anandamide but too hard and for too long so there's a rebound effect (and eventual tolerance).
CBD supports anandamide when low…again, the feedback mechanism as an allosteric positive modulator.
It does this by blocking the chemical called FAAH that breaks down anandamide.
Let's take an example of extreme (maybe the most extreme) stress response imbalance…psychosis:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
We have a massive review on CBD and anandamide or even CBD and psychosis since extreme stress can push us to our breaking point.
That's the "hero's" list….let's get back to the "bad guys" of stress.
Glutamate, as the "gas" pedal of the brain, is essential but too much is downright toxic and more importantly, overwhelms GABA.
So…short term:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645314/
Okay…so stress drives the gas pedal. Makes sense (danger! Get going) but it doesn't feel great.
Longer term???
https://www.frontiersin.org/articles/10.3389/fnhum.2021.722323/
Okay…so too much of a good thing is very bad.
One note…the immune system (inflammation) can just gush out glutamate when hyperactivated…more on that below (point #10).
Love this study because it speaks to the feedback operation of CBD.
They looked at CBD's effects on GABA/glutamate balance between people with autism and a control group.
First...
https://www.nature.com/articles/s41386-019-0333-8
They found that CBD calmed glutamate but actually increased it in people with autism specifically in the prefrontal cortex (where activity is lacking with autism).
Two different effects depend on the "state" of brain areas. See CBD and autism or CBD and glutamate to learn more.
Magnesium glycinate and NAC are also powerful protection against excess glutamate.
Now…the main stress player.
Cortisol = stress.
No getting around it…what does CBD do with cortisol since it's the powerhouse behind stress response.
A few key takeaways…
First…CBD's effect on cortisol for subjects nearing their breaking point:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
Also…
So…THC can actually increase cortisol (our bet is on histamine response) and CBD counters this. The original meaning of the "entourage effect". See CBD to protect against THC.
Another study looked at CBD's effect on people who are pre-psychotic…stress response is almost breaking…while undergoing public speaking test (sounds like torture):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113209/
To translate…
CBD brought their cortisol levels to in between untreated (max cortisol) and control group (normal response - not pre-psychotic)!
Away from the edge!
See CBD and cortisol or CBD and stress response.
Let's go back to the start of all of this (stress response).
Remember that CRF starts the whole stress ball rolling.
There's a fascinating tie between serotonin and CRF. In fact, for the first two weeks of starting an SSRI (See CBD versus SSRI), CRF and anxiety can actually INCREASE!
What about CBD and our stress initiator?
https://journals.sagepub.com/doi/full/10.1177/0269881118805495
This speaks to a low-level, maintenance regiment of CBD to keep stress from exploding.
We'll discuss dosages below.
We have a whole review on CBD and corticotrophin releasing factors.
One more stop.
All the new exciting research on stress response and anxiety centers around brain energy. In fact, check out the book by that name.
Mitochondria (our cellular power plants) are master regulators of brain function and when they go astray, bad things happen in the stress department.
One big result is increased inflammation and oxidative stress!
Literally, little oxygenated assassins…like running with scissors throughout your sensitive brain material!
This is bigger than stress.
If we don't get the whole stress complex (HPA axis) under control, it leads to damage and aging of the brain:
https://pubmed.ncbi.nlm.nih.gov/23490070/
CBD there?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/
Several models indeed.
Check out our full review of CBD and oxidative stress or CBD and mitochondria.
One final but very important note before looking at a stress regiment.
Here's the skinny…early trauma, infection, or stress can dysregulate EVERYTHING we listed above.
Goodness…your stress response is literally hijacked and you're "set" to a constant state of vigilance!
We have a whole review on editing your mental health past or how the immune system is the key to mental health.
This may speak to why some people can handle stress better than others and there are ways to "edit" these changes out of our epigenome (where it's stored).
Check out the Top 10 Tips for Stress Response with other important tools that don't build tolerance, addiction, or have nasty side effects.
Our CBD Stress Response QuickStart Guide:
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Is Delta 8 really safe? Our brief interaction was anything but!
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We're deeply embarrassed by our industry.
Yes, the CBD industry!
The embrace of Delta 8 speaks to everything that's wrong with how Americans and businesses view health.
We already go into the research on why Delta8 should not be legally available on the market based on science but our story is more personal.
Let's also look at why the CBD industry is chasing Delta8 short-term at the expense of everything positive that can be gained from high-quality CBD isolate.
We'll also dovetail in the all-important concept of tolerance…a simple word for tachyphylaxis or how pushing pathways too hard up or down always ends up poorly.
Just look at benzos or SSRIs if you need an example. Or opioids??
Again, we have a full review comparing CBD isolate and Delta8 already.
This is much more personal.
About 1 month, I came across a packet of gummies that had been sent to us from a trusted CBD supplier as a sample
It had been in the drawer on my desk for a few months so I didn't really recognize it.
We have CBD isolate gummies which are great in a pinch when under stress (see CBD and stress).
The packet looked different (black) but when I scanned the label, I saw CBD so I assumed it was just another CBD isolate product which is primarily what they supply us with.
It said 10mg CBD and there were four samples so I took all four. 40mg of CBD isolate after all is no big deal. Neurogenesis is clocked at 300mg daily with no psychoactive effect.
Again, that's the whole point of CBD isolate (not full spectrum).
This was around 11 am in the morning. My spouse and I go swimming every day at around noon.
I'm driving over and when we get to the parking lot of the gym, I realized that I had no recollection of driving over.
Like I had slept-walk my way over! My vision tracking became slow and my first thought was that I was having a migraine which usually starts with acute tunnel vision.
This just felt different though. I actually thought I was having a stroke! This wasn't a migraine (none of the usual numbness in my left hand which presages the migraine.
My spouse drove us both back home thinking it was a migraine but I was really worried. Felt like I was melting.
Completely forgot about the gummies till later when my spouse asked me if there was anything I ate that might have caused the "migraine".
I later remembered the gummies and she went to get the package out of the trash.
Below the "10mg CBD" was a smaller font with "10mg Delta8". Per gummy!
So I had just ingested 40mg of Delta8 as an edible.
I was partially relieved that it wasn't a stroke and not even a migraine. That relief didn't last long.
I tried to lie down but I kept feeling like I was falling and then I would SNAP up in a burst of anxiety.
Time was distorted so these cycles of anxiety and sinking felt like they were every 15 minutes but when I looked at the clock, maybe 1-2 minutes had passed.
I tried to take a bath and it was the same. Just horrible..fading out and then gasping into anxiety periodically.
Look…we tried all the tricks to help with "greening" out.
Nothing was working. I was going to have to get through the next 6-8 hours of hell.
And I do mean hell.
I was angry now. I'm a 190-pound person in good health with a great functioning liver (where Delta8 is processed).
When I was driving, that could have been very dangerous. No recollection at all of the trip over. Autopilot.
What if kids got ahold of these gummies (happens every day…see hospital entries).
Here's the issue...somehow, Delta8 is legal!!
Yes, legal and it's clearly not some benign version of THC (Delta9 technically).
We won't work with a supplier that also sells Delta8 out of principle but that's becoming a small list of ethical companies for us to choose from.
In fact, a company's effort to sell Delta8 is a huge red flag for us.
What gives?
There was an explosion of CBD activity around 2018. Everyone and their mothers jumped into the business and many were simply after a quick buck.
We found CBD as a result of a brutal perimenopause crisis (that story here) and wanted to source CBD isolate from the cleanest source at the lowest cost per mg of CBD.
This is based on what we found after about 1 thousand hours of NIH research. It's all right there!! (and right here).
Then the pandemic hit and everyone was flush with extra cash. CBD sales when through the roof as did legal cannabis and alcohol.
People were stressed. People were bored. People were looking for relief.
Around the last half of 2022, the market started to crash. All the quick-buck brands and companies that flooded the market started to die off.
One supplier told us (as they were closing shop) that 90% of their customers had left the market during 2022.
The remaining brands panicked. They started offering Delta8 which is a known psychoactive cousin with similarities to THC but somehow, escaped the FDA's net on legality.
CBD, when sourced correctly (THC under .3%) is legal…treated like a food supplement. This makes sense when you understand how it works.
THC was the boogeyman (we get it…see THC versus CBD here). Somehow, Delta8 snuck through the CBD backdoor and was legal on the market.
It was only when the CBD market imploded that the brands started pushing Delta8 (sometimes branded as THC since they both have that general monicker). Delta8 versus Delta9.
They were going out of business and they sold out! Sure, we'll sell a psychoactive product online with a simple "Are you 21" click button.
Shame on them. After what I went through, they're cutting their nose to spite their face and the FDA can't come quick enough (more on that below).
Alright…maybe it was just us? What's the research behind any of this?
In the cannabinoid world, you have three basic actions:
Agonists push activity up. Antagonists push activity down.
Both cause "overshoot" with higher levels (like what I felt in the bath).
Short term, this can lead to all sorts of "side effects". There are no side effects. There are only "Effects".
Longer term, you build tolerance which means the body will push that same pathway the other way!
So…if THC relaxes you initially, with time, it will make you prone to anxiety and THC freak-outs!
Check out the review of why THC causes freak-outs.
That is the reason we're so impressed with CBD isolate! It works like a feedback mechanism for key pathways when exhausted.
Learn more about how CBD works here.
Clearly, after our experience, Delta8 is an antagonist and pushes activity too high. Don't take our word for it.
https://pubmed.ncbi.nlm.nih.gov/35523678/
So…why is this legal? What if I was driving a bus and I took these "legal" gummies or what if children found the "Gummies". Don't get us started on the edible, colorful form factor for these Delta8 products.
Delta8 really shouldn't be legal the way it is now.
This is a clear example of where FDA regulation should crack down and not the legitimate CBD isolate market (Full spectrum CBD is somewhere in the middle).
In fairness, the FDA has made Delta8 a target for possible regulation but to date, there's no real movement and we're seeing some pretty big CBD brands slog Delta8 (referenced as THC which technically is true) gummies all over their website.
Just click age 21 or older and buy away!
Good luck with that one.
Longer term (generally pushed for sleep or pain), those pathways will just get worse and worse with time.
Sorry…that's the truth for tolerance whether Ambien or Valium or oxycodone or Tylenol.
Or Delta8.
Hopefully, our experience is a warning. Even in slow-mo (smaller dose), it's the wrong direction if you truly want to feel better long term.
]]>Tolerance causes long term effect to key stress response pathway which may be able to be reversed
]]>Look, we're not here for the cannabis is medicine debate. We stick to the research and anyone who's used cannabis longer term or knows someone who has can agree…
The ability to deal with stress can get blown out!
Freakouts. Blow ups. Meltdowns. Emotional explosions. However, you want to name it.
There are actually good explanations for this effect longer term and two suspects are in play:
One is the here and now (serotonin), while the other is long term structural (the hippocampus).
Understanding how THC's effects build over time at these two crucial junctions and more importantly, how to offset the effect or better yet, find tools that support our stress response is key to feeling better.
We'll also touch on why THC may have felt so right to begin with and ways to address that differently and don't worry, we'll finish on a positive note!
Here are the topics we'll cover:
Let's get started before someone cuts you off onthe highway again (you know who you are!)
We have lots of deep dives on THC such as CBD to protect against THC.
Many people are initially drawn to cannabis with THC because of stress so what flips?
First, we need to understand what THC is doing in the brain.
THC mimics a natural substance we have called anandamide which is named after the Hindu goddess of…Bliss.
Yes, bliss. The opposite of stress.
Anandamide is our "natural" high. Feeling pretty good and at peace for lack of a better word.
It works primarily at a receptor called CB1 in our endocannabinoid system which is tasked with balancing every other key system.
So…when we get stressed, this system brings things back to normal. We can't stay in that state long term without adversely affecting our health.
In fact, we looked at whether exhausted or poorly functioning endocannabinoid systems is key to most modern diseases. Answer…yes. Or it's a part of it.
So…this should all be good with THC right? In fact, most people speak to a relaxing effect from cannabis unless you're one of the 30ish% that has a histamine response to it (panic attacks, anxiety, paranoia, etc).
Here's the problem with THC.
It's a full blown agonist for CB1 activity. It pushes in one direction and it hits harder and lasts longer than the natural anandamide.
That's the "high" and other symptoms of cannabis use (foggy thinking, slowed reactions, etc).
The brain doesn't like meddling in such a key pathway so it will slowly start to downregulate CB1 receptors and sensitivity over time.
We see this with most drugs in fact (see tolerance review).
This means our natural production of anandamide is slowly getting whittled down.
A big problem! Anandamide works like a big wet blanket in the brain on:
We looked at whether people used THC chronically to slow things down in the brain initially.
So…why bring up serotonin?
Serotonin is the manager of ALL human behavior. Seriously.
Think of waves of stress response buffers:
All those medication classes build tolerance (benzos add in addiction) which means your natural levels will just keep dropping.
Let's focus on serotonin since it's the ringleader for mood.
First, we know there are issues with THC exposure during brain development (sorry…up to age 25):
https://academic.oup.com/ijnp/article/23/11/751/5877833
At high levels, it can actually look like serotonin syndrome (too much serotonin -very dangerous):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220016/
Serotonin syndrome may speak to a freakout caused not so much by long term use (slow whittling) but to taking in too much THC in one setting (greening out).
They're seeing lots of that in ERs these days where cannabis is legal and/or much more potent.
Edibles are a big driver of this trend.
The main driver:
So…short term, it's like a giant SSRI with the rebound expected when serotonin is exhausted.
Longer term though….watch what happens.
First, the mechanism:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027478/
Okay…so THC drives dopamine and serotonin activity.
But chronic use?
Blunted. The brain doesn't like the firehose of CB1 activity and will actually ratchet it down just like the volume (or better yet…equalizer) on a stereo (I date myself).
People...dopamine is your "verve" pathway.
This means your natural feel-good pathway (anandamide) and mood manager and drive manager are slowly losing volume in the brain.
People…this is your main line of defense against stress!
At some point, you're just using cannabis to not feel terrible (as opposed to feeling high or really good).
Roughly 9% of people who use THC get addicted but probably 100% will feel the tolerance with longer term use.
Two different types of suffering really with pure addiction leaning heavily on the dopamine system.
Later, we'll look at ways to naturally support serotonin, dopamine, and anandamide.
Let's turn to actual brain areas now. We'll zero in on tied to mood freakouts.
Mood's a complicated thing but if there's one brain area with direct control, it's the hippocampus.
Part of our older "reptilian" brain, this area is in charge of both memory (THC impairs) and…mood control.
Analyzing the situation and deciding on how to respond.
"Everything's going to be okay or….Freak the #%)& out!"
We're going to hit just fascinating highlights (of many).
https://www.frontiersin.org/articles/10.3389/fnhum.2019.00242/full
Okay…emotional regulation. The opposite of losing your shit.
Here's the problem…the hippocampus is one of the most vulnerable areas to many assaults in the brain:
The memory side of its job description makes it very malleable…able to change all day long. This same flexibility makes it subject to damage from the list above.
THC specifically (but with a silver lining):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068875/
Lower volume = poorer mood control:
https://www.sciencedirect.com/science/article/pii/S2667174321000471
"In response to stressful life events."
People…THC is not the way longer term for mental health.
We're not even looking at the prefrontal cortex which keeps our fears and impulses at bay:
https://www.sciencedirect.com/science/article/pii/S1878929315000699
Or…the white matter tracts that link all brain areas so we can think cohesively:
https://www.sciencedaily.com/releases/2015/11/151127102333.htm
Longer term, tolerance is the enemy of most medications and THC.
So…what to do?
Some people are just drawn to THC. From the get-go…it hits "the spot".
That "spot" is what we want to focus on.
There can be chemical and genetic differences surrounding the endocannabinoid system but our money is on the past.
Past trauma, stress, and infection.
Here's the secret code that we're all walking around with inside of us.
Early stress, trauma, and or infection (even in utero or past generations) can directly affect all these pathways and how we respond to…stress!
So…Serotonin.
https://pubmed.ncbi.nlm.nih.gov/32981537/
And anandamide (probably exhausted from serotonin running low):
https://pubmed.ncbi.nlm.nih.gov/31849055/
Goodness. We have deep dives into how much of this resides in the immune system and how to edit it out here.
The brain's a prediction machine and it doesn't like being surprised…again, so vigilance gets built into the system.
We looked at this process in detail in our Is THC use tied to excess glutamate?
The best set of tools we can find that don't build tolerance can be found at our Tapering THC Tips guide.
A quick primer.
First, you have to address the original sin above (the priming).
This means focusing on the immune system where past misdeeds are recorded.
If psilocybin is not ready for prime-time (it's coming!!) the medicinal mushrooms are interesting there.
Interestingly, there's a lot of overlap between our Tapering SSRIs and Tapering THC (go figure…hello Serotonin).
Most importantly, these don't build tolerance which is what got us into the freakout mess with THC to begin with.
Of course, we found all this due to the relationship of CBD and THC.
The original meaning of "the entourage effect" was how CBD would counter many of the negatives of THC.
You see it all over the research such as:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908414/
People…that's the hippocampus!
Remember, this is where structural damage (loss of volume) occurs in the brain from THC longer term.
And serotonin:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
The key word there? "Rescues impaired 5-HT"
5-HT is code for serotonin. We have a big review on CBD and serotonin here or how CBD protects the brain from THC.
It's definitely in the toolkit you can find at our Tapering THC Guide.
Again…sorry. We want it to work longer term as well but we get emails all the time from people who find themselves blowing up on our significant others, coworkers, kids, or parents.
Now you know why.
Lots of bad news above. Brain structure?
Let's wrap on a positive note.
Did you catch that last note in one of the dire study results?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068875/
Long-term cannabis users. And then…
"Atrophy can be restored following prolonged abstinence"
Atrophy literally means brain shrinkage. Structural volume reduction! Of the brain!
We see this across many studies and here's the net net.
After about 30 days of abstinence, the CB1 receptors will start to come back online. In fact, many of the deficits from long term THC use can revert.
This is amazing. And very hopeful. Check out the tapering article!
Just a side note…starting as an adolescent and/or consuming massive amounts of cannabis may make this repair piece harder. Longer.
The key to support neurogenesis and we have a whole review on that here.
The ridiculous guide to CBD and anxiety
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
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First, a shout out to Andra (@BioavailableNd) for bringing this superstar to our attention.
And we do mean superstar!
Everything's about timing and our introduction to lactoferrin so soon after a deep dive into blood donation and longevity/health speaks to this.
Both revolve around the powerful sway (both good and bad) of iron.
Lactoferrin's effects are so varied and powerful that it begs the question…is lactoferrin a key reason mammals are so successful?
We'll leave the philosophical questions for another day and instead, dive into the many different effects of lactoferrin across the body and brain:
Let's get started!
Lactoferrin is a protein that's constantly released from any mucous source with a strong influence on breast milk for mammals.
Tears, saliva, semen, vaginal fluid, lung/nasal fluid. All "wet" interactions between our inner body and the harsh outside world is going to get a handshake from lactoferrin.
There's a reason for this!
You can think of lactoferrin as a "consultant" of sorts for key systems of our body….with the immune system being front and center.
This explains why it's everywhere our body is vulnerable to outside microbes….bacteria, viruses, and the like which would love to gain entry.
We say "consultant" because its effects do not push in just one direction. This is so sooo important.
One of the reasons we love CBD isolate is that its effect can change depending on the state of the system. Bi or even tri-phasic. Cancer is a perfect example of this.
Lactoferrin doesn't just ramp up the immune system in response to attackers. It can also resolve the immune response!
Okay…you have our attention. This is a very special trick and we rarely find it in the world of supplements, medications, or even natural bodily substances.
Lactoferrin doesn't have a classic endocannabinoid pathway (tasked with balancing other systems) but nonetheless, it helps the body manage key pathways depending on the needs at the time.
Just fantastic in our books!
So…let's slowly build the case for this superstar. Starting at the start.
The name literally means iron (ferro) and milk (lacto). It's not a source of iron but a "manager" of it.
Ridiculously powerful in fact:
https://www.jpeds.com/article/S0022-3476(16)00295-X/fulltext
Indeed, it's a major contributor to colostrum from mother's milk in mammals.
You can even get it from cow's milk (if you're wondering why you're craving it!!) with a pretty similar genetic recipe (689 versus 691 amino acids).
Lactoferrin is a complicated protein that has a very special gift around iron.
Iron is the second deal Nature made (after glucose) with the devil for life.
It's both the source of life on Earth (carries oxygen) and incredibly toxic (rust!!)
You're literally a controlled burn. It's amazing we exist at all and iron must be tightly managed.
Lactoferrin's first "consulting" gig is around iron balance.
Here's the fascinating piece we touched on above…it can have different results depending on the state of the system!
Lactoferrin is a powerful iron chelator…meaning it "sequesters" or binds up excess iron:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618634/
The ph piece is interesting as it speaks to states of disease, infection, and inflammation.
Lactoferrin is incredibly powerful at sponging up free-floating (destructive) iron.
So…does that lead to anemia…too little iron?
https://www.nature.com/articles/s41390-022-02136-2
A study compared giving lactoferrin versus iron itself and the results:
https://www.nature.com/articles/s41390-022-02136-2
Wait…what? Better iron profile for people with anemia than iron itself?
The key may be gut absorption where lactoferrin is a powerful manager and we'll touch on that below.
For now…know that lactoferrin's primary lever of choice is a tight and situational control of iron levels.
Iron just happens to be the "currency" of cellular activity (literally the burn of fuel) so the effects of this management…might be profound.
Let's then see how lactoferrin wields this weapon in its primary (and maybe first) role.
It turns out that viruses, bacteria, and other microbes need iron as well to flourish. They're actually pretty poor at sourcing it themselves (anaerobic) so they lean on our supply.
That's where lactoferrin comes in. In fact, this may be its original job description and speaks to why it's in breast milk and any other fluid where we meet the outside (hostile) world.
Its effect on bacteria/viruses is at first direct:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814036/
It "steals" iron from attackers. That's only the beginning.
It also coordinates (the consultant gig from above) our immune's response on the ground.
Summary level:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814036/
Oh goodness. "Mediator" for our immune response, both the original recipe (innate) and in response to new attackers (adaptive).
In fact, lactoferrin is released from immune players in response to infection to "ramp up" response.
But, and this is critical in times of cytokine storm and autoimmune, it also works the other way!
To resolve inflammation and immune response…as well as keep it from running amok (as dangerous as the bacteria/viruses themselves).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618634/
IIH? Oh, that's just iron and inflammatory homeostasis. Homeostasis means "balance."
Again…it assists our immune system in delivering the right response:
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01438/full
We really thought it would be an endocannabinoid player but this is separate…special to mammals (and fish???).
Let's take this for a spin.
What about autoimmune?
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01438/full
So…calm the immune storm and "resolve" inflammation.
Please…get specific…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836292/
Learn about autoimmune here.
So…that's just one example (of many) where the immune system is hyperactive and actually causing damage. Lactoferrin pushes back on this.
One note…our levels of lactoferrin go down with age (matching the increase of autoimmune) and there's a connection with female hormones (estradiol drives it) hence the gender difference with autoimmune (8:1).
So…a quick checklist:
Look…the immune gets complicated real quickly. Just one example of lactoferrin's multifarious effects:
https://www.mdpi.com/1420-3049/26/1/205
Uncle?? We bring this up to mention the Th1 and Th2 equation. These are system-wide immune "settings".
There's a delicate (and very complicated) dance between the two and lactoferrin definitely Tango's
As for the current virus-du-jour, we got in trouble last time we discussed it so we'll leave the NIH studies around lactoferrin for you to read:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535893/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676636/
Front page news, right?
Okay…selective immune response becomes really important for our next section.
Our immune system is tasked with detecting and killing cancer. In fact, it uses the same arsenal as any other wayward cell (including virally infected).
A massive dose of oxidative stress (just like chemo and radiation) but specific to the faulty cells only.
Cancerous cells are just like viruses/bacteria in that they need iron for growth.
Hello, lactoferrin:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175311/
Our favorite part (like CBD or Turkey Tail):
Read that back over. It's so critical to everything we're discussing.
The effect depends on whether the cell is healthy…or faulty.
Remember how we said iron controlled the cellular "burn"?
Lactoferrin can fire-hose this burn at faulty cells to cause cell death (called apoptosis).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795860/
Lactoferrin literally has its finger on the trigger (or iron).
The beauty is that it can point directly at cancer cells:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795860/
This makes it an interesting "adjuvant" or add-on player for traditional cancer treatments (always work with your doctor).
https://pubmed.ncbi.nlm.nih.gov/18268518/
We need to add it to our top tools to support cancer success.
Speaking of chemo, let's start to spread our wings a bit. To pain.
Mother Nature likes to multi-task which speaks to all the side effects from common medications (gut and heart dysfunction from COX2 players like NSAIDs).
Not sure why this isn't front page news.
Lactoferrin has a powerful effect on system-wide pain sensitivity.
We're not talking about COX2 or even serotonin (which manages pain sensitivity) or even GABA (nerve and peripheral pain).
We mean the spinal cord. The layered network and pain relay can get "stuck" or even exhausted.
Where opioids operate (till they don't due to brutal tolerance).
Here's an animal pain sensitivity model (don't worry…we'll explain):
https://journals.physiology.org/doi/full/10.1152/ajpregu.00760.2002
It compared lactoferrin (cow) to morphine.
You see "analgesia" or reduced pain sensitivity improve with increasing dosage of lactoferrin. The highest level is just above morphine!
The most important part (for us anyway)...
No tolerance. The body didn't push back against the effect of lactoferrin by reducing natural pain pathways like it does with opioids!
Goodness.
They showed that oral lactoferrin increases NO levels in the spinal cord.
There's both an anti-inflammatory effect (think peripheral pain) and a systemic effect (think fibromyalgia, etc.)
The central effect appears to be around nitrous oxide in the spine which is known to increase our opioid system naturally.
We all know the opioid system for physical pain but keep in mind that it also manages psychological pain!
Come for the back injury, stay for the childhood trauma/neglect or shame.
Goodness…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962838/
We're talking about our fight/flight (hello anxiety, PTSD, ADHD, etc.) system versus our rest/digest system.
And without tolerance.
Check out our review on CBD and pain to look at the players. CBD and lactoferrin could be interesting cohorts against pain.
We're big advocates of addressing the long term effects of early life trauma, infection, and stress.
Lactoferrin may figure into this:
https://pubmed.ncbi.nlm.nih.gov/27763700/
To translate (please!!), lactoferrin and two other milk-based products offset the downregulation of serotonin (5HT1A) and BDNF (our brain's fertilizer) caused by early life stress later in life. This is directly tied to EVERY mental health issue out there.
Learn more about early trauma and mental health. But we all have perfect childhoods (and 3rd trimesters), right?
Let's now go south…to the Gut!
This is so fascinating…we'll use the gut as an excuse to evaluate lactoferrin's effect on the entire metabolism complex.
People…this may be it for all things health.
So we don't get lost in the weeds, let's just highlight a few items:
Speed round!
This may be a key to autoimmune and many of the most brutal diseases you want to avoid. When bacteria and microbes escape across our gut barrier, only bad things can happen.
Lactoferrin is all over this defense:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337092/
A study looked at the effects after a massive bowel surgery:
https://pubmed.ncbi.nlm.nih.gov/24830343/
Learn why this is so important at our gut barrier review.
Lactoferrin will attack hostile bacteria…but what about our friendly ones…the microbiome that practically functions as another organ?
Lactoferrin is able to target pathogenic or "bad" bacteria while supporting the good guys.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801499/
In fact, a big reason lactoferrin is so present in breast milk is to "guide" the nascent bacteria zoo being established.
https://www.jpeds.com/article/S0022-3476(16)00295-X/fulltext
And less of the bad:
What about a gut microbiome wrecked..say by antibiotics?
https://pubmed.ncbi.nlm.nih.gov/35545893/
This should affect gut inflammation states, right?
https://www.frontiersin.org/articles/10.3389/fnut.2021.759507/full
Accumulating indeed. That's a who's who of gut inflammation.
In fact, they're using lactoferrin levels in stool samples to determine IBD/IBS status.
Check out the review on gut inflammation.
Let's zoom out a bit.
We could write a whole review on this but we'll hit the highlights.
https://pubmed.ncbi.nlm.nih.gov/35477124/
https://cdnsciencepub.com/doi/10.1139/bcb-2016-0082
Okay…so blunting glucose spikes and stimulating GLP-1, the pathway behind the blockbuster drug $30K Ozempic (which may push too hard…tolerance).
A measure of sugar damage to the blood.
https://www.researchgate.net/publication/329410858
https://pubs.rsc.org/en/content/articlelanding/2019/fo/c9fo01616c
Fine. What about homocysteine?
Lump in Apoe-B.
Does weight get affected?
https://pubmed.ncbi.nlm.nih.gov/20691130/
Mice study:
https://www.sciencedirect.com/science/article/pii/S1756464611000727
Most of this "operation" above is carried out in the liver. So…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016362/
Covered triglycerides there as well. It's a twofer.
The entire metabolic complex is affected. The big push right now is that metabolism is the root of all evil (or good). Check out "Brain Energy" by Chris Palmer as an example in terms of mental health.
Let's go north…to the brain
Again, we could write forever here but let's zero in on a few key players.
BDNF is our brain's fertilizer. It's literally holding the dam against:
Top two triggers for drug relapse?
It's THE player behind the curtain for all things mental health. Check out our BDNF review.
Is Lactoferrin in play here?
Damage from diabetes as an example:
https://link.springer.com/article/10.1007/s43994-023-00026-9
To whit:
https://www.mdpi.com/2073-4409/10/7/1810
The biggest player for damage is the immune system when out-of-control (remember the bacteria escaping across the gut??)
The major neurodegeneration diseases like Parkinson's and Dementia share something in common.
Excess iron. The immune system and its sentinels in the brain, microglia, may be part of the problem:
https://www.frontiersin.org/articles/10.3389/fncel.2019.00514/full
We did a huge report on Iron Overload and health.
So…more inflammation and more excess iron which we know is toxic.
We should see a reduction of this iron…and a resulting improvement in brain areas?
https://www.sciencedirect.com/science/article/pii/S1756464619306607
Most importantly..
Does lactoferrin even get across the blood brain barrier?
https://pubmed.ncbi.nlm.nih.gov/33977807/
In fact, scientists are looking at lactoferrin to "ferry" other chemicals across the blood brain barrier.
So…how does this really translate?
We're just starting to get research.
BDNF is a huge player. When lactoferrin is withheld from diets in animal models, the result is the equivalent of depression or anxiety:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709556/
Immobility after stress for animals is a sign of…giving up. Look at the effect of lactoferrin!
Then, there's the excess iron issue:
https://pubmed.ncbi.nlm.nih.gov/33977807/
To translate…this is about Lf ability to balance the iron/energy system in the brain.
Check out oxidative stress to learn more.
This brings us to mitochondria, maybe the most important player in they body.
Everything we've discussed above revolves around energy production. After all, iron carries the "fire" (oxygen) and glucose is the energy that runs everything.
This all takes place…in mitochondria. We have a huge review on how to rescue mitochondrial function but lactoferrin must be at play here.
We'll avoid all the way the body uses iron to "kill" both hostile actors and faulty cells. What about mitochondrial function?
In fact, when bacteria do gain entry, it's a slippery slope towards scorched earth by our immune system (sepsis or autoimmune or cytokine storm).
Lactoferrin is the voice of reason:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030479/
If the cell is worth saving, lactoferrin helps to make the call.
Let's look at two energy hunger areas.
First the brain:
https://molpharm.aspetjournals.org/content/molpharm/early/2013/09/27/mol.113.087965.full.pdf
That's Parkinson's folks. Our dopamine neurons are few and precious. Learn more at our dopamine rescue review.
And the heart?
https://pubs.rsc.org/en/content/articlelanding/2021/fo/d0fo03346d/unauth
As we age, our hearts literally grow to make up for lack of efficiency in keeping up with the workload. Check out our mitochondria rescue guide.
So…let's bring this all together!
Our review on blood donation pointed to a key point.
The removal of blood in itself may be a powerful longevity hack due to the removal of excess iron (and broken proteins).
Still early days but…
https://pubmed.ncbi.nlm.nih.gov/34928288/
Always starting with the poor worms:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332254/
They found part of the effect was from better protein balance.
Let's hit some of the longevity highlights:
mTOR - the protein starvation sensor (rapamycin and fasting fame):
https://www.mdpi.com/1420-3049/27/9/2941
SIRT - the cellular shock player (resveratrol, pterostilbene, CBD, etc)
https://pubmed.ncbi.nlm.nih.gov/30534206/
AMPK - metformin, berberine, and fasting
https://pubmed.ncbi.nlm.nih.gov/28867180/
Autophagy is the removal of faulty cells.
So…senescent cells or SASP?
https://www.mdpi.com/1420-3049/27/9/2941
Okay…we waive the white flag!
A few final notes!
What about safety? A few elements that are essential for us:
First, the studies above that mention safety show no issue.
https://www.mdpi.com/1420-3049/27/9/2941
We like seeing Europe's agency weigh in since the US can be…."flexible".
If you're allergic to cow's milk, then look for lactoferrin processed from rice. Lactose intolerance is generally not an issue since there's no lactose present.
As for dosage, there's a wide range:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390755/
Standard doses available through supplements are around 250mg. This matches some of the studies above where different levels were given with increasing effect (at around the 250mg level).
Interestingly, higher levels are used for specific viral infections:
https://www.rxlist.com/lactoferrin/supplements.htm
Work with your doctor…this isn't medical advice or to be used in replacement of standard treatment. It just reflects a high level dose example.
That's 1800 to 3600mg. Again, 250mg over 8 weeks appears to be the best estimate from studies.
Now, there may be an initial window of GI adjustment. This is actually a good thing! Remodeling of the gut microbiome.
This speaks to pathogens, parasites, inflammation, fungi overload, and a general imbalance in the gut. We see this with any substance that shows positive effects in the gut (berberine, CBD isolate, etc.).
It should subside after 3-5 days max. Actually very positive.
What about steroids? We love rapamycin for longevity but not what it does to steroids.
We don't see research where lactoferrin supplementation affects steroidal hormone levels. We do see research where estrogen naturally boosts and manages lactoferrin expression!
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00376/full
You know our thoughts on the power of estradiol!
Beyond the scope of this review, there's interesting research on lactoferrin and pregnancy, fertility, cycle issues, etc.
Now…lactoferrin may cause just better processing of cholesterol and LDL cholesterol is the source of all hormones (via pregnenolone).
So…better processing, better steroidal hormone function:
This is fascinating since steroidal hormone function goes down as we get older See reviews on why this matters across the body and brain:
You can get lactoferrin directly or colostrum. We reached out to one of the big colostrum providers to confirm levels of lactoferrin and they couldn't give a firm answer but estimated at .6%.
That's not much so we stick with straight lactoferrin like this one:
As for longer term use, we do not see signs of tolerance (the enemy!!) with longer term use up to a year from studies.
Remember, the powerful spinal cord opioid effect showed no tolerance whereas morphine nearly lost all effect within 4 days!
This may be the most important piece (along with PQQ, CBD isolate, magnesium, etc.).
Lactoferrin is a fascinating tool for almost every pathway we look at.
This speaks to a very foundational effect.
Our crazy thoughts?
Transferrin, the primary iron manager came on the scene around 580 million years ago
Lf clearly gave mammals an advantage in the age-old war with microbes and then its role expanded from there.
Ultimately, iron and glucose are the stuff of life and lactoferrin directly balances this controlled fire.
Very exciting to have such a hack available down here!
]]>
Okay…you're probably thinking…PQQ. No way I'm taking that.
Granted, it's not gliding off the tongue and not many people know about it…yet.
PQQ is one of our top 3 health hacks (CBD isolate, lactoferrin, and PQQ) available with ridiculous safety.
Our dive into the Top 10 Tools for Mitochondria is what spurred our initial interest and just wait till you see why!
It gets to the root of what drives aging and aging-related diseases!
We'll dive into these areas:
This just scratches the surface.
We can't go into our standard 20 page deep dives but we'll hit the highlights knowing there we can find research on almost every issue you can think of. After all, we're talking about our body's power plants!
Let's get started!
PQQ has been found on asteroids…in fact, it may be part of the alchemy that spread life throughout the universe.
Either way, it was quickly taken up by all life forms starting with microbes like bacteria and fungi.
Almost given vitamin status for humans, there's one thing clear…it's definitely a vitamin for bacteria and that's the fascinating intersection for us.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
When PQQ is depleted, a host of ailments occur across almost all life forms including us.
We can't look at a pathway or issue and not see an improvement from PQQ (assuming there's research).
This is almost unheard of and it's why PQQ is part of our Triumverate (with CBD isolate and lactoferrin).
At its core, PQQ is a critical component for bacteria.
It allows bacteria to process their food (glucose) in anaerobic (no oxygen) environments (hence the asteroid habitat):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
We'll get into specifics below but how can PQQ have such a foundational effect on us as humans?
Hello, mitochondria!
Check out Chris Palmer's book, Brain Energy. Basically, it slow-walks the connections between our energy producers called mitochondria (metabolism) and ALL mental health.
All health really and longevity to boot!
Here's the trick…our mitochondria are actually ancient bacteria that we took hostage (or coaxed??) to make our cellular energy. They power EVERYTHING you're doing.
If they're not running well, we suffer. As we age or with illness, they deteriorate in function. They even have their own DNA separate from ours and it's not great at error-correction (unlike ours).
From a 40,000 foot view, PPQ is a lifeline to our mitochondria:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
That's essentially:
Check out our Mitochondria Rescue review to learn why this is so important.
There are big players in this pathway which will come up so we should introduce them:
PQQ drives all of these for bacteria!
The net effect…
https://www.nature.com/articles/s41514-022-00083-0
Just a head's up…mitochondria are the weakest link for biological function in ALL animals…including us.
This is great and all but how does it actually translate? We're not bacteria. Or are we (health-wise)??
Let's first zero in on the most energy-hungry areas of the body (lots of mitochondria). We'll start up North.
The brain uses 20% of our total body's energy even though it's a fraction of total weight.
Let's zoom through a range of important attributes with PQQ:
Just a sampling if you will!
PQQ and mitochondria decline as we age (more on that later). So…
https://pubmed.ncbi.nlm.nih.gov/34415830/
That's a "randomized, double-blind, placebo-controlled, parallel-group clinical investigation"
What about neurodegenerative diseases?
There's a known issue with mitochondria function (and resulting iron overload) with Parkinson's:
https://www.frontiersin.org/articles/10.3389/fnmol.2021.797833/full
Complex I is the first chain of energy production in mitochondria (like a conveyor belt).
And PQQ?
https://www.sciencedirect.com/science/article/abs/pii/S0304394018306372
Check out our deep dive on Parkinson's and really zoom in on dopamine rescue.
What about dementia?
First, some of the telltale signs of dementia, are the fishing wire-like amyloid beta tendrils:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850417/
In our dementia review, we go deeper into how these are actually immune players.
In mice genetically bread to get their equivalent of Alzheimer's, PQQ, and low dose lithium:
https://pubmed.ncbi.nlm.nih.gov/25018109/
What about TBI?
Resolving the inflammatory firestorm following brain injury is critical and interesting research is looking at PQQ on this front.
First, the technical jargon in how PQQ affects key immune responders to TBI:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303106/
The translation??
This is one of many studies. Let's go broader though.
We have deep dives on facets affected by PQQ which are directly tied to mental health:
Again, Chris Palmer's book puts mental health squarely at the doorstep of mitochondrial function.
So…
https://www.ffhdj.com/index.php/ffhd/article/view/81
Goodness.
We love this study because it also gives us the 8 week marker as a basis and shows no tolerance.
The more interesting piece was its effect on circadian rhythm and sleep:
Cortisol drives our daily cycle (peaks in the morning and drops at night…ideally).
Check out our Sleep Rescue review to understand why this is so important.
Sleep loss looks just like extreme anxiety on MRI scans.
We look forward to much more research but if Chris Palmer is correct, the full spectrum is at play here.
Let's turn to the other energy hungry area…the heart.
Keep in mind that mitochondria process cholesterol into steroidal hormones (see estrogen, progesterone, and testosterone guides).
More importantly, mitochondria are at the heart of…heart failure!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088994/
Which begs the question…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369269/
Front page news, right??
It's a litany of effects with positive outcomes on the heart:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369269/
Goodness…in the live body, PQQ:
The net effect of this "calming" activity?
These factors can prevent mitochondrial dysfunction, thereby reducing cardiac damage caused by pressure overload and preventing the occurrence of CHF.
Just to be clear, CHF is congestive heart failure. Kind of a big deal.
Check out the research on PQQ and heart inflammation from that which can't be named:
https://journals.sagepub.com/doi/full/10.1177/1934578X221080929
Let's head down south.
The bacteria that make up our gut (the microbiome) are all the rage for health these days.
Since PPQ is a bacteria vitamin essentially, what does it do there? Can it drive bad bacteria growth as well?
This is soooo important and one of our favorite studies.
Researchers looked at PQQ supplementation for pigs with e-coli overgrowth:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396494/
Let's break this down because it's too cool.
PQQ given to pigs with e coli overgrowth in their gut:
The last one is critical. PQQ is able to selectively support bacteria that are beneficial to our gut function.
It's hard to really square how it's able to do this other than to suppose that we co-evolved with PQQ over millennium.
The gut barrier is key to auto-immune, heart and brain health, plus system-wide inflammation states!
Check out reviews on gut barrier or gut inflammation to learn why they're so important.
Fine…what about general disease states. We'll pick some big ones.
We've covered some of the leading killers already (heart, dementia, that which can't be named, etc.).
Let's quickly look at:
The big one first.
Mitochondria are literally the band-leaders for all things metabolic. After all, this is the seat of energy and metabolism is how we make/use energy.
So…
Don't get us started!!
PQQ activates AMPK, a key metabolic switch that drives the longevity benefits of metformin, berberine, fasting, etc.
It tightens up the entire metabolic ship!
A fascinating study looked at mice fed a "western diet" and supplemented with PQQ. The effects were long-lived!
https://pubmed.ncbi.nlm.nih.gov/35682720/
Essentially, the offspring saw better liver processing of fats and sugars (triglycerides) from their mother's PQQ!
A net effect was the protection of gut and liver function:
Keep in mind, the liver governs our metabolism to a great extent (fat and sugar processing).
And cholesterol?
https://pubmed.ncbi.nlm.nih.gov/26226960/
Animal studies are starting to look at diabetes directly:
https://pubmed.ncbi.nlm.nih.gov/26343954/
A study looked at fat creating specifically:
https://pubs.acs.org/cms/10.1021/acsfoodscitech.1c00301/asset/images/large/fs1c00301_0007.jpeg
Let's turn to the liver.
How about the most common source of liver dysfunction…alcohol induced cirrhosis.
https://www.sciencedirect.com/science/article/abs/pii/S1359511319312930
Goodness…that's a who's who of bad markers (go down) and good markers (go up).
The glutathione (our primary detox pathway) increase is the big one. See our review on glutathione.
Big shocker…triglycerides and malondialdehyde (a toxic metabolite) both went down.
What about the immune system?
Let's look at a classic example..psoriasis (see our big review here):
https://pubmed.ncbi.nlm.nih.gov/26319019/
Wait…what?
What's fascinating is that PQQ's effect was in modulating key immune inflammatory responders.
What about MS, a disease where the immune system attacks the myelin coating around nerves?
They're literally looking at PQQ to drive myelin growth for repair:
https://pubmed.ncbi.nlm.nih.gov/15915445/
Schwann cells are where myelin is made.
We look forward to more but both immune rebalancing and repair look promising.
On to strokes.
Cut to the chase (since we looked at this with TBI above):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
A big part of the damage that occurs from a stroke is the loss of actual brain mass.
Rats without PQQ supplementation had infarctions across −95 percent of cortices compared to −70 percent in rats pretreated with PQQ.
Let's take a flyer.
The gonads are actually subject to mitochondrial stress due to energy needs and high turnover.
Animal studies are getting interesting.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942821/
And the ovary?
https://www.sciencedirect.com/science/article/abs/pii/S0891584920321079
Okay…we had to just pick a few. Let's turn to cancer.
Our litmus test for the superior hack is something that selectively hurts cancerous cells while supporting healthy cells.
Few and far between (which is why we're huge fans of CBD isolate and lactoferrin).
So…PQQ.
Music to our ears:
https://www.jcancer.org/v05p0609
This is really tricky since the immune system is tasked with detecting and killing cancerous or virally-infected cells.
In fact, mitochondria are at the heart of this process since oxidative stress (controlled by mitochondria) is the preferred weapon.
Chemo and radiation are just massive doses of oxidative stress.
In fact, a study looked at using PQQ to offset the damage of chemo to ovaries:
https://www.frontiersin.org/articles/10.3389/fendo.2022.781404/full
AA is short for Alkylating agents, a cancer fighting tool that causes huge damage to the ovaries.
Check out our big review on CBD and turkey tail for cancer or our top tools for cancer success.
Finally, if it's good for health foundationally, it should be good for aging.
Mitochondrial function is now one of the pillars of longevity research. In fact, they may be the first shoe to drop (bad DNA repair mechanism).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003832/
So…PQQ should have some effect, right?
First, PQQ is all over the popular longevity pathways:
Longevity studies always start with the worms:
https://www.lifeextension.com/magazine/2021/ss/pqq-aging-cells
Fantastic review of "longevity" vitamins here:
https://www.pnas.org/doi/pdf/10.1073/pnas.1809045115
A study looked at age-related deterioration which is usually slowed by AMPK activation and found that one of the key switches that PQQ triggers…is required!
https://www.sciencedirect.com/science/article/pii/S019745801730091X?via%3Dihub
This is exciting. PPGC-1α is directly driven by PQQ!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804159/
Yes, please.
Okay…let's get practical.
The general reading is around 20mg of PQQ for a standard dose.
BioPQQ is processed differently (better) via fermentation as opposed to a pretty harsh chemical process and that's the best approach.
We use this one here:
Research points to PQQ as an adjuvant option with cancer treatment. In fact, research is on protecting healthy tissues (i.e., nerve damage and ovarian function, etc.) with PQQ from treatment.
Work with your doctor of course…with all supplements.
PQQ, along with lactoferrin and CBD isolate make up our Triple Threat for health and longevity.
Very exciting times!
]]>It's rare you come across a behavior or tool that's so powerful across almost every facet of health.
Cold exposure is front and center and but it's too expansive so we're going to zero down into mental health.
Since it's just a tad in focus these days.
There's fascinating new research (led by Chris Palmer's book, Brain Energy) on how metabolism may be a critical piece of what drives mental health, and we have already looked in detail at how early trauma, infection, and stress can hyperactivate immune function and inflammation later in life.
Metabolism and inflammation. Again…right in cold exposure's wheelhouse.
Here are the areas we'll cover:
Let's get started!
All the current longevity tools revolve around energy. The lack-there-of really.
Turns out that there are ancient pathways that turn on when we're faced with hardship:
Cold exposure, as little as 5-10 minutes in 60-degree water is showing fascinating research across almost every pathway looked at!
Huberman labs have a great review, and Wim Hoff is becoming a legend. We also like Dr. Seiger's barrage of research.
We originally came across cold exposure in our dopamine rescue guide but quickly went down the rabbit hole.
You can't find a pathway not positively affected.
Even the new issue around amyloid clotting! See our top 10 for healthy clot removal.
Cold exposure has powerful effects on the following systems which will figure greatly into mental health:
Goodness..just the root of almost every modern health epidemic these days!
So…let's start to look at mental health specifically which rests squarely on everything just listed.
If we had to pick two from the above list, we would focus on steroidal hormones and the immune system (inflammation).
They're all intimately tied (poor metabolism drives inflammation, etc).
We did giant reviews on how early trauma, infection, and stress (even in utero) can drive mental health issues later in life.
This is inflammation at its core!
Since we can go a 1000 different directions, let's take each of those macro improvements and tie them to mental health before digging into some of the weeds below.
CE rebalances metabolic function centered around glucose and fat processing
Dr. Chris Palmer and his new best-selling book, Brain Energy are leading the charge here.
We looked at the whole fat piece (omega 6 versus 3) for brain function and mental health.
The net net:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016046/
Not surprising since the brain is made out of fats primarily and runs on glucose.
We've covered the problem with glucose but it's front and center:
https://www.nature.com/articles/s41598-017-05649-7
Cold exposure has a powerful effect on glucose and fats. Cold exposure tricks the body into thinking it's in extreme peril!
The body immediately sucks glucose up into muscle to be ready for action.
The impact on insulin and lipids (fats) is equally powerful.
A great deal of this is tied to cold exposure's effect on fat. Let's go there now!
Babies can't shiver. So to keep warm, they have large deposits of brown fat. Unlike 'white" fat…the one we're very familiar with which is primarily a means of storage, brown fat is metabolically active.
It actually burns energy! The "brown" color is from higher levels of mitochondria, the power plants of our cells, in brown fat.
As we gain the shiver response, we lose brown fat (or most of it). Cold exposure can actually convert white to brown (or beige) fat with time!
This increases metabolism and energy sources for all cells including your brain!
Now…follow this as it gets really interesting.
One of many effects from cold exposure is a significant boost to a pathway called PGC-1α, a key player in creating new mitochondria (the "browning" process of fat).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545200/
Okay...so what?
https://pubmed.ncbi.nlm.nih.gov/35011673/
This gets back to the Brain Energy book thesis. Brain energy is the key to healthy function.
If you read our review of depression, you see a form of atrophy…a disintegration of brain areas.
And PGC-1a??
https://pubmed.ncbi.nlm.nih.gov/35011673/
Goodness…synaptogenesis…making new connections is depression's kryptonite!
We'll touch base on the brain's fertilizer, BDNF below but it's how CBD, psilocybin, exercise, and SSRIs (till tolerance build up) have any impact!
Let's dive a little deeper into the brain energy aspect!
Mitochondrial biogenesis.
That's the technical term for making new cellular power plants, and it's a critical nexus between mental health and cold exposure.
Remember that the "brown" in brown fat is from the density of mitochondria (technically, the iron content in them).
First, newer research is really pointing to energy deficiencies in the brain and pretty much every mental health issue out there:
https://www.frontiersin.org/articles/10.3389/fpsyt.2021.546801/
You have the most common issue (depression) and a key development disease (bipolar).
Here's where it gets interesting (to us, anyway).
Early trauma, stress, and infection can affect mitochondria function (and mental health) later in life!:
https://pubmed.ncbi.nlm.nih.gov/33484871/
Oxidative stress (the damage from oxygen) in the brain is a key link between both.
In driving more energy production (mitochondria), cold exposure also ramps up the protection and waste removal side (oxidative stress):
https://link.springer.com/article/10.1007/s11055-019-00735-x
Goodness…cold is stress-proofing the brain at the cellular level!
PGC-1α from above is just one key player.
It even goes to glutathione, our key detox and antioxidant in the body and brain:
https://academic.oup.com/qjmed/article/92/4/193/1586500
See more on glutathione for anxiety.
Let's turn to inflammation in the brain!
The new research around mental health really falls squarely in the immune system and inflammatory states.
This is the early trauma, infection, and stress piece which gets marked up into our epigenome…potentially for life!
Let's drop the hammer:
https://www.sciencedirect.com/science/article/pii/S1550413121004800
Goodness…" immunologic reprogramming".
Turns out that there's a competition between cold exposure modifications and…hyperactive immune responses.
The body can't fight cold AND fight itself (via the immune system) at the same time. Too costly to do both.
We have big reviews on neuroinflammation or editing immune system markups.
For long term healing, this is the key and cold exposure is a powerful tool!
One note…proper immune function is required to detect and kill wayward cells (cancer or virally infected, etc).
Here's the beauty..cold exposure actually has powerful anti-cancer effects which reflect proper immune response!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211456/
So…cold exposure boosts immunity when needed (cancer) but calms it when needed (autoimmune).
It "modulates" it! The Holy Grail (see medicinal mushrooms).
Alright. Those are broad strokes. Let's zero into discreet pathways!
We'll start with a cascade of powerful players.
This is really the monster player with cold. For good reason.
The brain thinks we're in impending danger. It doesn't know we're going to hop out after a few minutes and an entire cavalry cascade occurs.
The front and center is the fight or flight side of the autonomic nervous system.
The heavy hitters here are adrenaline (norepinephrine) and as a result…dopamine.
This makes sense as dopamine is about zeroing our focus on survival-related targets and movement!
Get out!
We think of dopamine as a pleasure player, but that's not really true. It's more of a reward driver.
Here's the fascinating piece…low dopamine feels really really bad (depression), and no dopamine feels…like crushing despair. Dr. Huberman's review on dopamine goes into that. Must listen.
We have massive reviews on dopamine and dopamine rescue (it's under assault from every corner these days).
Dopamine is tricky though…if you spike it, it will subsequently drop by an equal or greater amount!
Strange see-saw relationship with pain (physical and emotional).
Cold exposure is one of the few ways you can raise the baseline or tonic dopamine levels…for long periods of time!
The effects are powerful with cold exposure:
https://link.springer.com/article/10.1007/s004210050065
That's 2 ½ times more than sex (a huge driver of dopamine) and even more than nicotine. Both of which have "refractory" or rebound periods.
There are powerful connections between dopamine and depression, bipolar, schizophrenia (literally a disease of dopamine mismatch), and more.
Cold exposure is one of the few ways we can increase it without the pushback that nature built into the pain/pleasure system.
It's intimately tied to other powerful neurotransmitters including our next one.
Serotonin is our "feel right in our skin" player as manager of ALL human behavior but there's a side hustle.
Serotonin is a primary stress response buffer!
The brain uses it to temper your mood, energy, and pain sensitivity in times when we're in jeopardy (stress).
That's why your mood drops when you're sick…literally, the conversion of tryptophan to serotonin is turned down.
The relationship with cold exposure is a curious one.
First, serotonin will drop during the cold exposure activity itself. Makes sense…intense stress!
But…cold exposure has a powerful effect on inflammation and serotonin also gets it signal from the immune system.
Viruses and bacteria make more of themselves from tryptophan so the body will squash conversion to starve them out (which starves out our serotonin).
Inflammation is the "signal" from the immune system to serotonin, and when it drops, serotonin gets the all clear!
https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(21)00480-0
That's the whole autoimmune trade-off from above.
Less brain inflammation (or gut) means more serotonin longer term.
One note…early trauma, infection, or stress (even in utero) can downregulate serotonin throughout life by this very mechanism. Increases systemic inflammation (hyperactive immune system)!
Right that ship first! Check out our review on serotonin or why the immune system is the future of mental health.
One key result from serotonin is your new best friend for mental health. BDNF.
BDNF is the secret superstar of mental health and addiction.
It's the brain's fertilizer and in daily opposition to:
Goodness…outgunned in many cases.
So…cold exposure's effect there since it's a downstream result of serotonin function?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768886/
Okay…we need to introduce Ucp-1. Uncoupling protein 1.
Basically, it takes some of the cellular energy production offline to leak out heat. That's the primary mechanism in brown fat to warm us back up.
This effect of UCP1 and BDNF is more fascinating!
Essentially, the body is detecting stress/damage (cold storm) and calling in the repair crews.
Check out our review on brain repair.
BDNF is the star behind:
Two biggest triggers for addiction relapse??:
Now…a very curious missing player with cold exposure.
We talked a lot about the "stress" of cold exposure.
This should be bad, right? After all, serotonin gets exhausted by stress.
Here's the fascinating piece….cold exposure brings the positive side of stress (adrenaline and dopamine) but not the negative (cortisol).
Cortisol is our primary stress hormone. Cortisol's effect on mental health is well-established but the duration and expectation matter.
So…cold exposure (without hypothermia of course):
That's a great review by the way.
This is called "eustress". Good stress (like exercise). By constantly priming this autonomic system, you're building resilience as well.
Let's turn to our favorite subject…steroidal hormones.
In our rewriting your mental health past, we focused on two elements:
People…this is IT for mental health!
Check out the reviews on each as they directly drive mental health.
Too bad Progesterone and Testosterone drop around 1% from age 20 and Estrogen goes off a cliff late 40s for women.
We took a look at rapamycin for longevity (more at our health hacks page) but there's a downside there we didn't like.
A drop in steroidal hormones. Makes sense…in times of simulated famine, not a great time to reproduce!
This may be cold exposure's secret weapon!
It can actually significantly increase steroidal hormones across the entire gamut…even LH (luteinizing hormone) which drops when you supplement with HRT as a pushback.
There's a good walkthrough here:
https://www.morozkoforge.com/post/ice-bath-prostate-testosterone
We need better research.
The timing matters (cold after and not before exercise is best).
What on earth is going on here? We mentioned how famine was bad for steroids…why would the perceived "danger" of cold have the opposite effect?
There's a fascinating interplay between brown fat and steroidal hormones.
To wit…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768886/
Trophic means pro-growth. More activity.
LH is the primary "initiator" of steroidal hormone production in the gonads. The signal to make more (estradiol, testosterone).
Why would nature tie "cold" to steroidal hormones aside from the growth/repair side (similar to BDNF)?
Our theory??
There's actually a fascinating "annual" cycle for steroids. They peak late fall when the temperature drops. The evolutionary "goal" is to have babies late summer and the 3rd trimester (key for brain development, etc) during summer when times are good.
Viruses peak during the winter (their shell literally melts with cold weather) so best to avoid all this when expecting towards the final 3rd of pregnancy.
Either way, there's an ancient connection between temperature and steroids.
One we can ride back into good mental health.
Look at the reviews to really see how important they are:
Let's really zero in on the brain inflammation piece since it's front and center with mental health.
We touched on this above but let's dive in since the immune system is the future of mental health.
Since brown fat is the key driver of activity from cold exposure, let's start there.
It turns out that brown fat is incredibly anti-inflammatory while white fat can be very inflammatory. Systemically!
In fact, a study transferred brown fat to mice with autoimmune arthritis:
https://www.nature.com/articles/s41598-020-68749-x
Goodness..that's a laundry list of inflammatory agents.
In fact, it reflects a T1 setting in the immune system which is directly linked to every mental health issue out there.
See our neuroinflammation review to learn more.
In fact…our white fat may be part of this one-way inflammaging:
https://www.nature.com/articles/s41598-020-68749-x
Why this matters for mental health?
https://www.sciencedirect.com/science/article/pii/S2666354620300107
Wait…TNF-a and IL6 were directly reduced by brown fat (and therefore cold exposure).
Here's the fascinating piece (to us anyway)....early life stress can alter fat distribution later in life!
https://pubmed.ncbi.nlm.nih.gov/28088658/
ES is early life stress. WSD is western style diet (see our fats review).
More white fat = more inflammation = higher mental health risks!
Okay..lots of pathways and we could go on. Let's dive into key issues.
We have a massive review on anxiety.
At its heart, anxiety is failure of stress response (GABA, then serotonin, then anandamide) combined with brain areas leaning too hard on fear/vigilance.
We've covered many of these players above but how about a direct study?
Okay...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734249/
HDRS is a standard depression test. HARS is a standard anxiety test.
50% drop! That's….well phenomenal.
That was after 3 weeks and the "remodeling" from cold exposure can take at least 30 days. That's how long it takes for receptors in the above pathways to come back online.
After all, DNA has to be turned back on! BDNF alone takes time since it's literally building new brain connections.
What about anxiety's partner in crime, depression?
Big review on depression here but it can best be seen as a disintegration of brain areas and activity from the assault of hormone loss, trauma, stress, infection, and other back actors.
Longer term, anxiety can cause depression from the sheer wear and tear.
New studies are starting to bare out the results of cold exposure:
https://pubmed.ncbi.nlm.nih.gov/17993252/
Look at the results of a standard mood test (POMS) of just one exposure!
https://onlinelibrary.wiley.com/doi/full/10.1002/lim2.53
This test measures both positive and negative mood qualities. Look at the results from one cold exposure:
Goodness. Good luck getting that with SSRIs (see the problem with SSRIs).
Okay…a quick speed round of mental health
We need better research.
All mental health issues have shared attributes:
We've seen above cold exposure affects each of these!
There's plenty of anecdotal info on various issues but we need more research. We expect it to follow suit with anxiety and depression and look forward to new data.
We've avoided one key area…maybe THE key area.
Let's go to the autonomic nervous system.
We're going to zero in on the vagus nerve, the hub between our two brains (gut and in the head).
One, is a key internal sensor, and the other, an external sensor.
Big review on supporting the vagus nerve but a primary role of it is to release acetylcholine.
That's the opposing force to adrenaline…it's our "calm and focused" player.
Seem relevant for mental health? It's a powerhouse for stress response. Just think what adrenaline feels like!! It's the opposite. But alert.
So…when we get into cold, adrenaline spikes (with dopamine) by default.
The body's a funny thing. If you spike any given pathway, it will actually exhaust a bit.
You see this with tolerance and every drug or most medications.
So what happens after the "cold shock" in this background system?
https://pubmed.ncbi.nlm.nih.gov/11447037/
Right the ship! A spike in adrenaline will lead to a rebound increase in acetylcholine.
Just a head's up…this system is critical to ADHD, PTSD, anxiety, and more.
Okay…now get ready for this.
First….a basic definition:
https://my.clevelandclinic.org/health/body/23266-parasympathetic-nervous-system-psns
Safe and relaxed indeed.
Now..the kicker…
https://pubmed.ncbi.nlm.nih.gov/18785356/
Let's translate that because it's too cool!
THIS is the key to just about every mental health issue in a very powerful player (autonomic nervous system) that we have very little control over.
Panic attacks. Anxiety. Mania. ADHD. Pyschotic breaks.
We're slowly building resilience into our stress response system!
Check out other ways to support the vagus nerve but let's look at protection in the brain.
After a traumatic brain injury, hospitals will literally surround the skull with ice.
You may recognize some of these players from above:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913523/
In fact, those are all present in every mental health issue you research.
We could get lost in the weeds but let's look at one exciting pathway.
FGF21. Goodness…a droid name?
No…it's a key player in breaking down amyloid plaques. Check our review of amyloid clot pathways.
FGF21 is a superstar in brain protection from everything we just listed!
https://www.sciencedirect.com/science/article/pii/S0753332220306326
Goodness. Brain Inflammation. Mitochondrial dysfunction. Oxidative stress.
And cold exposure???
https://pubmed.ncbi.nlm.nih.gov/23150685/
Makes sense…the body thinks its in peril…protect the vital cargo (brain).
Let's wrap up with the age-old (about 8 billion years actually) battle.
Let's introduce the opponents.
In this corner, you have our old "reptilian" brain player. Evolutionarily ancient and pretty similar to our animal brethren.
This is where dopamine drives impulse and survivability.
The new player is the pre-frontal cortex, the kid on the block where humans picked the lucky ticket.
It's what makes you…YOU! Higher executive function. Planning. Thinking. The human stuff.
Here's the fascinating piece for mental health.
We have two brains.
Mental health issues arise when the rational (adult) actor (pre-frontal cortex) is outgunned by our more child-like brain area (amgydala, striatum, etc).
As a simple example, anxiety occurs when the fear signal is too strong or the push back is outgunned.
The so-called "anxiety circuit".
In the case of depression, the prefrontal cortex just isn't running "hot" enough.
Why bring all this up with cold exposure?
Let's walk through it.
When you first feel the cold water, the "reptilian" brain is saying "Get the HELL out. NOW!!!"
Impulse. Impulse. Impulse. Pleasure seeking, pain avoiding.
Now…the only thing keeping you from darting out is…the prefrontal cortex.
You are "willing" yourself to stay in because you know you're buying future pleasure/calm/balance on credit!
However much pain you feel…will result in equal and even greater good feelings later.
That's rational. That's prefrontal cortex.
Everytime you do this, you're strengthening this area of the brain. You're building resilience.
It's very similar to mindful meditation where the action strengthens key pathways (hint hint…vagus nerve).
Working out is exercise for the body. Cold exposure is exercise for resilience.
You get the picture. Work with your doctor. Listen to the Huberman podcast on various protocols to stay safe.
Be well. Cold exposure is a hack we have down here so take advantage of it.
Top 10 tips for mitochondria support
CBD and Anxiety - the Ridiculous Guide
]]>
It's everywhere. Stress!
The pandemic didn't help much, and now inflation is spiraling. Out of the frying pan…
Our basic system for coping with stress is severely stretched and just beyond the edges, you have anxiety, depression, and panic attacks. Or worse.
In fact, the two most common triggers for drug relapse are:
Wait what? The first is a no-brainer but the second one is just a bunch of letters.
Don't worry, we're going to cover that because it's critical for long term stress smack-down action.
In fact, there's a slew of tricks to keep stress under wraps, and we'll cover them here:
Let's get started! So many goodies here.
First, understand that stress is just a signal from the brain:
It keeps us moving forward and out of harm's way. The problem is chronic or acute (very intense) stress.
Our natural systems can be outgunned and anxiety is the actual correct response.
Something is not right here…CHANGE!
Let's introduce both sides of the field so we can look at actual tools based on research.
On the bad guy side:
Now..in a normal situation, these players should all calm down and come back to baseline.
You can't STAY at defcon1 forever without burning out the circuitry.
Who's actually in charge of the pushback?
That's the stressful playing field (for the most part with stragglers and weird short-stops here and there).
A few key notes before we begin.
The standard meds to hit these players give us a clue (and a warning):
So…you see we're on the right track although we need come at it from a different angle.
As for the good-guy side, there are lots of supposed supplements to boost GABA (l-theanine, GABA, gabapentin, etc.) and serotonin (5htp, SAMe, etc.) but there's the same issue.
Tolerance is THE enemy. Basically, anything that hits a pathway too hard will cause your brain to push back and actually REDUCE natural levels.
It's really the kryptonite to most meds/supplements when it comes to stress.
Sure…alcohol or cannabis might temporarily feel good when stressed…but you're going to pay!
See the alcohol or cannabis review to learn more.
We need tools that DON'T build tolerance or cause a rebound in the very players we're trying to support.
Hello, Top 10 List!
Let's get started before we absolutely lose our #*%^.
I can't say enough about mag. In fact, we have a massive review of mag and stress, sleep, and pain here.
Mag is our natural calming agent in the body and brain, and it's significantly handicapped these days.
We use to get our mag from the soil-to-the-food conveyor belt (essentially soil bacteria and fungi) but good luck finding that with Arby's new menu.
Many people are deficient, and that's bad news since mag is our natural stress response buffer:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761127/
So get this…mag keeps glutamate (gas pedal) at bay and supports GABA and serotonin function but when we're stressed, our body dumps it out via urine!
Viscous cycle indeed.
Magnesium glycinate or threonate passes the blood/brain barrier best. Most others don't (we learned the hard way from migraines).
We take 3 x 100mg daily or as needed (great in the middle of the night).
Mag is a natural laxative so you'll know when you have too much.
Otherwise, it's our best friend in times of stress. Check out the full review of magnesium here. We use this one here.
It's really our metallic shield against stress in the nervous system!
Next up…the balancing actor.
We actually have a system that is tasked with righting the ship after stressful situations.
It's called the endocannabinoid system where CBD and THC work.
The issue with THC is that it hits too hard and for too long (imitating anandamide) which causes the body to "exhaust" these feel good pathways after stress or even reduce them longer term.
Wrong direction. A stress "hangover."
CBD isolate on the other hand supports this system…when low! When exhausted.
Technically it's called an allosteric positive modulator but if you're not up on your Klingon…it's a feedback mechanism to support when running too low.
Since this system is tied into every other system, you see widespread effects:
Check out our CBD and stress response or better yet…CBD and public speaking study…for people with DIAGNOSED social anxiety!
Just one (of 100's studies) example with serotonin, our master stress response manager:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
Look Ma! No tolerance! And no serotonin syndrome.
See why we geek out?
Hold under the tongue for up to 60 seconds to speed/boost availability. Generally, 100mg-300mg daily or as needed matches the research. We use this one.
Next up, GABA's ugly cousin. Unless you're into calm and sleep.
Big review on glycine here but let's hit the highlights.
Glycine is an amino acid…a simple protein with big effects on the brain and nervous system.
Where GABA operates in the brain, glycine shares duties with the brain stem and the rest of the nervous system.
This speaks directly to the "bodily" sensations of stress driven by adrenaline. Things you can't control like a heartbeat or blood pressure, etc. Signals that go from body to brain and cause…alarm!
Glycine's role there:
https://hospitalnews.com/nutritional-treatments-to-combat-anxiety-disorders/
Ah-ha! NE is norepinephrine (precursor to adrenaline). This is huge for panic. Anxiety.
"Over arousal" sound familiar?
We need to short-circuit this adrenaline feedback loop, and glycine is a key tool.
Great before sleep but also during times of intense stress (you feel frazzled).
3-5K glycine matches research, and we use this one here.
Now…you're going to hate us for the next one.
We just wrapped a massive review on rescuing dopamine in which we were just mesmerized by the effects of cold exposure.
There's almost no tool like it!
When you expose yourself to cold (safely - see Huberman labs), there's a fascinating hack that goes on with stress response.
When exposed to cold, your body releases adrenaline (expected…it's COLD!)....but not…cortisol!
It's a GOOD kind of stress. Called eustress...not distress. More importantly, you're literally buying future calm and pleasure by enduring the pain and cold.
Don't get mad at us…we didn't wire this evolutionary yin-yang into life.
But we'll use it!
This is ancient hardware we're hacking into!
You're slowly building your stress response with a GOOD flavor of stress. One our body has been programmed to deal with for…millions of years.
10 minutes in 60 degree water (a cold bath) can elicit most of the benefits. Take into account your health and work with a doctor/naturopath.
Check out our dopamine rescue if you need some motivation to deal with the cold.
You'll never look back once you incorporate this activity and stress will slowly fade into the ether.
Compared to fear of freezing, that exam or meeting is nothing to our basic programming!
We're going to do a massive review of cold exposure and mental health shortly.
One weird quirk of cold exposure is a pretty big increase in steroidal hormones. A bonus.
Let's go there now.
Estrogen, progesterone, and testosterone are absolute monsters in your stress response system.
Too bad progesterone and testosterone are dropping around 1% from age 20 and Estrogen goes off a cliff late 40s.
We learned this the hard way (our brutal perimenopause story).
We have big reviews but the key takeaways:
Goodness… the here and now (GABA) stress buffer as well as our long term manager (serotonin).
Check out the reviews…that's just the start of it since every cell in your body has receptors for all three.
Reproduction indeed.
Keep in mind that we're swimming in environmental hormone disrupters (plastics, cosmetics, food additives, omega 6 - seed oils, etc.)
Testosterone levels have dropped significantly across ALL age bands from 20 years ago. Estrogen is walloping progesterone when it should exist in balance.
Get your levels checked. The cold exposure trick above is one of a few ways to really support these key players.
Let's turn to the gut (where steroidal hormones also work).
The wild west of health is in the gut. Probiotics and fungi….most of which we know very little about.
A few stars are emerging though that we can take advantage of to support our gut which in turn, tells our brain how to feel!
Don't believe us??
https://www.nature.com/articles/s41386-020-0732-x
Translation: by messing with gut fats and bacteria, researchers can change the brain's response to social stress.
What??? That's just the tip of the iceberg. They can transfer fecal bacteria from anxious mice to non-anxious mice…and make them anxious. Or display Parkinson's. Or Depression. On and on and on. And vice versa!
Akkermania M is one such player (of many to come) we can look at now.
In fact, a study looked at supporting akkermansia for Chinese students under intense stress from the notorious college exams:
https://www.hindawi.com/journals/dm/2021/5597401/
Reduced anxiety and depression from the stress-induced situation.
Or in mice:
https://www.nature.com/articles/s41598-019-40140-5
How do we boost akkermansia? A few ways:
Check out our big review on berberine. We use this one here.
Let's now go north to the lungs.
Wim Hof of cold exposure fame also spends quite a bit of time on breathing.
How we breathe is a powerful signal to the brain in times of stress….the communication is bi-directional.
The brain is looking for signs of distress in the body (heart racing, vasodilation, faster breathing, etc.) resulting from stress.
You can 'trick" this flow of information by directly focusing on the breath.
There are many "practices" but we'll focus on a well-tread one and explain why the out-breath length is so important for stress.
4-6-8 is simple and effective:
The focus should be on really expanding the diaphragm (just below your breastplate…think stomach) and breathing OUT as long as possible.
First, the diaphragm (expand stomach):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455070/
The diaphragm breathing group saw cortisol (primary stress hormone) drop…significantly! You're mechanically pushing on the vagus nerve, our seat of "Rest and Digest".
Then the out breathe:
This is ancient machinery we can hack.
Breathing in…harder and faster is a trigger for fight or flight. In fact, in times of stress, hyperventilation or even holding breaths (or very shallow breathing) can take over…automatically.
You can't SIGH when stressed! Or can you? If you force this action (long outbreath), you're tricking the brain into thinking everything's chill.
We'll talk about where this happens below (vagus nerve) but just know that our breathing is both a result and driver (when we force it) of the stress response.
Let's turn to some unsung heroes.
Vitamin B's seem so passe in light of everything we've talked about above.
This couldn't be further from the truth!
In fact, B vitamins are key players that exhaust stress.
So…top level:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770181/
A 23% reduction in stress across a list of studies.
A range of studies dive deeper into the effects:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847740/
Now combine this with MTRR and MTHFR, genes that govern B12 and folate function for which, many people have variants which result in reduced function.
Folic acid actually competes with folate for these people! Methyl versions of B vitamins are very important here.
That's just a few people right?
Just around 40% of the population. Goodness.
B vitamins are critical to a range of processes but front and center is managing cortisol levels.
and (wait for it)...GABA!
https://www.livestrong.com/article/497824-vitamins-that-help-with-cortisol/
We did a whole review on Vitamin B's and mental health.
Choline happens to be a B vitamin and it's critically tied to our next section.
Let's turn to the very fascinating Vagus Nerve!
Right below your breastplate (hint hint from the expanded breathing and diaphragm above), you have a powerful hub between your gut brain and brain.
It's called the Wanderer since it branches out across your torso and organs.
Our focus is on it's primary chemical product…acetylcholine.
The "calm and focused" neurotransmitter!
Sounds like something we want to know?
We have giant reviews on the Vagus nerve and acetylcholine separately but this is half of the "background" stress response unit…the autonomic nervous system.
You know when your heart races, pulse quickens, sweaty palms, eyes dilate, etc.??
That part!!
The vagus nerve directly ties into the heart and lungs to manage these responses whether we like it or not.
But…we can affect the vagus nerve and support acetylcholine (besides nicotine which mimics its shape chemically).
Check out the full review but here are some key tips:
Gratitude. Saying "thank you". Appreciation.
Hello, Gratitude practices. Hello, mindful meditation.
Support this nerve and watch your stress response improve not only in a jam…but long term.
Let's turn to fat.
We did a massive review on the great Fats con game.
How our healthy omega 3's have slowly been switched out for very cheap, factory fat (seed oils) and all that comes with that.
We could go into brain inflammation, oxidative stress, steroidal hormone reduction, and much more but let's zoom out to 40,000 feet!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510994/
Goodness. Can we just drop the mic now?
Newer studies are getting even more sophisticated!
We'll walk through this one:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510994/
Basically, stress will actually age you. Reduce telomere lengths, the shoe-lace-like binding of your genes which signal aging.
Cortisol and even a key inflammatory agent called IL6 all get ramped up.
Omega 3's blunted these effects following stress!
And during the time of the stressor:
People…Omega 3's are a key stress response buffer.
High quality fish oil screened for contaminants is available…now! We use this one.
Okay…that's a wrap but before heading off, we have deep dives into related topics:
]]>There's fascinating new research in the longevity space around iron.
Specifically how iron stores build up in the body as we age and cause a range of issues. Maybe aging itself!
That's part of the basis behind the whole blood donation craze and a big reason why women fare better than men (till menopause kicks in).
We'll look at the whole iron question for health and how CBD affects it with these topics:
Let's get started!
First, what's the connection between iron levels and aging?
Just this…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544343/
In fact, there's a range of age-related diseases that show hallmarks of elevated iron including Parkinson's, Dementia, and more.
As for the heart???
https://www.mayoclinic.org/diseases-conditions/hemochromatosis/symptoms-causes/syc-20351443
As we get older, our production of heme decreases and this leads to iron accumulation as well as a host of other damaging agents.
This is partially behind the new research around blood donations and longevity effects.
To avoid the "healthy people donate blood" bias, researchers looked at mice. The effects were profound across multiple pathways.
The net net..
https://www.lifespan.io/news/blood-donation-slows-skin-aging-in-mice/
Goodness.
That's:
So back to people even with adjustment for other healthy attributes...
https://pubmed.ncbi.nlm.nih.gov/26098293/
It was 18% total and 7.5% after balancing other health attributes.
From donating blood!!
So…are there ways to protect against excess iron?
We know that CBD supports our primary balancing system called the endocannabinoid system.
What about balancing iron?
A fascinating study broke it wide open with brain iron overload (extremely destructive).
Iron in the brain can lead to a range of issues with the mitochondria, and our cellular powerplants (more on mitochondria).
CBD's effects...
https://www.sciencedirect.com/science/article/pii/S0361923017303714
mtDNA is short for the DNA that makes our mitochondria. Essentially, excess iron is sabotaging our entire energy complex.
The study above showed how glutathione goes up after blood donations which makes sense.
Glutathione is our primary detox agent, and if mitochondria are malfunctioning, the glut will be eaten up!
CBD directly impacted the iron-management system:
https://www.sciencedirect.com/science/article/pii/S0361923017303714
As a reminder:
In fact, iron excess will lead to cell death…apoptosis.
And CBD's effect??
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120904/
Keep in mind that loss of these neurons is key to dementia, Parkinson's, and just plain age-related mental reduction.
This is quite exciting, and we look forward to more research.
Learn all about how the mitochondria are becoming the stars in longevity and mental health (see book, Brain Energy).
So…what about practical questions around CBD support?
We don't have hard research on how much CBD to support this iron damage pushback.
Peak levels would be 300mg which matches maximum neurogenesis (brain repair…the opposite of apoptosis from above).
Our estimate would be from 100mg to 300mg based on this ceiling.
See reviews on issues tied to iron overload:
What about the type of CBD?
We want zero THC since it can interfere with mitochondrial function (more on how CBD protects from THC).
Mitochondria may be at the heart of this whole effect since iron is used by them for energy production. Iron is what makes brown fat (increase in mitochondria)..."brown"!
We also want the basic requirements for CBD:
These are mandatory…especially the 3rd party testing part.
Full spectrum can cause a histamine response which is just the forward guard of the immune system's inflammatory response. That's going in the wrong direction.
CBD isolate has actually been shown to calm histamine and mast cell response (see CBD and histamine).
Tumeric, quercetin, green tea, and resveratrol are other iron "chelaters" or removers with strong safety profiles.
These all have something in common with CBD…
They are players in the powerful SIRT pathway!
Why does that matter? Just this…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373873/
So…SIRT2 is tasked with balancing iron levels and function.
One problem.
Keeping iron range-bound is appearing to be an exciting tool for both longevity and general health itself with big ramifications in the brain as we age!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>Research keeps coming back around.
To the alien interlopers we hijacked roughly 1.5 billion years ago. Mitochondria.
So much more than JUST the power plants for every thing you do.
Brain Energy - the revolutionary new book on mental health and metabolism lands squarely at the footstep of these ancient bacteria.
Longevity is quickly being routed here…from every angle.
Just a few quick notes from the longevity frontier:
The mental health effects are just the canary in the coal mine since those effects are more noticeable.
Same for heart, muscle, bone, organs, etc.
So…how can we support mitochondria…naturally?
Let's go there!
A quick intro the fascinating worker bees in your body:
Let's get started…first, an introduction is due!
We all know the staid description...
Mitochondria produce the energy in our cells.
That's just the start! Energy is literally the stuff of life so they also have powerful sensing and signaling effects within the cell and across the body.
Newer research is really showing mitochondria at the crux of:
We just named 80% of the TV ads for medications.
And cancer?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460667/
To translate…when mitochondria break, the whole cancer detection and removal system goes offline.
We can quickly get lost in the weeds so lets focus on how to support mitochondria function along these lines:
This is the trifecta of mitochondria function.
One important note…the whole "antioxidant" push may not be the entire story.
Oxidative stress is a signal to the mito machine to clean out old copies and make new ones. Equivalent of the order down to the boiler room for more power! Or "I need more power, Scotty" for Star Trek fans.
Oxidative stress is also the bullet the immune system uses to kill faulty cells (and mitochondria) including cancer! There's a balance.
Studies have shown that antioxidant supplementation actually COUNTERED the benefits of exercise:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697466/
Goodness. We'll have to shape our list based on this new respect for oxidative stress (within bounds). Onward!
There's just no getting around it. Exercise directly drives mitochondria function.
Makes sense. Mitochondria make energy. Exercise is an extremely high energy hog.
The body will respond accordingly. Across all three requirements above!:
https://www.frontiersin.org/articles/10.3389/fphys.2021.660068/full
Exercise drives AMPK, one of the current frontrunners for longevity (metformin, berberine, etc). We have a huge review on AMPK here.
It's as close to a silver bullet as have.
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP278853
Look at the relationship to exercise and/or age. An active 70 year old has the mitochondrial function of say a 50 year old judging by the curve.
Let's introduce a key pathway we want to target: PGC-1α
PGC-1α is the band leader of mitochondrial function and exercise's role is many and strong:
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP278853
Remember how we said that antioxidants may be not be the magic pill once pushed?
A slew of pathways are initiatied to keep everything in order including UPR and PINK1 (removes faulty mitochondria).
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP278853
ROS…reactive oxygen species. Antioxidants are neutralizing ROS but taking away the critical signal to turn on an entire complex of mito management paths.
Hence the studies above where antioxidants can neutralize exercises benefits. This also points to a simple fact..
See why we get go excited!!
What isn't complicated is that exercise has the most profound effect on mitochondrial energy, function, and housekeeping.
At least 30 minutes daily. Cross between strength, aerobic, and even more intense work. Always work with your doctor and within your physical range.
Endurance training appears to have the greatest effect with 40-50% increase in mitochondrial makeup.
Let's turn to a new hack on the block.
A key player in the bacterial world, PQQ found it's seat at the mammalian table in…mitochondria (ancient bacteria after all).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
It has an important role in managing lactate, a byproduct of our energy production.
More importantly to our discussion, it's a huge boost to mitochondrial function:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
Goodness:
Technically, PQQ also acts an anti-oxidant. Does it adversely affect the results of exercise?
Good news on that front:
https://pubmed.ncbi.nlm.nih.gov/31860387/
The "stress" of exercise needs to be detected and PQQ doesn't appear to block this.
We use this one and cycle it with our mito stack (full list below). 20mg in the morning matches research and has a stronge safety profile.
PQQ is the heavy lifter in our toolkit for all things mitochondria and we'll do a deep dive shortly. It deserves the spotlight.
One note…high triglycerides or LDL cholesterol and/or low steroidal hormone function may indicate mito dysfunction and benefit from PQQ according to research.
Next up…urolithin a. What??
There's a new kid in town called urolithin a.
What does it do?
https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00118-0
Okay…so removal of worn-out mitochondria (mitophagy) and improved function.
Does this translate??
And how do we get it?
https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00118-0
They tend to have more varied gut bacteria so it's time to start eating balanced and varied diets with real food!
The signature:
https://www.nature.com/articles/s41430-021-00950-1
So…the Mediterrean diet (walnuts were a huge player there actually...not the olive oil).
The next best way is pomegranate extract such as this one.
There is a pure urolithin A supplement since some people do not have the proper gut microbiome but it's more expensive.
Next up…embrace the cold.
Check out our cold exposure and mental health or dopamine rescue reviews.
Once you understand the benefits of cold exposure, you're going to overcome your fear (hatred??) of the cold.
Most of the benefit resides around…mitochondria function!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545200/
PGC-1a - the kingpin of mitochondrial juicing.
What's the story?
It mainly revolves around brown fat (BAT - brown adipose tissue). Babies have lots of it and we lose it as we gain the ability to shiver.
Cold exposure brings BAT back online and the what exactly makes brown fat "brown"?
Mitochondria. Actually the iron in mitochondria as their numbers swell.
The body is panicking about the cold and juices up energy production to generate heat. That requires…more mitochondria and better functioning ones!
It also means getting rid of the laggers (mitophagy):
https://www.cell.com/iscience/pdf/S2589-0042(21)00402-8.pdf
More mitochondria. Removal of faulty ones. Better energy production.
Holy grail. Sorry…embrace the cold!
10 minutes at 50-60 degrees a few times a week will do the trick. Work with your doctor and listen to your body! Check out the reviews with more guidance and Huberman podcast has a great intro.
Next up…the balancing system.
We have a powerful system in our body designed to keep all other systems in balance (called homeostasis) in the face of stress.
Stress can be anything that pushes a pathway in one direction.
For example…the cold exposure above! After things start to warm up, the body needs to get back to center.
Hello endocannabinoid system!
Of the cannabinoids, CBD isolate is the best way to support this system since the others push or pull in one direction (which leads to tolerance). CBN, CBG, Delta8, and of course…THC.
As for mitochondria??
Goodness…let's get started.
First…the grab bag which speaks to how omnipresent the endocannabinoid system is:
https://pubmed.ncbi.nlm.nih.gov/34069407/
So, just…
The gang's all here.
CBD isolate has a huge impact on reducing the highly destructive waste material from energy production as well:
https://www.fundacion-canna.es/en/cannabinoids-inside-our-cells-their-role-mitochondria
Now watch this trick (this is where we geek out)...
CBD will actually INCREASE oxidative stress in cancerous of virally infected cells!
Remember…that's how our immune system naturally kills wayward cells. Chemo and radiation are just massive hits of oxidative stress.
But..CBD doesn't do this to the surrounding health cells! (see top 10 tools for fighting cancer).
In fact…it can protect neurons when under duress:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666323/
So...a response depending on the state of the system. Our favorite kind.
THC does not have the same profile unfortunately.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310259/
More on how CBD protects the brain from THC.
We use this one and dose range runs from 100mg to 300mg (peak neurogenesis) daily.
Next up…some protection please.
Whether the oil patch or deep inside our brains, energy production is a messy business.
The waste from our energy production is in the form of free-range oxygen. Little organic scissors running around our sensitive molecular wetware.
We don't want to squash oxidation as it's a powerful signal to tighten up the ship in mitochondria function…but, we could use some back up cleaning crews now and then.
COQ10 is a powerful player with a secret back door into our mitochondria!
We see the usual suspects:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025630/
There's SIRT (cellular shock protein) and PGC-1α, the mito ringleader.
CoQ10 is literally part of the energy production machinery as it carries electrons from one work area (complex 1, 2, and 3) to the next.
Just a head's up…statins rip COQ10 so many people are familiar with supplementing it for heart and brain health.
Just happen to be the two hungriest energy users. Go figure.
PQQ and CoQ10 may work together but the general thought is to take them at different times (PQQ in the morning due to energy).
We use this one here. Let's turn to fat…the good stuff cells are made from.
We have a monster review on the importance of Omega 3 fats and ALA is a big part of that discussion.
Alpha Lipoic Acid is a key ingredient of the mitochondrial energy complex:
https://pubmed.ncbi.nlm.nih.gov/31885820/
Biogenesis - making new mitochondria.
Keep in mind that mitochondria only exist for a few days so we're constantly cranking out news ones. Each cell can have a few thousand so this process is mind-blowing.
It's also going down as we age and in many (if not all) disease states.
Energy hungry equals mitochondrial vulnerable so…what about the brain (20% of body's energy usage) with aging?:
https://pubmed.ncbi.nlm.nih.gov/17605107/
or
Parkinson's is a very specific example of this and one of the key pathways tied to mitochondria turnover is literally called Parkin:
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-020-00367-7
ALA?
https://www.spandidos-publications.com/10.3892/mmr.2017.7974
Too bad we're consuming massive amounts of seed oil and omega 6 fats which compete with omega 3 for processing (read the reviews!!).
A little side-hustle of ALA appears to be its ability to offset the damage from iron overload in mitochondria:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387298/
In fact, this appears to be a running theme through our tools (see CBD and iron overload).
We use this one here and some brands combine PQQ and ALA.
Next up…the glucose problem.
The prefix ("carn") should indicate our sources for both of these.
Animal products (sorry vegans). There's no getting around a few million years of evolution and there's no way to get them from plantlife (despite our daily Pho habit).
First…carnitine:
https://ods.od.nih.gov/factsheets/Carnitine-HealthProfessional/
Okay…so ALA above is a long chained fatty acid of the Omega 3 variety. It needs transport in and carnitine is the bouncer at the door.
More importantly, it removes the waste material from energy production which gums up the works.
Carnatine levels decrease as we age:
https://pubmed.ncbi.nlm.nih.gov/11854488/
Carnosine is all about sugar. Or the damage from sugar.
We did a huge review on the problem with glucose and the slow build up of AGEs (Advanced Glycation End products).
Essentially, the ability of glucose to "stick" to just about everything in our machinery including fats, proteins, and even each other. The accumulation of which is directly tied to aging and dysfunction.
Carnosine (and GLO2 from glutathione) mop this up!
https://pubmed.ncbi.nlm.nih.gov/33350165/
What happens when these "blobs" of broken machinery build up in our mitochondria with aging?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058055/
Um...that's removal of brain amyloid beta plaques tied to dementia!
Mitochondria just work better when you remove the "gunk":
https://www.ahajournals.org/doi/10.1161/STROKEAHA.114.005183
Interestingly, carnosine just happens to be the initiator of….COQ10 creation!
https://www.researchgate.net/publication/351648766
Go figure! Big review of carnosine here. We use this one.
Let's turn to the great reset (done nightly).
Let's move past the the part where mitochondria are the main source of melatonin synthesis (along with steroid hormones which have huge impacts on sleep).
A study just came out that showed circadian rhythm dysfunction may be more dangerous than metabolic dysfunction!
https://pubmed.ncbi.nlm.nih.gov/36558476/
Fascinating! How you sleep is more important than how you...eat and excercise (essentially, metabolism bookends)!
Remember that 1/3rd of our whole program above is about removing faulty mitochondria. Mitophagy.
That's the PINK/PARKIN pathway which manage the breakdown of poorly functioning mitochondria.
Sleep is when the trash gets taken out!:
https://www.frontiersin.org/articles/10.3389/fcell.2022.956394/full
The beautiful lymphatic and glymphatic (brain) systems of waste removal.
That includes all the ROS and waste material from energy production that gums up our cellular machinery.
To summarize...
https://www.frontiersin.org/articles/10.3389/fcell.2022.956394/full
Fine…what about sleep deprivation and mitochondrial function?
https://pubmed.ncbi.nlm.nih.gov/29655867/
Goodness. Total energy-production bomb.
The entire energy complex breaks down:
https://www.sciencedirect.com/science/article/abs/pii/S0022395610000245
The hypothalamus is just the very vulnernable seat of memory and mood control.
Remember…this removal process is happening every day:
https://pubmed.ncbi.nlm.nih.gov/36092697/
A big part of sleep may indeed be cellular housekeeping around our energy complex…mitochondria!
We've looked at how progesterone, estrogen, and testosterone all have huge impacts on sleep quality.
They're also managed and manufactured…by our mitochondria which begs the question with aging…which drops first? (see steroids and longevity).
Here's our sleep toolkit and we have a whole section on CBD and sleep (since that's our original focus).
Expect more research on this front. One note…PQQ may directly support our circadian rhythm by re-aligning cortisol (the primary wake signal) rhythm:
20mg at 8 weeks. Go figure….support of mitochondria causes a virtuous loop that then translates into…
Let's turn to the known player with fascinating results.
Research is pretty well established on calorie restriction, fasting, intermittent fasting, and even Keto (a selective form of starvation) and longevity or any metric of health for that matter.
We know AMPK gets ramped up.
By reducing energy creation, calorie restriction allows for a more efficient mito complex:
https://www.pnas.org/doi/10.1073/pnas.0510452103
To translate, CR (calorie restriction) or fasting or keto, etc:
Basically, it's like running your engine below the redline. You could argue it's akin to what happens during sleep!
In fact, removal of bad mito also occurs:
https://pubmed.ncbi.nlm.nih.gov/32856431/
AMPK and mTOR are big guns managing the show but it's a mitochondrial production through and through.
SIRT is just the foot soldier with access to DNA keys.
Even intermittent fasting (like the 16/8 schedule…no eating for 16 hours..say from 6pm to 10am) can claim this effect.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942780/
TCF is "time controlled fasting". Like 16/8.
Even our energy plants need "downtime" for maintenance. Appears to be a universal law.
That's a wrap. We'll do a deep dive on PQQ since it's so impressive in research.
There are a few stragglers at least deserve a mention.
We'll go through these fast.
Magnesium glycinate is a key building block for the mitochondrial complex:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516748/
And supplementation…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485371/
DD and DM are measures of heart dysfunction…a big consumer of energy.
We have a huge review on magnesium glycinate (cross the blood brain barrier…the other big user of energy).
Glutathione is our key detox pathway. The "ox" in detox is from oxygen as in ROS (Reactive oxygen species) that leak out mitochondria.
It's a big deal to keep the local mito environment from burning itself down:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821140/
Big review on glutathione or oxidative stress.
One easy way to support is NAC.
This becomes apparent in disease states that reflect mitochondrial dysfunction:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698433/
Big review on NAC here. Buy here
We're getting into the currency of energy production now.
There's competing and conflicting views on which is better but they all support NAD, the carrier of energy around the cell.
SIRT requires NAD to function and there's clear interaction with mito function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565489/
NAD can be directly supplemented as well and we'll leave the horse race to others on which is better to support this whole pathway (with NAD being the ultimate goal).
Finally…B vitamins.
They're all over the place here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379835/
Check for MTRR or MTHFR gene variants and consider a methylated B complex.
It's a simple building block but an essential one!
Of course, Vitamin D and steroidal hormones (bioidentical) are critical to everything we've discussed. Work with your doctor and get your levels tested!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
So…are there tools and pathways we can look at to reduce risk and affect clotting especially around the amyloid type that DON'T build tolerance?
Of course, work with your doctor or naturopath…this is not medical advice. Some of these players essentially thin blood so other meds (like blood thinners) must be taken into account.
We'll focus on three interconnected lines with amyloid clot pathways being primary:
A great deal of the research will come from amyloid formations in dementia, prions, etc since that's where the research is more fleshed out.
Let's get started with these topics:
Let's get started! First, know thy enemy!
The goal is to protect from dysfunctional clotting and help the body remove foreign entities. An endeavor not that different from dementia (see big review on dementia).
We're going to focus on amyloid fibril clotting. Amyloid beta is the primary accumulating substance with dementia.
Essentially, amyloid is a result of our immune system's arsenal against bacteria. It will stab bacteria with a long lance called a fibril.
https://www.science.org/doi/abs/10.1126/scitranslmed.aaf1059
The problem is that it can clump together and form long tendrils…like a balled-up fishing wire.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634529/
Another big player is fibrinogen which starts the blot clot cascade of responses.
In fact, the interaction of fibrinogen and amyloid may be critical:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540762/
Abnormal clot formation indeed.
So…are there tools that can help us address amyloid accumulation and the associated clotting?
Let's get to it! We'll start with clearance mechanisms first. Our money is on nattokinase, glutathione, myricetin, and CBD isolate but the research will tell the tale below.
Our primary detox system in the body is called glutathione. It's known as our default anti-oxidant (C and E figure into its recycling), but it's also the primary way to address toxins, chemicals (alcohol eats it up in the liver), and even….amyloid formation!
We'll piggyback Alzheimer's research:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471116/
More importantly to our discussion…boosting its level can directly affect this clotting pathway:
https://www.sciencedirect.com/science/article/abs/pii/S0197018620303223?via%3Dihub
Turns out that glutathione function directly manages fibrinogen activity:
https://pubmed.ncbi.nlm.nih.gov/18570468/
So…more glutathione, less clot-forming initiation by fibrinogen.
Go figure.
You can take glutathione directly and we use this one (after bouts of infection, etc.).
More on oxidative stress or glutathione.
Another way to support glutathione is NAC.
NAC has gained recent fame for countering the effects of infection and more. We've loved NAC for quite some time due to its effect on oxidative stress and mental health.
NAC directly supports glutathione as it supplies a rate-limiting player (cysteine) in its creation.
NAC also acts as a sink for excess glutamate which just gushes out when the immune system is hyperactive and can be toxic to neurons and tissue.
As for the amyloid building process:
https://www.nature.com/articles/s41467-021-22120-4
That's a heart issue where amyloid accumulates due to a genetic issue and eventually causes heart attacks.
Interestingly, NAC supports glutathione which "breaks oligomers into monomers."
Literally, deconstructing the buildup at the chemical chain level.
And as for fibrinogen and the clotting cascade when excessive:
https://pubmed.ncbi.nlm.nih.gov/3716022/
Read more on NAC. We use this one.
Next up…an exciting option from Japan.
A very popular tool used in Japan from fermented beans is about to become really common in the US and Europe.
Nattokinase is a well known player in anti-thrombosis (reducing blot clots):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372539/
And the amyloid question??
https://journals.sagepub.com/doi/full/10.1177/1177271918785130
Goodness…Strike 2 for clots!
We're really leveraging the powerful effects of the bacteria strain used to ferment the beans but we all know that the gut and its microbiome are key to almost every pathway these days.
We use this one here.
Comparing the side effect profile and effectiveness, it's hard to understand why this isn't first line treatment. Work with your doctor or naturopath…nattokinase is a powerful anti-clotting player on par with standard medications.
Another powerful player.
Big write-up on myricetin but we discovered this gem from a different pathway involving dopamine and obesity (plus just about every addiction out there).
Myricetin is a bit of a workhorse though as a GLP1 agonist (more on that in the review).
https://www.sciencedirect.com/science/article/abs/pii/S0927776519307842
Bam!
It suppressed the formation to begin with but more importantly...
More research is starting to bare this out:
https://mural.maynoothuniversity.ie/6864/1/GJ-Myricetin.pdf
HEWL is a hen-based platform to study clots.
Myricetin appears to block the formation of new amyloid as well:
https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cbic.202200216
So...it prevents the transition to a stable structure for the clot.
And the primary clotting aspect (fibrinogen):
Thrombus…clotting!
Again…check out the review. Myricetin also displays neuroprotective effects.
Next up…close to our heart.
Big reviews on CBD and dementia or CBD and neuroinflammation but let's zoom into the amyloid formation piece.
CBD directly affects this pathway by stimulating the endocannabinoid system and a particular pathway called PPAR:
https://pubmed.ncbi.nlm.nih.gov/24288245/
Let's translate the Klingon, please.
APP is short for amyloid precursor protein…it's needed to get the amyloid party started.
CBD reduced this key ingredient which causes a decrease in amyloid (beta in this case) formation.
Here's the critical piece in terms of our bodies!
So…CBD helped neurons which are genetically programmed to build lots of amyloid and then die (like brain tissue with dementia)...survive!
After all…that's the real outcome that matters since amyloid removal itself is not coming through in dementia research and medication.
It needs to reflect in actual behavior, right??
Okay then…
https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/full
"Deficits reversed by CBD" in mice that are genetically programmed to make amyloid in spades.
This is in the brain…across the blood-brain barrier. Hard to get to. Harder to affect.
We use this one here. Hold under the tongue up to 60 seconds and 300mg daily is peak neurogenesis (brain repair process) as a benchmark.
The immune balancing aspect is just a bonus since amyloid is driven by that system.
Next up…an old standby.
You're probably tired of the fish oil list of benefits but it really is pretty impressive.
We did a giant review of omega 3 versus omega 6. The inflammatory effects between the two are night and day and we're swimming in omega 6s (seed oils, processed foods, etc).
So…what about those amyloid clots?
https://pubmed.ncbi.nlm.nih.gov/27789520/
Oh goodness…our favorite "system". We'll cover the glymphatic system below in the sleep section but put a bookmark by that one.
So…Omega 3's support the process that removes the waste from our body and brains…including amyloid particles.
Look what happens when you combine omega-3 fat and Vitamin D:
https://newsroom.ucla.edu/releases/vitamin-d-omega-3-may-help-clear-242465
We have a massive review on Vitamin D which directly manages our immune response along with steroidal hormones: testosterone, estradiol, and progesterone.
It's so much more than reproduction! The immune system is front and center.
Remember…part of the equation is righting the immune ship so that we don't keep making more amyloid material. This is all immune!
As for the clotting aspect:
https://pubmed.ncbi.nlm.nih.gov/15217806/
Here's the exciting part there:
Some people have clotting issues in response to a cue or pathogen….others don't.
This may speak to that difference! Too bad we're swimming in omega 6 acids which are compete with omega 3 for processing.
Let's turn to a behavior we can do.
The research is just crazy on this front. We're going to do a deep dive next for mental health and cold exposure.
Even 10 minutes in a cold bath (around 60 degrees) affords most of the benefits.
Daily before noon ideally. Run it by your doctor and take magnesium glycinate (or mag salts in the bath) and B vitamin complex.
Cold exposure has a powerful effect on rebalancing and strengthening our immune system.
So…first, the poor mice:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437631/
Mice who are genetically designed to get the animal version of Alzheimer's show reduced induction of tau and amyloid formation as well as the resulting behavior deficits after cold exposure.
There's a known connection between immune dysregulation, amyloid formation, and metabolic health.
Obesity drives these formations…especially in the bloodstream:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410081/
Vascular dysfunction. The stuff that leads to heart attacks and strokes.
Cold exposure fine-tunes metabolism and as a result…a direct effect on the formation of these micro-clots.
It goes deeper than that (we're complicated after all).
There's a cold-shock protein called RMB3 which may be conserved from distant relatives (such as bears) who lose a lot of brain matter during hibernation only to regrow it when they wake up!
Big review here:
https://www.bbc.com/news/health-54531075
The net net for our discussion??
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338605/
So...this cold shock protein was key to the repair/rebuild of the brain.
Okay…prion infection. Another flavor of amyloid tangles that can actually grow:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601216/
Watch for research on fgf21 pathway which cold exposure boosts...
https://www.nature.com/articles/s41598-021-00906-2
"Vascular stenosis" - narrowing of veins/arteries due to damage.
Look…read our dopamine rescue guide.
Any discomfort or pain you experience with cold exposure will directly translate to even more satisfaction/pleasure afterward. It's just how we're built.
You're buying future pleasure on account!
Let's turn to getting the immune system in check.
Huge review on medicinal mushrooms and mental health with a focus on the immune system's effect.
Medicinal mushrooms have powerful effects of rebalancing our immune system and it's clearly driving the amyloid clotting activity.
https://www.sciencedirect.com/science/article/pii/S0753332221001621
This immune "setting" (TH1 versus TH2) is critical to why some people's immune systems over respond versus other people's immune systems which don't.
It also goes to the formations themselves…
IOE is an extract of the Chaga mushroom.
And the clotting factor fibrinogen?
https://pubmed.ncbi.nlm.nih.gov/17205040/
"Fibrin degradation pathway". Breakdown and remove. That's just one species!
We have a massive review of medicinal mushrooms. We take this one here to get different species.
Let's turn to an unsuspecting player.
We all think of melatonin for sleep and yes, it's a key manager of sleepiness.
Made from serotonin (which is boosted by estrogen and conversely, testosterone in the male brain), melatonin is getting recognition for a wide range of neuroprotective benefits.
It makes sense since most repair is done when we're sleeping (more on that below…so important).
Mother nature likes to multitask.
Okay..so both formation and protection from effects:
https://www.nature.com/articles/aps20063
Goodness. Just sleep indeed.
But does this translate into effects we can feel??
https://alzres.biomedcentral.com/articles/10.1186/s13195-016-0206-x
As for fibrinogen and clotting??:
https://pubmed.ncbi.nlm.nih.gov/18289163/
Next up…your steroids matter.
We have massive reviews on testosterone, estrogen, and progesterone.
Every cell in the body has receptors and they directly govern our immune system.
These are just a few examples.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473201/
Goodness…they manage the removal of waste including amyloid formation.
That's not great news since progesterone drops by 50% by age 40 and estradiol drops through the floor late 40s (we learned the hard way - that story is here).
T's no slouch:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15568/
Look what happens when testosterone is just cut off:
https://academic.oup.com/endo/article/159/12/3885/5094961
And why aren't you supplementing with bio-identical since it's dropping 1% a year starting around age 20??
Estradiol is even more severe but progesterone is a monster calming agent for immune response and inflammation.
Autoimmune hits women 8:1 and the '40s (when P is really dropping) spikes this effect.
In fact, autoimmune will go into remission during pregnancy when P is highest.
Get your levels tested and watch out for the "your levels are fine for your age."
And situations where clotting is hyperactive?
https://www.jhltonline.org/article/S1053-2498(16)00244-8/fulltext
Bioidentical:
Read the reviews…there's no band-aiding loss of steroids.
Finally…we have to talk about sleep.
Whether the lymphatic system (body) or glymphatic system (brain - newly discovered), this is the key to the removal of waste material and malformed entities.
It primarily happens in the last half of sleep (4 am on) and during stages 3-4 of deep sleep (generally 1 ½ hour cycles).
Just look at bad sleep:
https://www.pnas.org/doi/10.1073/pnas.1721694115
Goodness.
The waste removal systems work when we sleep (deeply) and this is why it's important:
So…how's your sleep? Thought so.
We have to address sleep for our bodies to naturally remove the substances that eventually congregate to form clots.
We have a whole review on sleep but here's our sleep toolkit. We need a deeper dive on this front since it's so critical to the clotting issue.
Of course…one more feather in Vitamin D's cap:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031886/
Aim for 60ng/ml based on the endocrinologist's data (see big review). Get levels tested.
A few final notes that need to be addressed.
We focused on tools that don't build tolerance or have potential longer-term issues.
There's conflicting research on aspirin (even baby aspirin) a known anti-coagulant.
Specifically, as it applies to amyloid driven disease for stroke and heart:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931649/
Essentially, substances that affect COX pathways (NSAIDs, etc.) may cause micro-bleeds in these individuals.
We just need more info.
As for turmeric (which is very interesting across many pathways), there's some conflicting research around increased bleeding we would like ironned out first.
And cinnamon…discount aspirin!
Interesting results there but there's a liver toxin naturally found in cinnamon called coumarin.
Longer term, we would like to see more research. Remember that glutathione is the primary detox agent in the liver so we don't want to draw that down.
Of course, work with your doctor or naturopath especially if you take other medications.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>Can we support dopamine without the spike drop yoyo of tolerance
]]>Once you get to really know dopamine, seeking balance and support becomes almost a…passion.
That's actually the correct word to express the root effect of dopamine.
Passion. The definition:
We'll touch base on what dopamine really is (not the "pleasure" you've been promised) below but more importantly…
Dopamine is under assault these days. Actually…it's exhausted.
We'll look at the primary insults, how much they spike dopamine, and what this means for your general feeling of…zest! Loving life and what you're doing.
After all, that's what's at stake here.
More importantly, we'll cover new research on tools that naturally support dopamine…some of them are behaviors and others as supplements you can take.
One caveat…no tolerance. No addiction. Naturally, support our baseline dopamine.
Here are the topics we'll cover:
We'll wrap with the grab-bag list and a quick but very important send off note regarding early trauma, infection, and stress - must read if you really want to rescue dopamine (and every other messenger in the brain!!).
Let's get started!
We've all heard of dopamine as the "reward circuit" (true) and also tied to pleasure (less true).
Let's clarify a bit.
At its top level function, dopamine is an anciently conserved (worms have it) driver of behavior or action that increases survival odds.
So…wrapped up in this "mission statement" are a host of different effects:
What is the net effect of this?? Not really pleasure but more….satisfaction.
Just like serotonin isn't the "feel good" transmitter so much as "feel right in your own skin" player.
They're intimately linked by the way as we'll see below.
That just scratches the surface though!
Dopamine is a very dynamic system with two different components:
Tonic is our baseline level and it can differ across people depending on genetics, past trauma, diet, sleep, etc.
The level of tonic dopamine speaks to your general level of motivation or desire to "seek".
The difference between the two speaks to how "beneficial" that last behavior (could be sex…could be cocaine) was perceived as.
Now…we can quickly get lost in the weeds but here's the key…
Dopamine exhausts when it spikes.
There's always a "hangover" effect when something is really rewarding. The more the reward, the more the following drop.
In fact, the spike goes away and the "pool" of dopamine (tonic) also drops temporarily.
Goodness…pleasure now is bought on credit!
You'll have to pay it back with interest (pain or discomfort).
So we have to be careful. We want tools that do not just jack up dopamine in one direction.
Or you pay for it later!
With that in mind, let's get started. Our dopamine system is overrun these days!
Goodness…no wonder we're not feeling very…passionate.
Let's get started with a general tip that's so powerful.
It's simple.
If we're constantly spiking dopamine (the phasic or spike piece), we'll slowly deplete our natural pool of dopamine for the future.
Doom-scroll your phone for about an hour and see how you feel after. Or how about the morning after a fun night of drinking (alcohol boosts dopamine levels)?
Interestingly…what does the removal of dopamine feel like?
Emotional and cognitive PAIN!
Or malaise…a general inability to move, function, and feel motivated.
Dr. Huberman gives a master class on dopamine here. He descibed a temporary block of dopamine from a medication as the feeling of...abject misery!
So..how can we use this to our advantage?
Essentially, like with any kind of tolerance (and this may be THE primary form of tolerance), we need time away.
Let that pool fill back up! Dopamine is also a reward prediction machine. A type of learning in the brain.
There's an intermittent aspect to it. That's why gambling is so compelling. Sometimes you win. Sometimes you lose. Totally random.
Dopamine LOVES this! It's like a puzzle it's trying to figure out for survival (money = food, sex, water, etc in our world).
So…if you always smoke out (dopamine) before eating (dopamine) and you're trying to dis-entangle this…flip a coin.
Heads you do, tails you don't. Check out our review for Tapering THC and Cannabis for more tools as an example.
Block out cell phone checks for periods of time.
The future is going to belong to those that can self-moderate the endless sources of dopamine firehoses we encounter now.
I feel blessed to have been born in the 70s before all this enticement!
In the meantime, take the things you're most craving and take breaks. Find balance.
If this sounds impossible, the tools below will help the transition.
Let's get started!
Stay with us...I know...it sounds crazy and impossible to get in cold water but just read the next bit.
Very interesting research on cold exposure and dopamine.
We're switching the direction:
You're buying future satisfaction with current pain (reversing the pleasure seeking pain avoiding path).
Researchers have known this for quite some time:
https://pubmed.ncbi.nlm.nih.gov/8926010/
Here's the fascinating piece…
Cocaine spikes dopamine but it drops very fast and very sharply followed by a reduction in tonic (ocean level) dopamine.
Cold exposure is boosting the general "function" of our dopamine system!
What on earth is going on here?
Two things pop out.
First, cold exposure appears to reduce dopamine activity…essentially giving it a break. Think of tolerance in reverse!
https://www.nature.com/articles/1395596.pdf?origin=ppub
We see this effect all over the body (glutamate receptors and pain; insulin receptors and sugar, etc).
Too much for too long causes burn-out at neurons. Give them a break and they come back online better than ever!
The other is more of a neurotransmitter hack!
Adrenaline (norepinephrine) is made from…dopamine! It's how dopamine get's us up and running.
Not only fight or flight but just being able to get out of bed (lower levels of adrenaline gets us moving AND focused).
Cold exposure tricks the body into thinking it's in immediate peril! It needs adrenaline to respond and that kickstarts the middle person…dopamine.
Really exciting tool to rescue dopamine longer term. Also, good luck feeling depressed or anxious after cold exposure!
So…check out Wim Hoff's book or content on cold exposure. Great first guide.
Go slow. Breath. Understand that you're buying future pleasure/satisfaction with the initial pain. You're paying off your passion credit balance!
Even 5-10 minutes at 60 degrees (a cold bath) can trigger many of the benefits.
Work with your health status and and doctor/naturopath. Again, Huberman's review is impressive and actionable.
Let's turn to a different kind of tool.
Our original interest in CBD isolate and dopamine specifically came from studies on schizophrenia and psychosis of all things.
This brutal disease is characterized by too much dopamine in one area (striatum - the so-called "positive" symptoms) and too little in another area (pre-frontal cortex - the so-call "negative" symptoms).
Imbalance in different brain areas.
The anti-psychotics basically pound dopamine to at least lessen the paranoia, hallucinations, etc from the striatum hyperactive dopamine function.
CBD showed impressive results for this area while not depressing the pre-frontal cortex!
https://pubmed.ncbi.nlm.nih.gov/28185872/
Hmmm…mesolimbic substrates. Dopamine's territory!
In fact, there was an improvement in cognitive function (pre-frontal cortex). See the full review of CBD and psychosis or CBD and dopamine but this reflects similar effects we see everywhere.
Different responses depend on the state of the system (or even separate brain areas!!)
The cannabinoid system manages deviation from balance in the dopamine system!
THC pushes activity too hard and too long at the CB1 receptor so it can actually cause tolerance (long term dopamine dysfunction) and to a lesser extent, addiction (about 9% of users).
CBD shows no signs of addiction, tolerance, or withdrawals.
More importantly for our discussion, half of the dopamine rescue is calming the craving aspects of harmful behaviors we have now.
Let's look at the worst of the worst…opioid addiction and craving:
https://www.tandfonline.com/doi/full/10.31887/DCNS.2020.22.3/
Check out the review on CBD and addiction or CBD and craving.
This is dopamine misdirected people! And CBD appears to bring this system back in line.
Again…big review on CBD and dopamine here. 300mg daily is the level for peak neurogenesis...literally brain rewiring (dopamine's a learning driver after all). We use this one here.
This effect may actually be due to its powerful big brother in the brain. Serotonin.
You can't rescue dopamine without addressing serotonin first. There's an intricate dance between the two!
Serotonin is the master regulator of ALL human behavior:
And on and on.
It gets incredibly complex teasing out the interaction between serotonin and dopamine but the simple sketch is this:
Generally, dopamine wants more more more.
Serotonin provides a negative assessment of these "impulses".
So…
https://journals.sagepub.com/doi/full/10.1177/2470547021996006
Goodness…the prefrontal cortex (seat of serotonin) is offline during puberty remodeling. Impulse control issues much!?!?
Also, dementia shows intense atrophy in that brain area as well. Same issues.
So…we need healthy serotonin to keep dopamine in check or we'll be spiking it into oblivion.
Check out our review on serotonin or serotonin and self-esteem (fascinating) or more importantly…our serotonin rescue page coming soon.
One big clue…with longer-term SSRI use (pump up serotonin till tolerance sends it the other way), we see drops in dopamine (and libido, joy, etc):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674976/
Check out the problems with SSRIs or PSSD (post SSRI sexual disorder).
Libido is square in the wheelhouse of dopamine (sex, the act and craving of it directly boosts dopamine…or should anyway!).
Our SSRI rescue kit looks at how to naturally support serotonin.
Next up…a curious addition.
Most "drugs" adversely affect dopamine longer term. They spike it and our baseline levels drop accordingly.
Caffeine is a bit different. It may actually increase the density of dopamine neurons in the brain!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462609/
This is important. If there was dopamine tolerance (a longer term reduction in function), we would see fewer receptors over time.
Yerba Mate adds a whole other element!
https://www.mdsabstracts.org/abstract/yerba-mate-ilex-paraguaiensis-protects-dopaminergic-neurons-degeneration-and-improve-their-maturation-in-culture/
Okay…this is the direct opposite of dopamine dysfunction. The neurons tied to dopamine function are literally growing connections.
If you can, look for low sugar options and early in the morning since caffeine opposes adenosine which manages your sleep/wake cycle.
Anything that protects dopamine neurons and function is a go!
Now, a new and fascinating addition.
We have a big review on myricetin.
It's a GLP1 agonist like the new blockbuster obesity drug, Ozempic but without the nasty side-effect profile.
GLP1 is a gut signaller to the brain that nutrients are satisfactory…turn off appetite.
Here's the fascinating piece…the brain likes to multi-task and the root driver of GLP1 activity is partially driven by…dopamine!
As a result, researchers are seeing a reduction in cravings across multiple drugs from GLP1 activity:
https://www.frontiersin.org/articles/10.3389/fnbeh.2020.614884/full
Of course…dopamine is always in play with addiction so..
https://pubmed.ncbi.nlm.nih.gov/29337226/
Part of rescuing our dopamine system is "editing" out old habits and addictions. Otherwise, they're spiking our phasic dopamine and slowly eroding our baseline.
Myricetin is an option available now to mirror pathway effects of the $30K/year drug being prescribed in boatloads (with a pretty significant side-effect profile).
Let's turn to the bizarro world of dopamine in terms of feel-good behaviors.
Here's the simple equation that will change your life.
For a period of time.
Let's look at some common triggers to see how much they spike dopamine above baseline:
Goodness…meth is absolutely destroying dopamine function and guaranteeing that it's THE focus of the brain.
The drop afterwards is going to be brutal!
That's the key point…think of dopamine as a credit card. When you spend now (that chocolate croissant), you'll have to pay back later (feel down).
The "account" always wants to get back to zero but it will swing.
The absence of dopamine is just absolute emptiness and misery. Huberman recounts a time when his dopamine was blocked medically (podcast above).
A few key notes…
The more random the better. Not only does this increase your baseline but it will make the things you like…MORE enjoyable.
This sounds great but if it were that easy…
Let's go there now. Time to Jedi mind-trick your dopamine system.
Remember…dopamine runs the roost for our older brain areas (the "reptilian" brain) which hasn't changed much since…well reptiles!
Impulse. More. Now. Novelty. Damn the repercussions!
It's easy to think…we'll I can't fight those urges…they operate outside my conscious control.
Here's the interesting piece.
We've added new hardware onto that old-world brain which got us through a few million years.
The prefrontal-cortex. The part behind your forehead that makes humans…human!
I absolutely hate cold water. I blame it on my southern French heritage (mom's side) but genetically, I just don't have the cold exposure hardware. Hate it. With a passion.
That being said…I "know" just how powerful dopamine is to…well…everything!
Everything I want to do in this life. This completely colors how I view cold exposure now.
Every time I get in that cold water, I'm buying future happiness and satisfaction. It's the reverse credit card.
Literally, the stuff that makes life worth living is imbued in that cold water. I crave it now! I look forward to it. Seriously. Because…I KNOW.
That's the power of the prefrontal cortex. We can rationalize almost anything. We can create cravings for work, hardship, pain, and discomfort.
If we know that this will directly increase our sense of well-being, wonder, and drive.
Remember…the pain and pleasure centers are the same in the brain (check out Dr. Lembke's work on this - Dopamine Nation is the book).
https://news.umich.edu/pleasure-and-pain-study-shows-brains-q-pleasure-chemicalq-is-involved-in-response-to-pain-too/
Embrace hardship. Discomfort. And watch how good you feel in the other 23 hours of the day.
The cold exposure above is a perfect example!
Let's turn to another immediate tool for proper dopamine function.
We have massive reviews on the following:
First, T and estrogen both drive serotonin and we saw above how it helps manage dopamine function (especially to the top end).
In general, T and estrogen are pro-growth, repair, and replenishment.
Just look what happens when gonads are removed:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025724/
Goodness. Axon density…literally a reduction of neurons that carry dopamine's signal.
A loss of permanent dopamine function.
Just for reproduction, right??
And progesterone, the opposing force to estrogen?
https://au.atpscience.com/blogs/blog/how-does-progesterone-create-a-dopaminergic-response
It drops by 50% at age 40 for most women. Just saying…
We learned the hard way with a brutal perimenopause.
Then there's Vitamin D, a steroid we used to get from the sun for which many people are deficient.
I don't know where to start…over 1000 chemical transactions use D including many with dopamine function.
First...
https://www.sciencedirect.com/science/article/pii/S2251729413000050
This speaks to the protection of the dopamine system…especially from drugs and toxins that spike or destroy it.
https://www.semanticscholar.org/paper/Vitamin-D-regulation-of-GDNF%2FRet-signaling-in-P%C3%A9rtile-Cui/1d986c7145f03012681243007726c560f5cf0936
Check out our review of Vitamin D for mental health.
Get your steroidal hormones and Vitamin D tested. Supplement as needed!
Another safe and effective tool for dopamine rescue.
Mag is a powerful player across the body and brain with dopamine also affected.
That's not good news in light of this:
https://www.ncbi.nlm.nih.gov/books/NBK507254/
Here's the fascinating piece.
Dopamine is a member of the family that drives action…matriarch actually of catecholamines! Adrenaline. Glutamate. All intimately tied.
Mag supports the calming opposing force (mainly GABA).
When mag goes down (stress is a huge factor), dopamine runs wild!:
https://www.ncbi.nlm.nih.gov/books/NBK507254/
Too much dopamine is tied to mental health issues, insomnia, ADHD, etc. Anytime the brain is running too hot. We looked at whether daily cannabis use is tied to too much glutamate as an example.
Mag is a great mineral dampening field on excessive activity there and remember..part of rescuing dopamine is avoiding excess (or there's payback the other way).
Dopamine's funny in that…the more you use it, the less you get in the future. Balancing the extremes is critical.
Check out the big review on magnesium for mental health.
You only have about 400,000 neurons in the brain that generate dopamine.
Okay…this a drop in the bucket! Out of 86 billion total. 0.00000465116 Goodness.
Dopamine can't cross the blood-brain barrier although the vagus nerve may signal production from the gut where dopamine is made by gut bacteria (more on that below).
So…how do we protect and support these neurons?
Next…we have to support BDNF, the fertilizer of the brain!
I can't express how important this is in light of all the insults the brain endures:
We need to protect that small band of 400,000 neurons!
For example…
https://pubmed.ncbi.nlm.nih.gov/25693197
Parkinson's is a loss of these neurons (see Parkinson's review).
And the striatum…
https://www.frontiersin.org/articles/10.3389/fncel.2014.00254/full
BDNF is literally the construction (and remodeling) crew for your dopamine system.
So…how do we support BDNF??
Great tools:
Big review on all of those since BDNF is THE key to addiction (hello dopamine) and mental health.
Finally…the runner's up.
Tools that may support dopamine function, don't build tolerance, and are generally considered safe!
Most of these revolve around the repair side (BDNF, serotonin, etc) or the insult side (inflammation, glutamate excess, etc).
Quick takes…
This is the gut connection (our gut bacteria - more on probiotics).
A look at Parkinson's:
https://www.nature.com/articles/s41392-020-00456-5
It did this by boosting TH, the rate limiting conversion of l-dopa into dopamine.
That's a great way to support…we're not directly boosting like with l-dopa or tyrosine.
In fact, low dopamine may be a result of gut imbalance for some people.
Big review on berberine.
Curcumin (turmeric) has many effects but one of them is to slow down the pathway (MAO) that brakes down key neurotransmitters.
The result:
https://www.frontiersin.org/articles/10.3389/fpsyt.2020.572533/full
In fact…some people have a "fast" version of MAO and therefore, just rip through their neurotransmitters. Another key cause...
It also supports BDNF!
Check out the big fats guide. Sooo important these days.
Seed oils and processed food may be dopamine's worst enemy and it comes down to omega 6 fats outgunning (they compete) omega 3s.
For example:
https://academic.oup.com/ijnp/article/17/3/383/758961
Goodness…there's MAO (the dopamine removal system) and increased binding. That means function…key since we don't want to just juice up dopamine!
The big fats guide.
Ginko's biggest impact may be in decreasing oxidative stress in the brain while increasing blood flow.
The net effect:
https://www.healthline.com/nutrition/dopamine-supplements#TOC_TITLE_HDR_15
The "long term" is key for us. We don't want tolerance!
Finally…the monster player with brain healing.
A big part of psilocybin's mechanism relies on serotonin and we know it's integrally tied to dopamine…so???
https://www.jstage.jst.go.jp/article/bpb/38/1/38_b14-00315/_html/-char/en
We like indirect! Also, the research on psilocybin and other addictions is just breathtaking.
Check out the big psilocybin review but addiction is about to have a major adversary.
This brings us to the final takeaway. Maybe the most important part.
Newer research is showing that psilocybin's long term effect is due to genes being turned on/off in... the immune system!
It makes sense..how could one psilocybin use cause such profound effects..for months or years!!!
Dopamine (or serotonin) quickly return to baseline (and go even lower) after a spike.
We're talking about long term structural changes.
This is the future of mental health and feeling great.
We have a big review on editing your mental health past but a quick take.
Early trauma, infection, or stress can dysregulate all these systems longer term (including dopamine) and the "markup" is made in our immune system.
A catalog of past insults. Even in utero or from prior generations.
Psil's secret weapon is an ability to "edit" these markups!
And dopamine specifically??
Wait for it….
https://www.frontiersin.org/articles/10.3389/fpsyt.2021.744690/full
Goodness. ELS (Early Life Stress) changes (for the worse) both tonic and phasic dopamine levels.
This has a big impact on "risk" of addiction by the way. It's self-medicating because loss of dopamine feels like...crushing dispair.
The interaction with early trauma, stress, or infection has many effects from dopamine alterations:
People…you have to remove this burden from your dopamine system FIRST.
Dopamine function may just be reflecting past insults.
Check out related research:
Okay...that's a wrap. Go get your dopamine back. Myricetin, Vitamin D, mag, and CBD isolate are great tools to make the harder work...easier.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
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Is myricetin a natural hack for the powerful GLP1 pathway?
]]>The medical field is all abuzz with so-called GLP1 agonists for obesity these days.
Don't worry..we'll explain what they are below but the more fascinating piece surrounds upstream mechanisms around craving, addiction, and…dopamine!
Semaglutide (Ozempic) is the possible blockbuster drug at around $30K annually that's driving this attention.
There is a different way to boost this same pathway with supplements such as myricetin, a common phytochemical found in red wine and other fruits or vegetables.
In fact, you can supplement myricetin directly.
My personal story with myricetin?
I'm seeing habits that have been thoroughly entrenched for decades just melt away.
For example, I've always stayed up later than I should… 12 am to 12:30 even though I know the scientific research shows a clear benefit to 11-7 circadian rhythm adherence.
I just felt like I was losing "my time" even though it was the same old scrolling, video games, etc.
Again…30 years of this pattern. Felt like it was "part of me".
2 weeks into myricetin, I'm in bed at 11 pm. That's just one example…of many.
Food choices. Appetites (plural) for all sorts of things that are not good for my health.
Yes, this is anecdotal but it's also unprecedented…in my life anyway!
What's going on here? Is it just me?
Turns out…No. There's actually literature on GLP1 agonists and this effect. So weight loss and appetite changes may just be a result of a powerful regulation of the reward system where dopamine is king and queen!
Let's take a look at this with these topics:
Let's get started!
GLP1 is one of the many new novel pathways that we're finally starting to understand.
It's a big gut player…a signaling agent to the brain of the presence of sugar essentially.
It triggers insulin release and slows the production of glucose (via glycolysis) in the liver.
Essentially…it's a gut-based (front lines) signal that food supplies are adequate!
The net result that everyone's so excited about when boosted:
Satiety. Feeling full.
The research numbers on weight loss are pretty ridiculous for such an intractable problem as obesity.
https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/expert-answers/byetta/faq-20057955
Okay…you have our attention.
So…this class of drugs boosts (agonist) GLP1 activity in the body.
Here's where things get interesting.
A "side effect" of GLP1 medications for diabetes and/or obesity was…a significant reduction in alcohol use among people that are abusing the drug.
When you block GLP1 activity, you see the opposite effect:
https://pubmed.ncbi.nlm.nih.gov/29337226/
That was just the first inkling (easy to spot since alcohol use is so common).
Then came nicotine, amphetamines, and more:
https://www.frontiersin.org/articles/10.3389/fnbeh.2020.614884/full
Wait…what??
We just listed some of the most problematic drugs in terms of craving and addiction.
Amphetamine is probably front and center!
No wonder:
This speaks to obesity almost being a form of food addiction. Okay…so let's go there now. Read our fats review...you'll see why that might be true.
If it's addiction…dopamine's in play.
We have a massive review on rescuing dopamine since it's so key to passion, motivation, and…addiction!
We have a review of dopamine but let's cover the broad strokes as it pertains to addiction and habits.
Part of our reward system, dopamine has multiple powerful facets:
All habitual and addictive behavior requires dopamine to spike in a particular area of the brain called the nucleus accumbens.
So…what on earth is a nutrient sensor in the gut doing meddling in this area?
Hello GLP1!!:
https://pubmed.ncbi.nlm.nih.gov/28315693/
So essentially, GLP1 activity prevents cocaine from adjusting our baseline dopamine levels in these very important "habit reinforcing" areas of the brain.
And alcohol??
https://pubmed.ncbi.nlm.nih.gov/29337226/
Mesolimbic = nucleus accumbens. Our ancient brain that is not directly under our control (sounds like cravings???).
And of course….food.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848227/
So…GLP1 is a signal from the gut to the brain to say… "we're all set down here…rachet down the 'seeking', Thank you".
Mother nature likes to multi-task and GLP1 activity appears to bleed into the full spectrum of "cravings". Not just food.
So, how can we naturally boost this activity?
Ozempic is being rolled out en-mass to people just overweight (not with diabetes) now.
Some of this is gut related (expected) but a lot isn't. Very typical with synthetics that mirror natural players.
For example, the side effect profile for synthetic CBD called Epidiodex for seizures is completely different (much worse) than with CBD isolate.
Even synthetic progesterone is very different from bioidentical:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960754/
Okay…33% difference in a cancer risk. Goodness..half of women are on progestins for birth control. We digress.
The point is…can we get GLP1 activity naturally?
Hello Myricetin!
Myricetin is a flavanoid…a class of chemicals that give fruits and vegetables their flavor and/or color.
Quercetin is a common example. In fact, myricetin chemically is like a jacked-up version of quercetin (very similar in structure).
The key point for our discussion:
https://pubmed.ncbi.nlm.nih.gov/28270518/
Ding ding ding!
Look at the effects on glucose as a result of GLP1 activity following use compared to liraglutide (Victoza):
Remember...glucose is the primary signal to GLP1 pathway so it's a good indication of downstream effects.
Interestingly, there's a wide range of effects from myricetin:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395214/
In fact…myricetin appears to protect neurons surrounding…dopamine function!
https://www.sciencedirect.com/science/article/abs/pii/S1756464618301567
Very important for Parkinson's (a loss of dopamine neurons and function).
The most important piece…safety.
https://pubmed.ncbi.nlm.nih.gov/26365525/
They were looking at massive doses:
Standard supplements are around 100mg daily. For a 70kg human.
There may be some interplay with estrogen so test how you feel. Report your results since the effects can be fascinating!
This has been one of the most powerful effects I've personally seen across dozens of different supplements.
Other less potent drivers of GLP1:
https://pubmed.ncbi.nlm.nih.gov/34981502/
Yerba Mate is also a powerful driver of GLP1 and dopamine protection.
https://pubmed.ncbi.nlm.nih.gov/22130241/
Just maybe skip the sugar addition!
This makes myrcitin a key tool in our dopamine rescue toolkit:
Be well. Take care of each other. Take care of yourself.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
Forget allergies...histamine is a monster player for brain neurotransmitters
]]>
We need to talk about histamine
If only it was just about sneezing from ragweed!
Histamine is a powerful force in the brain and body across very different pathways and it rarely gets the respect it deserves.
We found histamine the hard way when full spectrum CBD caused negative side effects but that only prompted the beginning of our journey.
A very tangible signal that our immune system might be hyperactive…perhaps from prior trauma, infection, or stress.
Even in utero or from past generations!
The repercussions of this ramp up is powerful.
The first class of anti-anxiety meds were…anti-histamines! They were actually pretty effective.
The tie between histamine and insomnia is even more telling. It literally governs the sleep/wake cycle with GABA! More below!
Its role in the brain and gut drive powerful effects…both good and bad.
We're going to finally get to know this powerful player and how to range-bound it when hyperactive!
Here are the topics we'll cover:
Let's get started!
We all know histamine as the driver of allergic reactions.
Histamine is released from mast cells, swollen cells of our immune system that receive signals of foreign or bad actors that gain access to our bodies.
Mast cells then "activate" and just spill out histamine plus a range of cytokines…chemical inflammatory assassins.
A slew of effects result from histamine release all tasked with getting bad things OUT FAST!
To the extreme…itching, vomiting, and nausea all push to get foreign interlopers (bacteria, viruses, chemicals, etc) out of the body.
That's just the start!
Mother Nature is all about efficiency and she likes to multitask.
That's where we'll focus!
Histamine is a powerful player in the nervous system and gut. Most people have no idea just powerful histamine is in how they feel and think.
Let's go there now!
Histamine is a powerful neurotransmitter in its own right!
Aside from its immune system's sentry role (the foot soldier), histamine can be thought of as an excitatory agent in the brain.
This makes sense since this general pattern of "revving things" matches its effects on the body.
Something's wrong (intruder alert)...mobilize!
As a result, histamine manages other powerful excitatory players in the brain:
https://www.sciencedirect.com/topics/psychology/histamine
Those are some heavy hitters:
So..we have both the calm and fight players of our autonomic nervous system (background manager).
Then there's serotonin. We'll dive into all of these below.
Histamine's role as an immune sentry in the brain is also critical to the entire inflammatory complex.
All the new research on mental health points to the immune system being hyperactivated and histamine is the first line of defense there.
Here's the rub. The immune system is a one-trick pony.
It responds to psychological stress and trauma pretty similarly to a virus!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733004/
Goodness. Read that back over
Think of when you're really stressed...how that feels. Pretty similar to an allergy attack!
Agitated. Revved up. Flustered. Twitchy!
Below, we'll look at the very powerful effect of early life stress, trauma, or infection on this whole complex!
Neuroinflammation is the enemy of mental health and brain function microglia (brain immune managers) just leak out glutamate, our brain's "gas" pedal.
Check out our review on neuroinflammation.
Glutamate, when excessive, is toxic to neurons in the brain. There are tools to keep glutamate in check which we'll cover and we have a whole review on glutamate.
We've set the stage though so let's go south… its first contact. The gut!
The brain has no real interaction with the real outside world… there are no tactile nerve endings and it sits in a dark, enclosed bony cage.
How does its immune system know there's a problem?
Hello, gut!
If you think about it, our gut has the most interaction with potential intruders with hitchhiking bacteria/viruses hopping on everything we eat.
It's literally the outside world brought in!
In fact, ingeniously, the gut is filled with its own bacteria arsenal, the microbiome, which turns out to be a powerful force in mental health and how the brain works.
Most of our serotonin is made in the gut and other neurotransmitters are directly managed here as well. See our review on probiotics and anxiety as examples.
Histamine and mast cells are big gut players… a form of advance scout.
This is why DAO is such a big deal as it breaks down histamine in the gut but the question is why we have to supplement it?
After all, we all naturally make DAO in the gut. Until we don't. HIT or histamine intolerance.
First...the gut bacteria.
https://www.science.org/doi/10.1126/scitranslmed.abj1895
Hmm. So the gut bacteria act like little foot soldiers to trigger an immune response when they see the enemy!
Check out gut inflammation review or our new review on seed oils.
We're soooo out-gunned!
Now…here's the interesting piece.
The vagus nerve sits at the center of gut-brain communication and new research is pointing to it as a manager as well!
https://journals.physiology.org/doi/full/10.1152/physrev.00043.2007
See our guide on the vagus nerve but understand that it acts like the "brain" for the body and gut. Heart function is directly managed by it which is why your heart will race when histamine spikes.
This is also how the brain gets its "signal" from the front line…the gut.
Let's take a detour further south.
We learned this the hard way. Our founder started having trouble with certain foods, cosmetics, and just about everything mid-40s.
It got worse and worse. She tried DAO, probiotics, and a host of different "fixes" from doctors and naturopaths.
In the end…it was just progesterone.
Progesterone calms the immune response but here's the rub...
Interesting that autoimmune and histamine issues hit women 8 to 1 and creep up during the '40s.
Go figure.
https://pubmed.ncbi.nlm.nih.gov/17166400/
Goodness…it's a break pedal on histamine.
And DAO in the gut?
https://www.larabriden.com/the-curious-link-between-estrogen-and-histamine-intolerance/
We have a whole review on progesterone and mast cell activation.
Interestingly, estrogen has the opposite effect…it boosts immune function. They work in a yin-yang function but progesterone has left the scene mid-late 30's with continuing dropping from there while estrogen stays relatively stable till late 40s.
10 years of histamine hyperactivation!
That's a lot of damage (and symptoms).
A quick backstory. Why does progesterone calm immune response including histamine?
It's a trick nature built in to keep the mom's immune system from attacking the amniotic sac which is actually made by dad's DNA (and therefore…foreign to the histamine system).
Low progesterone is now the key to preemie birth. What happens when progesterone spikes during pregnancy?
For mast cells (and histamine):
https://pubmed.ncbi.nlm.nih.gov/17166400/
"suppressed during pregnancy". Hmmm.
Read our progesterone guide to look at all the interesting effects but histamine is front and center.
Get your hormones tested and support progesterone (bioidentical) as needed. More on estradiol here.
As for testosterone, it wears both hats. Immune modulation. It generally suppresses immune response (and histamine) but can also support it.
Generally…it calms histamine (hence the 8:1 ratio for women and auto-immune)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665824/
Ladies…support progesterone. All our histamine responses to food, etc went away once progesterone was replaced. Everything else is fiddling while Rome burns.
Okay…Let's go back up to the brain.
Histamine can both increase and reduce the function of:
Goodness…that's a who's who in brain function.
To wit...
https://www.ncbi.nlm.nih.gov/books/NBK28245/
Generally, we can think of histamine as being the immune's translator to the brain as an excitability agent.
This all fits with histamine's primary immune response. Ready the forces…we're going to battle.
Nature just gerry-rigged this effect for other results which will become apparent below.
Let's start that journey.
The opposite of excitatory is GABA. GABA is the brain's "brake" pedal.
GABA and histamine (with cortisol) govern the sleep/wake cycle in a push/pull antagonistic effect.
Nothing to do with allergies. Just wake up!
This was the first clue that histamine was a powerful player in the brain.
We mentioned above that immune cells in the brain (called microglia) release glutamate…sometimes too much when hyperactivated.
Glutamate is the directly opposing force to GABA. So…the enemy of my enemy is my friend!
https://pubmed.ncbi.nlm.nih.gov/29858014/
So…histamine drives glutamate (which it borrowed from its immune function) to increase activity in the brain.
We need glutamate, within limits, to run every activity in the brain. It's the true gas pedal!
The problem is when GABA is not able to keep glutamate under wraps.
Let's turn to histamine and sleep (or the lack thereof).
It's been known for a while that histamine opposes GABA to wake us up!
https://pubmed.ncbi.nlm.nih.gov/20851648/
So…Nature took the "vigilance" red alert signal and used a water-down level of it…to make us awake!
Beautiful really.
And GABA is there to keep it in check (unless it's overrun):
Think of the effects of antihistamines. Just look at the side effect profile.
Most prominent: Drowsy
In fact, there are millions of people (mainly women in their 40s and beyond - the steroid loss effect) that use Benadryl or Tylenol PM to get to sleep.
With really dire risk effects later on for dementia and more (we'll cover below).
Simply put..
https://pubmed.ncbi.nlm.nih.gov/20851648/
So…histamine rises during wakefulness and it drops (or stops) during deep sleep.
We did a whole review of histamine and insomnia. In fact, looking at the research, histamine may be THE key.
The net net…histamine when hyperactivates shifts our entire immune "setting" from T1 to T2 and T2 is associated with insomnia.
Check out the review. Very interesting! So maybe that meal DID keep you up at night!
Let's hit another big player…serotonin.
Okay…this is fascinating.
You have two of the biggest brain managers in a ring together: serotonin and histamine.
Serotonin is the manager of ALL human behavior. No hype there. It's a big deal!
Does histamine affect serotonin when released?
It's nuanced.
With normal levels of histamine (like the wakefulness or cognitive activity level), histamine can increase serotonin.
This makes sense…get the motor running and serotonin is the driving wheel.
Now…with inflammation level (hyperactivated) histamine, it's quite the opposite.
Histamine can actually reduce serotonin function.
A fascinating study looked at how inflammation-driven histamine prevented SSRIs (which boost serotonin) from increasing levels:
https://www.jneurosci.org/content/41/30/6564
This also makes sense. Good serotonin levels make you feel…good! Grounded really.
It's a powerful mood and self-esteem manager.
Histamine is our brain signaling agent from the immune system's department (headquarters in the gut??) and if it's detecting danger…that should feel pretty bad.
This begs the question…are SSRIs just calming hyperactivated histamine (inflammation) to raise serotonin levels??
Ummm….
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648163/
We looked at how SSRIs only work when neurogenesis (brain repair) can function but the histamine may be up-river.
It's really about reducing inflammatory load first!
Now…it's gets even more curious.
What about extreme levels of histamine and serotonin?
Serotonin syndrome is actually quite dangerous. Our founder experience it as a result of Lexapro combined with an anti-nausea drug (boosts serotonin) which almost killed her. That whole story of a brutal perimenopause.
Get this…
https://www.dshs.texas.gov/IDCU/disease/tb/forms/PDFS/SerotoninSyndrome.pdf
You can actually get serotonin syndrome from taking drugs that block the breakdown of…histamine!
More on serotonin syndrome but we've seen 3 different responses now!
Read our master serotonin guide…it's so interesting and hyperactivated histamine is the enemy of feeling…well.
In fact, it can feel downright horrible. Let's go there now.
The first class of anti-anxiety meds were actually antihistamines!
Hydroxyzine is the big name and looks at it versus benzos:
https://pubmed.ncbi.nlm.nih.gov/21154375/
But wait…benzos became the go-to for anxiety and they have a nasty addiction effect plus tolerance (see CBD versus benzos).
Maybe…that's exactly why they became the go-to. What a great legal drug market.
Sorry…we're jaded after reading all the research on benzos and SSRIs.
So…back to histamine and anxiety.
First…GABA is our first defense against anxiety (benzos drive GABA till tolerance kicks in).
Histamine directly opposes GABA in the brain.
Remember histamine is a red alert from the immune system…danger! Intruder alert.
Anxiety is actually the correct response to danger. That's its correct use.
Histamine actually drives up our background (autonomic) nervous system to be ready for this.
That's the increased heart rate, blood pressure, etc that comes with allergy response.
The brain picks up on these signals of danger from adrenaline (norepinephrine) and voila…anxiety!
The whole thread through all of this is…stress and our response to it.
Histamine is a powerful foot soldier of this stress cascade:
https://pubmed.ncbi.nlm.nih.gov/10917464/
So…stress spikes histamine in critical areas of the brain.
What about chronic stress?
Goodness.
Think of layers of the stress response:
When these are exhausted, anxiety is there to tell us…Change something! This isn't working.
Histamine is a key signal to the brain from stress of this need to address a danger.
See…mother nature just multi-tasked our allergic reaction player to respond to psychological stress! Very efficient.
We have a deep dive into histamine and anxiety.
Let's turn to medications.
We already looked at how histamine may be the lever that SSRIs use to actually increase serotonin (temporarily) in the brain.
That's just the start!
Many medications directly impact histamine for better and for worse.
Interestingly, benzos increase histamine which is counterintuitive. So they jack up GABA but then send opposite signals via the histamine system.
What about blood pressure meds?
Remember that histamine causes vasodilation…more room in your veins equals less blood pressure.
https://pubmed.ncbi.nlm.nih.gov/27191340/
So blood pressure meds.
First…the beta-blockers like metipranolol.
https://bjo.bmj.com/content/84/9/1004
Okay…so these medications jack up histamine (which we know drops blood pressure) but…because they're toxic! The body is trying to get rid of a poison!
Seems to be a bad trade-off.
The next big class…ACE inhibitors?
https://pubmed.ncbi.nlm.nih.gov/2474161/
Angiotensin indeed.
Remember…histamine has direct effects on the entire cardiovascular system!
Let's now zoom in on the disease-du-jour.
First, we'll set the table.
Histamine Intolerance (HIT) is meant to describe an inability to eat certain foods due to their histamine content.
This is largely attributed to a reduction in DAO and a plethora of "products" to address this from DAO supplements to pig kidney extract to very strict histamine diets.
After all, any "real" food starts to break down almost immediately and histamine is there to respond to bacteria and decay, right?
Aged meats, cheese, fermented food, etc.
Okay…here's where we get angry. Let's look at powerful clues of what's really driving the train.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308327/
Just a head's up…the DAO levels (supposedly the main driver) are the same in men and women despite women getting hit much harder.
So....
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746020/
Goodness. Ladies, your progesterone drops by 50% by age 40. And continues down.
Our founder was on the DAO, porcine kidney, etc merry-go-round. After bioidentical progesterone replacement, she can eat whatever she likes. Peppers, etc that were unheard of 5 years ago.
Her story is here but progesterone is THE immune calming player and HIT is just a part of this.
Check out the progesterone guide to see why this is just the tip of the iceberg.
So…why not just take anti-histamines like Benadryl or Tylenol PM?
Researchers realized much later that classic antihistamines have a serious knock-on effect.
They rip acetylcholine.
This is a critical neurotransmitter - our "calm and focus" player released primarily from the vagus nerve.
It's the opposite of adrenaline if that gives you an idea of how it feels. Check out our vagus nerve guide or acetylcholine guide.
Huge player for:
Let's zero in on the dementia risk.
This is longer term and revolves around the older class of anti-histamines.
Acetylcholine naturally decreases as we age so…let's not jumpstart that.
https://pubmed.ncbi.nlm.nih.gov/25445036/
So…are there ways to calm histamine response that don't build tolerance or have knock on effects?
Let's turn there now.
Here's are histamine toolkit:
We have deep dives on all of these but here is a quick recap.
The prerequisites:
Okay…that leaves a few options. Here they are.
The highlights…
Mag is our first line mineral stress response buffer and this includes histamine:
https://pubmed.ncbi.nlm.nih.gov/6445415/
Stress just eats up mag so it's all intertwined!
Full review of magnesium here. We use this one here.
CBD has powerful effects on histamine and the immune system generally! This gets to the root of the issue where early trauma, stress, and infection can upset the apple cart later in life.
CBD's effect on histamine is more sophisticated…it directly acts on mast cell activation which calms the histamine explosion when hyperactivated!
The 'when hyperactivated" is critical as histamine is essential to normal, wakeful functioning.
That's why we don't see the drowsiness and other issues as with anti-histamines.
The technical piece (we'll translate):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433789/
So…CBD triggers an anti-inflammatory pathway called PPAR which boosts other key elements that "resolve" histamine release. Pushes back the other way!
See CBD and asthma or CBD and mast cells to learn more.
The 2000mg level (one dropper is around 70mg) is a good place to start but we have a Top 10 Tips for Calming Mast Cells with more guidance.
Get your levels tested:
The Dutch Test is the gold standard but blood tests at least show trajectory over time.
For women in their 40's and older, this is THE critical piece. Progesterone directly calms immune function...and it's dropping.
Must be bioidentical as synthetic hormones have side effects that bioidentical don't.
If your doctor doesn't know or care about this…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960754/
Just a head's up…the immune system governs cancer (see cancer guide)
Prometrium is bio-identical progesterone. Estrace is bio-identical estradiol. Both are oral and we looked at the whole oral versus topical below.
Speaking of steroidal hormones!
D is a steroid we get from the sun…a major manager of immune response. And histamine which comes from mast cells?
https://pubmed.ncbi.nlm.nih.gov/27998003/
Goodness…low D and mast cells just run amok.
Their conclusion:
So many people are deficient and endocrinologists want us closer to 60 ng/ml (not the 30 RDA limit for deficiency).
We have a whole review on Vitamin D. Get tested!
Medicinal mushrooms (all mushrooms really) are fascinating for balancing our immune response.
Just a few examples.
Chaga has a direct effect on histamine response as shown in studies on food allergies:
https://pubmed.ncbi.nlm.nih.gov/29175507/
To translate, in live bodies, Chaga components were able to stabilize mast cells (calm histamine) and shift the immune setting to less inflammatory!
Remember…the gut sets our general inflammatory and histamine setting for the rest of the body and brain.
We could go on and on…check our big review on medicinal mushrooms and immune function.
We use this one which has a blend of the most popular mushrooms species.
Remember, PEA is a backup endocannabinoid in the body. Called-in reinforcements.
PEA is a big wet blanket for histamine response when excessive!
For example, with asthma (an explosion of histamine and inflammatory agents):
https://www.frontiersin.org/articles/10.3389/fphar.2017.00857/full
We have a big PEA guide and we use this one here when needed.
Okay…that's a wrap. A series of tools that don't build tolerance, addiction, or rip acetylcholine or other key pathways!
Let's get to the real exciting news though. Getting to the root of why our histamine response might be hyperactivated (outside of the loss of steroidal hormones).
At first, it sounds depressing.
Our histamine response may be nothing more than remnants of early trauma, infection, or chronic stress.
In utero, during times of development, or even past generations!
This early interaction causes our immune system to hyperactivate throughout life. Little "mark ups" that affect our histamine setting…for life!
This is especially true in the brain, nervous system, and…gut:
https://pubmed.ncbi.nlm.nih.gov/32996781/
The research is really pointing to this being the root of mental health issues generally and mast cells are just a great signal for immune hyperactivation.
A study on early life stress and anxiety or depression:
We have big reviews on immune system and mental health or CBD and early trauma.
So…great…the die is cast!
Not really…these "markup" to our immune system can be "edited". We looked at that process here.
Medicinal Mushrooms, Psilocybin, and CBD isolate are key players in this rewriting process. Very exciting times!
Check out our related research and please…give histamine the respect it deserves!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
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A look at serotonin rescue, prolactin control, and repairing the brain!
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It's finally hitting the front pages. Post SSRI Sexual Dysfunction.
We've been covering the issues around tampering with the all-powerful serotonin pathways at our problem with SSRIs review or how we tapered off of SSRIs.
Lexapro was prescribed for our founder and it almost ended her. Total lack of feeling of anything (including sex drive) which ended in 3 nights of no sleep and an ER visit.
We'll touch on exactly what's driving the flattening of feelings including libido below but more importantly, we'll look at tools to repair.
The focus will be on neurogenesis (literally building new brain connections) since it's at the heart of any possible repair.
There's also a question of steroidal hormones to address as SSRIs are prescribed earlier and earlier…during key periods of brain and body development.
This is tricky since research shows developmental changes in serotonin function with SSRI use during these periods (up to age 25 in the case of puberty-driven brain development).
Wait till you see big sexual wet blanket of prolactin below!
Green shoots are appearing and we'll look at them along these topics:
Let's get started!
Serotonin is the master manager of ALL human behavior. We did a deep dive on serotonin specifically here or serotonin and self-esteem.
Fascinating research!
Libido is just one facet of that giant canopy of behaviors.
The problem is that SSRIs build tolerance.
This means that they are hitting the serotonin pathways and receptors too hard relative to our natural levels and that's assuming you had low serotonin function to begin with (they can't test brain levels).
As a result, the body/brain will start to push back and actually reduce serotonin receptor numbers and sensitivity longer term.
This is at the heart of the issue for short/mid-term serotonin dysfunction (or lack thereof).
Some people though are seeing flat affect (the technical term…not feeling anything) for years after!
Technically, the receptors should start to come online about 30 days after discontinuation.
The DNA that makes proteins to form the receptor literally needs to be turned back on.
With PSSD, this isn't happening. Why?
The best theories are a few-fold:
We'll look at all of these and how to offset the effects.
The development piece is really driven by age of use (in utero, age 2ish, puberty through age 25).
This is a real issue and luckily, the brain is always changing and we'll look at how to boost that process.
So how prevalent is this?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034069/
Now magnify this by the # of prescriptions…especially for teens when serotonin is actually building out its future system!
https://psychnews.psychiatryonline.org/doi/full/10.1176/appi.pn.2017.pp9b2
That's pre-pandemic! It's only gotten worse and look at the teenage range (we'll explain why this is important below).
The brain doesn't stop developing until age 25 (with white tract matter continuing a decade beyond).
Okay…that's the bad news. Let's start to unravel the PSSD piece.
Let's first address each of the three items above.
First, do no harm.
You can't bring serotonin back online without removing the ball and chain from prior trauma, infection, and stress. Especially in early life or in-utero.
Don't take our word for it…
https://pubmed.ncbi.nlm.nih.gov/32981537/
Goodness…serotonin is behind the curtain in managing our response to future stress.
Other research shows serotonin function can actually be downregulated as a result:
https://www.frontiersin.org/articles/10.3389/fnmol.2014.00024/full
Here's the key takeaway…serotonin is a powerful stress response buffer.
In fact, it's a buffer for pain, stress, infection, and more!
We've covered this in-depth in our trauma review on how the immune system is the future of mental health.
If your system has been "edited" by past stress (trauma and infection work the same way), this has to be addressed or your serotonin system will never function correctly.
Interestingly, this may be why you were prescribed SSRIs, to begin with.
The fascinating piece is that a great deal of this "markup" is done in the immune system and we'll look below at how to edit this out!
Very exciting times.
Let's take a quick detour to what researchers have known for some time about SSRIs and libido.
You may get a little angry (at least we'll feel something, right??).
Why the sudden explosion of media coverage around PSSD? Did they just find out about this effect?
No!
Two fascinating examples.
SSRIs have been used off-label for years now with premature ejaculation for males.
Specifically, delaying it and numbing the orgasm response.
Placebo, double-blind study looked at 100 men with premature ejaculation. The results?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374931/
AIPE is a score for PE.
Ummm…100%? You rarely see that number outside of election results from dictators.
We have a huge study on orgasm here and even premature ejaculation.
With SSRIs, it goes deeper.
SSRIs have been used in prisons to reduce the "activity" of sexual predators in their system.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176659/
So…it's been known.
The fascinating piece is this.
When they're studying SSRI sexual dampening effects as a primary outcome (intended like above) versus a side-effect, roughly 70% of the people see a significant outcome.
Now…compare this with the estimate for people who see a benefit on SSRIs…
30%!
The mirror image. Mostly, people with severe depression.
We'll see below how the sexual effect may be due to too much serotonin which makes sense based on the 70/30 split.
For 70% of people taking SSRIs, serotonin was not the issue! Hence the hyper-serotonin PSSD effect.
We did a deep dive into the SSRIs research. They can't test your serotonin levels by the way. All guesswork is based on symptoms.
We'll assume you're not in prison…what's driving this with SSRIs and then we'll look at how to reverse it.
Let's first turn to a significant support system for serotonin.
We have to get past the thought that steroidal hormones are just about reproduction. Couldn't be further from the truth.
Libido…for both men and women is driven by estrogen! Aggression is driven by testosterone.
Either way, steroidal hormones are key to serotonin function.
Just look at estradiol's (our primary estrogen) effect:
https://www.zrtlab.com/blog/archive/mood-menopause-perimenopause/
We learned this the hard way during perimenopause (that story is here) which is how the SSRI prescription originally hit us.
Get your levels tested. There are lots of estrogenic signals in our food, environment, plastics, etc.
It's hard to get serotonin back in play without first balancing the supporting cast (estradiol or testosterone).
Look at the 2nd item.."helps augment serotonin receptor activation"
Hello! That's literally what we're trying to do. Undo the tolerance effect of SSRIs!
This is definitely part of how early life stress is "transmitted'"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850073/
Essentially…early life stress can alter estradiol function long term.
Early life stress actually increases testosterone (and aggression) and stress hormones.
Interestingly, flux in estrogen is what feels so bad (anxiety, depression,etc). Remember…serotonin likes to be range-bound. Too high is almost worse (see serotonin syndrome) than too low.
Flux in estrogen directly affects our ability to handle…stress:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764412/
Is there a gender connection between these estrogen flux effects and SSRI prescriptions during puberty (teenagers)?
https://www.statista.com/statistics/1133612/antidepressant-use-teenagers-by-gender-us/
Goodness…what are we doing to our girls??
It's better to evaluate hormone flux than try to monkey-hammer the manager of ALL human behavior.
PSSD can affect people of all ages but starting SSRIs early definitely carries some risk.
Let's look at that piece now.
Studies on mice who are exposed to SSRIs are fascinating.
Remember…the gut has its own "brain" - the enteric nervous system with the most neurons outside of the brain.
Over 90% of serotonin is actually made in the gut!
Here's the fascinating piece…serotonin during development directly manages the build-out of…our serotonin system!
https://pubmed.ncbi.nlm.nih.gov/11750793/
So what happens when those mice are exposed to SSRIs?
Their gut nervous system doesn't develop fully. Reduced receptor numbers and function.
As a result, you see a slew of gut and brain-related issues. Dr. Attia has a great podcast on these effects here.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963518/
This system's version of insulin tolerance.
Remember…the brain is being wholly remodeled during puberty…the prefrontal cortex (what makes us human) is being built out and "adultified".
Serotonin is front and center as the architect.
"Reduced serotonin tone later in life"
This is a real issue since development is an explosion of gene-directed growth. We'll look to see if we can crank up the brain-building machinery below.
Other signals are there for the brain as well:
https://www.nature.com/articles/s41598-021-81327-z
Let's now turn south…to the local player.
Serotonin is a huge systemic player in the brain, gut, and nervous system.
With PSSD, there's also a local aspect as well. Apathy may reside in the brain but "profound genital anesthesia" is local.
There's an important nerve structure that supports our entire pelvic floor in either gender which directly governs sensation including sexual touch.
So….to set the stage.
Imagine an oncoming bus barely misses hitting you. You jump out of the way thanks to your fight-or-flight autonomic nervous system.
The last thing on your mind…is sex. In fact, good luck while jumping out of the way thinking about anything remotely sexual.
The current theory on the pudendal nerve and SSRIs is that this system is blunting activity in the nerve trunk which manages sexual arousal locally.
How to make sense of this since the goal of SSRIs is to go the other way (rest and digest)?
Let's look at the key player in our "rest and digest" system. Acetylcholine (guide here).
This is your calm and focused player. The Vagus nerve is a major site of production.
So…SSRIs effect there??:
https://www.researchgate.net/publication/44653848
Okay…this is bad news. Acetylcholine is key to dementia and ADHD risk among others.
Does that bare out with SSRIs?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079596/
And ADHD (along with autism):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686301/
Acetylcholine (sympathetic nervous system) directly opposes Adrenaline (parasympathetic nervous system - jump away from bus).
Could we be chronically stuck in a fight-flight pattern that is just hammering sexual function?
Interestingly, it's hard to find research on SSRIs and pudendal nerve activity. Go figure.
We do however have research on another powerful player. Prolactin!
If we were betting people, we would wager here.
Prolactin has many roles but one of them is to just hammer sexual desire, function, and activity.
It's the basis for the "refractory" period after orgasm during which a male is unable to get an erection.
The effect is not just for men though..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901097/
Sound familiar?
So…what about SSRIs' effect on prolactin?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440440/
Ding ding ding!
We can drop the mic now. "Hyperprolactinemia".
Prolactin levels so high as to be associated with a disease state.
This speaks to why SSRIs can have a pretty immediate effect on sexual desire and function.
This level of prolactin may also indicate too much serotonin!
After all, they can't test your serotonin levels during that 10-minute visit they prescribe the SSRIs (sorry…jaded).
Either way, too much prolactin is a giant wet blanket on libido and sexual function not to mention orgasm.
Just a final wrap…
https://www.jneurosci.org/content/jneuro/36/28/i.full.pdf
Okay…that's all the bad news. Let's change course.
We're going to focus on a few key areas with a focus on CBD and other tools:
This is the best-known approach to healing after drug tolerance effects such as with SSRIs, MDMA, ecstasy, and finasteride (yes…issues like PSSD as well).
Why CBD?
It hits all of these key pathways but a fascinating review on PEA (another endocannabinoid) sets the stage (more on that in the pudendal nerve area).
Let's get started!
Long-term SSRI use leads to reduced serotonin function. This is tolerance and it's the enemy.
Keep in mind that serotonin can be exhausted or downregulated by the usual suspects:
We've looked at this at our CBD and stress or serotonin and infection reviews.
So…check this out!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
To translate…an injury caused exhaustion of serotonin which led to pain and anxiety.
CBD countered this by "rescue" of the serotonin (5ht) pathway!
Here's the critical piece...CBD is a positive modulator of serotonin.
It supports when low!
We don't see serotonin syndrome or the bizarre symptoms that come along with SSRIs or too much serotonin (insomnia, etc).
In fact, serotonin syndrome is a result of the hyperactivation of histamine!
You can actually get serotonin syndrome from drugs that block the breakdown of histamine (no direct serotonin effect needed).
CBD doesn't display this even at very high doses tested (1500mg daily and higher).
Check out CBD versus SSRIs to learn all about powerful differences.
In our how SSRIs really work review, we dug deep into the process and BDNF and neurogenesis was the key driver!
Let's go there now with CBD.
First, some good news.
Serotonin nerve pathways can repair but it takes time (assuming we've taken the burden off the existing system from the above insults):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990493/
A key piece of this is BDNF, our brain's fertilizer:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772430/
5-HT is code for serotonin!
CBD's effect on BDNF and neurogenesis:
https://pubmed.ncbi.nlm.nih.gov/29869197/
Goodness. CBD directly supports BDNF and brain repair…in this case, the prefrontal cortex (a hangout for serotonin), the key hub that keeps fear at bay and makes us human.
Check out CBD and BDNF.
Other powerful BDNF players:
You're going to see this list over and over.
Let's turn south to steroidal hormones.
There's no workaround for testosterone, estradiol, and progesterone.
We have massive reviews on the health effects here:
Bioidentical is critical and testing is required. If you're older, beware of the "your levels are fine for your age" dismissal.
Find a good naturopath who wants to actually understands the power of steroids.
Vitamin D is a steroid that governs about 1000 transactions and helps to manage the other steroids.
So many people are deficient and endocrinologists want us up to 60ng/ml.
Then, there's the question of hormone flux. Remember, it's the change in estradiol that causes so much suffering.
Berberine shows interesting effects for balancing hormones such as with cases of PCOS (polycystic ovarian syndrome). An issue with pretty intense hormone imbalance and a new bacteria angle from recent research.
Check out the review of berberine.
B vitamins and Omega 3's are also crucial to hormone balance and of course, a constant stream of estrogen from our food and environment isn't helping:
Get your levels tested (not sure why this isn't part of the annual anyway) and for men, T has dropped at every age range by roughly ½ in the last 20 years!
See the testosterone review….just crazy data!
Let's turn specifically to the pudendal nerve.
Okay…this is both fascinating and a great excuse to introduce the endocannabinoid system in which CBD operates.
First, the endocannabinoid system is tasked with balancing other key systems in our body…maybe every system:
Alright…so right in the wheelhouse of repairing our systems.
CBD works like a feedback mechanism unlike THC (its plant-based cousin) which pushes in one direction (hence the "high", side effects, and tolerance longer term).
So…let's introduce a distant cousin…PEA. Short for palmitoylethanolamide (thank goodness).
Studies are starting to look at PEA for pudendal neuralgia:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645590/
This speaks to to endocannabinoid system being front and center in...repair!
Another study looked at CBD and neuropathy (essentially…damage nerve tissue usually from too much glutamate):
https://pubmed.ncbi.nlm.nih.gov/31793418/
So between nerve repair (BDNF) and nerve recovery (neuropathy), there's exciting research towards pudendal nerve function IF the issue is mechanical and not upstream signals like serotonin and prolactin.
We'll touch on that below. Big review on PEA.
Next stop..north to the gut.
We can't really discuss serotonin without looking at the gut.
Inflammation there is a huge hit to serotonin function thus the diarrhea, nausea, or constripation, etc which result from serotonin imbalance.
CBD has a powerful effect to counter imbalance there!
Since the endocannabinoid system is varied and far-reaching, CBD's interaction in balancing gut states is as well:
https://www.frontiersin.org/articles/10.3389/fncel.2022.867267/full
Okay…catch the last one! Serotonin.
We have massive reviews on CBD and gut inflammation.
Also, berberine, Vitamin D, steroidal hormones, and medicinal mushrooms are powerful players.
Let's turn to that prolactin piece (that's where our bet is).
First, do no harm. Does CBD drive prolactin?
https://pubmed.ncbi.nlm.nih.gov/8257923/
Just a head's up…can't say the same for THC (cannabis):
https://www.frontiersin.org/articles/10.3389/frph.2022.820451/full
An increase in prolactin (wrong direction for libido). Cannabis smoke is estrogenic but blocks aromatase (which drives male libido in the brain).
Alright…so what about getting prolactin back in balance (too high with SSRIs)?
This is so interesting!
Let's introduce cortisol, our primary stress hormone.
First, cortisol and prolactin have a direct relationship.
To wit...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304861/
This makes sense…if you're under stress (discount danger basically), not a great time to reproduce.
Remember…hyperprolactinemia means too much…to a point where it's abnormal.
So…stress control is critical. CBD's effect there?
Check out the review of CBD and public speaking…for people with diagnosed social anxiety! A form of stress torture really.
The net effects of 600mg 1 hour before:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/
Goodness.
Big review on CBD and performance anxiety or CBD and stress response but it goes deeper.
When SSRIs are first started, there can actually be an INCREASE in anxiety and depression.
What gives?
Turns out that serotonin being so far-reaching can increase corticotrophin-releasing factor, the initial trigger for stress (cortisol, etc).
SSRIs will actually boost our stress response initially!
CBD and corticotrophin-releasing factor?
https://journals.sagepub.com/doi/abs/10.1177/0269881118805495
Why interestingly?
Because it didn't have this effect under times of low stress!!! Remember…feedback mechanism when pathways are taxed.
Keeping prolactin under wraps requires balancing cortisol and stress pathways.
Some usual suspects on the stress response front:
Let's get practical now. How much? What type? Etc.
First, peak neurogenesis guides our dosing regimen for CBD.
300mg daily matches that level in research.
There are higher doses for more severe issues but brain repair peaks at 300mg.
Over time, this level can come down but check out our review for how to increase bioavailability by up to 4xs.
Next up is the type of CBD.
CBD isolate (CBD by itself) is very different from full-spectrum. Aside from all the research being based on CBD by itself, histamine is the big player with PSSD.
Remember that the excess of SSRIs can actually occur due to histamine being boosted!
CBD isolate calms histamine response when excessive (see CBD and histamine or CBD and brain inflammation) but full spectrum can actually trigger responses.
We see this all the time when people see their anxiety go up with full-spectrum.
More on CBD isolate versus full spectrum or check out product reviews to see people's actual histamine response.
Certain requirements are mandatory for CBD generally:
Then, there's cost.
We price our 6000mg bottle at 2-3 cents per mg of CBD before discounts of up to 50%.
We found CBD after a brutal experience with Lexapro and serotonin syndrome (that story is here) following perimenopause (when estrogen goes sideways! - go figure).
If we can help other people avoid what we went through, it's worth it.
To that end!
We've covered the big pathways and CBD's effect there.
It's not the only player! Here's our PSSD rescue toolkit:
We have giant reviews on most of these because they don't build tolerance (enemy #1 with many supplements) and address the key pathways mentioned above! You can search top of the page for any of these guides.
Look…our experience with Lexapro opened up an entirely new world to us regarding our health and wellness.
You have to use this horrible experience to learn and build back even stronger!
Be well. Heal. Get back to health.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
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It's actually a smaller percentage of people that get stuck using THC or cannabis too heavily.
Estimated at 8%.
We have a whole review on whether hyperactive brain activity from glutamate and inflammation is driving heavy use but, we're going to focus on tools that help taper use.
Tolerance is definitely a thing with THC as it hits CB1 receptors in the brain too hard and for too long compared to the natural player, anandamide.
As a result, the body pushes back and will actually reduce CB1 receptor numbers and activity.
This feels pretty bad since anandamide is our primary stress response buffer…a big wet blanket in the brain!
After all, anandamide is named after the Hindu goddess of bliss!
Examples of its action:
It takes at least 30 days for the DNA to be turned back on in order to restart our natural CB1 activity so the question is…
That's what we're covering here! Based on hard research.
Our Top 10 List for Tapering THC
Let's get to it!
When you first started really using cannabis, did it go something like this?...
"My brain was running too fast. Repetitive thoughts. Worries. Pot just slowed things down so I could breathe"
Got your attention?
We have a million+ words and 1000's of hours of NIH research across the site.
One element keeps coming up again and again.
Early life stress, infection, or trauma can set off a chain reaction across the brain that continues for life (we'll look at how to reverse this).
It can even be in utero (especially 3rd trimester or preemie birth) or from past generations!
This "markup" occurs in our epigenome, a system layer just on top of our DNA which determines which genes are turned on, how long, and how much!
Most of the activity happens specifically in our immune system genes. Inflammation. Brain inflammation in our case!
Huge implications from this:
We have deep dives on each of those but this speaks to two main results:
This quickly causes anxiety, depression, and a range of issues.
Anandamide is our backup stress response buffer when everything else is failing. The problem is that it's created as needed and broken down almost immediately.
THC isn't. This causes the pushback but if we're going to taper cannabis, we have to not only address this withdrawal but also why THC felt so good, to begin with.
We have to calm the immune system (inflammation) which just gushes out glutamate (the brain is red-lining the engine).
Look…we're ALL dealing with some baggage. I changed schools every 2 years. My spouse has dyslexia (school was a literal torture). And worse!
That "stuff" is etched into our basic machinery….now! Cannabis was just self-medication.
Most of what we see below goes after that piece and/or makes the transition (tolerance) easier.
Check out the immune system and mental health or how to rewrite your mental health past.
Here's the general cause and toolkit (don't worry...we'll go through it all below):
Let's get real practical first.
Cold turkey is not advised with heavier and longer term cannabis use.
Remember, THC slows things down and the brain will actually ramp up glutamate (the opposing gas pedal) to counter this.
With enough use, stopping cannabis immediately can result in seizures (a rush of too much glutamate) as a result.
We're all out of balance!
So, it's recommended to slowly taper down the level of cannabis over a minimum of 30 days but maybe even 2-3 months depending on how you feel and how much you support with the options below.
If you're trying for the 30 day period, slowly dropping 25% a week is a good estimate but adjust according to how you feel and situational changes (periods of stress, etc).
We're going to directly support the key pathways with tools that don't build tolerance while also trying to "edit" out the prior markups from early life stress, trauma, and/or infection.
The initial 10 days can be the worse depending on the tapering schedule but studies show that 30 days is the point where CB1 receptors come back online after NO use.
We need to address the effects of THC withdrawal!
That's our goal.
Let's turn to the tools to make this much much easier.
We have a full review on CBD and THC addiction or withdrawal.
While THC directly spikes CB1 activity, CBD supports CB1 in a feedback mechanism.
It boosts CB1 activity…when low! A safety net. Exactly what we need when tapering.
It does this by blocking FAAH, the pathway that breaks down anandamide.
This is all about getting our natural anandamide function back online but:
CBD is really the first line of defense for THC or cannabis misuse. In fact, the "entourage" effect really speaks to how CBD counters many of the excesses of THC.
See CBD versus THC here.
In fact, studies in the brain show how CBD will counter the brain remodeling that occurs from THC..especially if you used it in your teens.
More importantly, it directly supports GABA and serotonin while calming stress response and glutamate!
For our taper schedule, studies on opioid withdrawal had a split schedule:
The 600mg is for bad withdrawal symptoms and to keep glutamate at bay.
The 300mg actually speaks to the process of brain repair called neurogenesis!
This is the key to longer term healing and rewiring of addiction circuitry.
Finally…the medical community has caught up:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116091/
The 400mg level was the most effective…again neurogenesis is really key to brain repair (the 300 level from above).
Check out the full review on CBD for THC withdrawal and use the FIRST50 discount code on the 6000mg bottle. A full dropper is 200mg. After meals and hold under the tongue for up to 60 seconds to boost and speed availability.
Next up…the mother of all hormones has a special trick.
Here's the pathway for both men and women:
Progesterone drives GABA (the brain's "brake" pedal) and estrogen/testosterone drives serotonin (primary stress response buffer).
We'll cover steroidal hormones below because they may be a key missing piece but preg has another trick up its sleeve with THC.
Pregnenolone is our brain's natural "greening out" player.
When THC hits the brain, our body tries to counter its excess with pregnenolone.
Don't take our word for it!!:
https://www.clinicaltrials.gov/ct2/show/NCT02439814
"Inhibits drug-seeking behavior". What???
This is ground zero for what we need right now.
You can easily supplement pregnenolone while eating good fats (learn why the type of fat is so important to brain function and inflammation).
We have a massive review on pregnenolone but know that THC use is slowly eating up your steroidal hormone pipeline. Pregnenolone steal.
Check out estrogen and mental health or our testosterone guide. You don't want to rip our primary repair/replenish pathway!
For preg, the standard dose was from 30mg to 90mg daily and we use this one.
Let's turn to another cannabinoid. This time, one that is already in your body.
We avoid CBG, CBN, delta8, and CBC because they push pathways in one direction…so just a different (albeit slower) form of tolerance.
PEA however is fascinating.
It's a backup to our back-up (anandamide) in times of stress and tapering is definitely stressful.
But what matters for us:
https://pubmed.ncbi.nlm.nih.gov/23896215/
Of course, it does…directly supports our natural endocannabinoid system which THC is juicing up.
Most importantly:
A great tool for tapering cannabis and THC.
The dose ranges from 300-1200mg daily and we used this one. The safety profile is strong (or we wouldn't include it).
Okay…now some very exciting news from the obesity field with a focus on dopamine (reward circuit).
There's a great deal of buzz right now around anti-obesity drugs called GLP1 agonists such as semaglutide (Ozempic). It runs around $30K annually and requires injections.
A fascinating 'side effect" of this class of medication is a reduction in heavy alcohol use and a reduction in other drug cravings (cocaine, amphetamine, nicotine, and….THC!)
Newer research is showing how this gut-based molecule (GLP1) not only drives food cravings but directly affects the circuit for all cravings!
Hello Dopamine!
Now..what if we can affect the same pathway with a natural and very safe option?
Hello, myricetin! Myricetin is a natural plant material found in red wine which is very similar to quercetin (see our fisetin review).
https://www.nature.com/articles/aps201450
Here's the key piece…myricetin appears to balance the dopamine system and reduce cravings!
Myricetin boosts GLP1 and this is at the heart of its effect:
https://www.frontiersin.org/articles/10.3389/fnbeh.2020.614884/full
People…this may be the most exciting new research since…CBD research!
The safety profile of myricetin is very strong and its effects build in 2 weeks. We have a full review of myricetin because the effects are profound and far-reaching.
Let's address a key pathway that may be outgunned.
We have massive reviews on:
There's no getting around their power to address everything we're talking about.
They are the dam that holds back the damage from stress, inflammation, and everything that's ramped up from early stress, trauma, and infection.
Forget reproduction and libido.
We're talking brain repair!
One example…of thousands.
Estrogen directly drives serotonin, our primary stress response buffer.
In men, testosterone is turned into estradiol in the brain via boatloads of aromatase so…same effect.
Serotonin has a side hustle though…it directly drives BDNF, our brain's fertilizer.
Here's the rub…if we have stress and brain inflammation, the result is excessive glutamate which is toxic to neurons.
We looked at how THC may be an immediate port in the storm of glutamate in the brain.
BDNF is tasked with cleaning all that up! It's losing the battle after the priming from early stress, infection, or trauma.
More importantly, BDNF rewires the brain…including the pathways of addiction!
To "overwrite" this, we need BDNF and in fact, some drugs will dampen BDNF which is why addiction so hard to beat.
And THC….
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433615/
This is tolerance! It's why it can be so...hard...to....change.
So…get back to the basics. Check your steroidal hormone levels.
There's a clear gender difference with cannabis use disorder:
https://www.sciencedirect.com/science/article/pii/B9780128007563000156
Now go read our testosterone guide to see how T levels have dropped over the past 20 years across every age band!
Like almost in half.
Then…go read our fats review to see one big reason why.
Low T is practically epidemic as we're swirling around in estrogenic effects (food, plastics, seed oils, etc).
Women are not immune and too much estrogen counters progesterone which calms inflammation and supports GABA, our brain's brake pedal.
Get your levels tested. Support as needed with bioidentical with your naturopath/doctor.
There's no "band-aiding" poor steroidal hormone function.
Also…get your Vitamin D levels tested. D is a steroid we get from the sun with powerful effects on everything we've discussed. Quick update...we're no longer in the sun like our ancestors!
Endocrinologists want us at 50-60 ng/ml and many people are deficient!
This entire steroidal hormone complex has to be addressed!
There's clearly a strong connection between steroidal function and cannabinoids:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212868/
Let's turn to that "fats" question.
We have a massive review on how our fats have been substituted over the past 40-60 years much to our chagrin.
It's primarily about the ratio of Omega 3 to Omega 6!
Omega 3 (think fish oil) is anti-inflammatory while Omega 6 can be inflammatory when excessive.
The brain and nervous system are especially susceptible to this effect.
Two interesting aspects from both a cause and cure angle.
First, omega 3's do much of what a person originally got from THC (before tolerance kicked in):
https://www.sciencedaily.com/releases/2017/07/170718142909.htm
See…originally you were coming for the anti-inflammation in the brain but then staying for the addiction and drop in natural levels (tolerance).
Omega 3 fats are a cleaner way to offset this loss of cannabis.
In fact, Omega 3 shares a key pathway with cannabinoids in the brain that directly balances dopamine (the addiction piece) function:
https://pubmed.ncbi.nlm.nih.gov/33108021/
To translate the Klingon...CBD and Omega 3s stimulate a pathway called PPAR that balances dopamine function and keeps the brain...level.
There's a percentage of heavy cannabis users that are using THC to keep dopamine suppressed in an older brain region to calm a host of bad symptoms from hallucinations, paranoia, extreme anxiety, and agitation, etc.
In fact, people with schizophrenia actually have elevated anandamide levels…the brain is trying to offset this dopamine imbalance.
The old theory was that cannabis raises schizophrenia risk. The newer research is indicating that people with high risk are using cannabis to self-medicate...but eventually making their situation worse due to tolerance.
Omega 3s target this key dopamine pathway at the heart of a range of pretty serious symptoms.
CBD also directly calms this imbalance (see CBD and psychosis).
By the way, anandamide is a fat itself! Check out the fats article (eye-opening) but Omega 3's are a great tool for tapering THC.
Let's turn to that glutamate (gas pedal) piece.
Many people we talk to express that they like cannabis because it slowed down their racing thoughts.
Of course, tolerance builds and that actually goes the other way with time but are there ways to calm glutamate and bring the brain back to balance?
We need to introduce GABA, the "brake pedal" of the nervous system. It directly opposes:
Balancing GABA and glutamate may be key to this whole process.
Everything above helps here (big shocker) but there are two other key tools that are safe.
Magnesium glycinate is our metallic stress response buffer.
Mag directly supports GABA and the glycinate allows it to cross the blood brain barrier better.
We have a massive review on magnesium glycinate for anxiety, sleep, and inflammation.
Mag function is front and center:
https://pubmed.ncbi.nlm.nih.gov/30714574/
Hmmm… stress and trauma. It's outgunned!
Most importantly for tapering cannabis, it keeps glutamate under wraps:
We take 100mg 3-4 times daily (great before bed). Super safe and a great tool for tapering and just mental health generally. We use this one.
NAC is another great player with a different pathway. NAC acts like a glutamate "sink" when excessive.
It also supports our detox pathway called glutathione.
Here's the key piece..
https://www.sciencedirect.com/science/article/abs/pii/S0306460322000491
CUD - cannabis use disorder.
We're not surprised. Again, the net effect of brain inflammation from early trauma and/or poor steroidal hormone repair…is damage from glutamate!
Have to turn off that firehose and NAC is a powerful lever there.
Extensive review on NAC and addiction or mental health (same thing really) and we use this one.
Finally…addressing the original sin.
It could have been a complicated birth. Maybe influenza in 3rd trimester. Maybe trauma at age 5. Social isolation at age 13. Traumatic injury at age 21.
Take your pick, it's hard down here.
The brain is a prediction machine at its core… making sure bad stuff doesn't happen to us…again.
Vigilance goes up. Fear goes up. Inflammation (immune system) goes up.
And stays up. Never…ever…let that happen again.
We have to edit this out of our "code" and most of that info resides in the immune system.
How do we know?
Psilocybin (from magic mushrooms) is about to revolutionize mental health. We have a massive review here.
Wow! Effects on anxiety, depression, and a range of mental health issues come from changing the markups to our immune system.
Let that sink in. This means we can edit out the effects of past trauma!
That's great and all but does it really translate?
A new study just showed that a single psilocybin treatment decreased heavy alcohol use by 88% and ½ the participants had stopped drinking 6 months later.
What? Look…alcohol addiction has been a brutal slog of failed interventions forever now.
And cannabis??
The set-up:
The result:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987443/
SUD (including cannabis) is substance use disorder. John Hopkins is all over this research but expect more crazy results like this.
Look…there's no accounting for psil just balancing GABA or serotonin or the opioid system from one use.
This can only be epigenetic editing to our trauma code!
We looked at how to edit our mental health past code.
Psychedelics aren't legal…yet.
You can also look to medicinal mushrooms to have a more slower effect (CBD also causes "fear extinction"...a slower paced but powerful effect).
We have a medicinal mushrooms and mental health with effects across every pathway mentioned.
This is about long term repair and balance!
Check out the review. Exciting times…a complete jump in options.
Cannabis should be recreational…not self-medication. Tapering with supportive tools that fill the original gap for what cannabis was used to replace/support…until tolerance killed the party.
Be well. Take care of each other. Take care of yourself.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>A look at the issues that might not be mentioned in the 10 minute doctor appt
]]>Lots of new headlines lately around SSRIs.
Interesting this is popping up now when most of this has been well established for years…maybe decades.
Our founder was prescribed Lexapro after a 10 minute visit with GP and it led to a brutal experience culminating in an ER visit following 3 days of no sleep.
That whole story explained but estradiol and progesterone support was all that was needed during a brutal perimenopause.
Turns out estrogen drives serotonin and in goes into a tailspin late 40's.
Lexapro seems to be the go-to recommendation for women in this situation but the newest trend is even more concerning.
Young people are the new budding market for SSRI prescriptions. Look at teenagers and Prozac through 2006:
And it only gets worse from there...
We've already looked at how SSRIs really work and also reviewed their effectiveness date (small increase over placebo for very severe depression).
Let's look at what the doctor did NOT tell us about.
Understanding how SSRIs work is critical to making an informed decision. We're not even talking side effects but basic mechanisms.
These are the topics we'll cover:
We really need to introduce the star player.
Serotonin is a powerful manager in the brain and gut that literally guides ALL human behavior.
https://www.ncbi.nlm.nih.gov/books/NBK27940/
We have big reviews on serotonin but some quick notes:
Serotonin is just fascinating when you dive into the research. It's the manager of "self esteem" as much as any one player can guide such a complicated sense of self.
It's not the "feel good" transmitter. More like the "feel right in your own skin" player.
More on that below will become apparent.
From a biological point of view, it's there to inform you that your situation here and now is ideal for survival and thriving. Or isn't!
When you're sick, tryptophan (which serotonin is made from) gets depleted to starve out the virus/bacteria (which also uses it to build more of themselves).
Your mood goes down..a signal that you should rest. Not a good time to explore the world!
Serotonin is made from tryptophan but it's downstream metabolites are more interesting.
We mentioned BDNF, our brain's fertilizer above.
If there is a benefit for mental health, BDNF is the driver.
BDNF is actually part of the immune system which is a big clue to how you can actually address anxiety, depression, and just about every mental health issues.
The immune system is the future of mental health.
The newest studies on psilocybin (which will revolutionize mental health shortly) show that genes in the immune system are affected to cause its long term effects on depression and anxiety.
Read that back over. The immune system.
BDNF is on the repair side and when it's outgunned, anxiety and depression emerge.
The opponents?
Sound familiar?
Check out our trauma and mental health review to learn more.
So…with that in mind, what's the basis behind SSRIs since they're prescribed to millions of people including children at an increasing rate?
The general spiel is that SSRIs keep serotonin from being absorbed by the neuron thus allowing more of it to be available.
Essentially…more serotonin the brain!
The real star should be apparent from above. BDNF!
This is why SSRIs don't work for a few weeks and in fact, can make anxiety/depression symptoms worse!
BDNF is brain building and that takes time otherwise, the increase of serotonin would have a pretty immediate effect (like benzos do with GABA - see benzo review).
Goodness. Even more interesting, when CB1 (where endocannabinoids function) is blocked, this effects also goes away.
We're not surprised…see CBD and BDNF or the endocannabinoid system.
One more piece of information…critical to much below.
The way SSRIs actually perform this trick with serotonin is via…histamine!
In fact, SSRIs jack up histamine in the brain which has a knock on effect of increasing serotonin availability!
You'll see below how you can get serotonin syndrome (too much serotonin) just by blocking the breakdown of histamine.
This is really really important for a great deal of below.
Okay..we have a lay of the land. Let's get to the #1 enemy.
This is really the crux of the problem with SSRIs, SNRIs, and many medications really.
When you artifically boost or suppress a key pathway in the body or brain, it's not without consequence.
Remember…serotonin manages EVERY aspect of human behavior.
Every. Aspect.
How does the brain respond when an outside drug comes in and boosts serotonin levels?
It pushes back!
Longer term, the brain will actually decrease the number and sensitivity of serotonin receptors.
That's the whole basis for tolerance!
This means your baseline serotonin function is decreasing with time and it's why dosages have to go up and/or other medications have to be layered.
What happens when the SSRI goes away? Goodness.
You're in a much worse situation than when you started and keep in mind…doctors can't test your brain serotonin levels!
SSRIs actually work for about 30% of the people who try them and it's primarily major depression patients.
Placebo accounts for most of everyone else. This likely means that their serotonin levels were not the root of the issue (or you would see a better response).
Again, see the research on SSRIs here.
SNRIs have the same issue but with adrenaline (norepinephrine) added to the mix. Now we're bringing the autonomic (fight/flight versus rest/digest) nervous system to the tolerance party.
Coming off of lexapro was harder than coming off of Xanax.
Brutal. Brain zaps. Panic attacks. Insomnia. Gut issues. That's…tolerance.
Studies show that it takes about 30 days (at best) for serotonin receptors to come back on line (the DNA has to be turned on to make the receptor proteins) but many people are finding effects for months or years.
Some are seeing this system "shifted" down for much longer periods of time.
In fact, that's part of the current headline onslaught…sexual dysfunction for years and years.
Let's start to dig into what this is.
One of the major complaints around SSRIs is flat affect. Feeling…less about everything.
What's going on here?
Remember…when serotonin is in a good range (not under assault or being juiced up), we feel…pretty good!
Serotonin manages dopamine which is our reward circuit.
Sure, it's there to drive survival (food, sex, water, etc) but at smaller levels, it gets you out of bed, makes you study, and even keep yourself up!
It's side hustle is as your "ambition" driver.
So…what happens with longer term SSRI use (remember the slow chipping away due to tolerance)?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674976/
Escilatopram is lexapro, the go-to for women in perimenopause (40's).
Goodness…so dopamine loses its bite. Over time with SSRIs. Just a head's up...loss of dopamine is excrutiating...pure misery.
This speaks to the common complaint of "feeling flat".
Goodness….the whole reason SSRIs are prescribed is to address this very issue with depression. In fact… "low motivation" is a listed reason for precribing.
The research on anxiety is much less rigorous (see SSRI research).
Longer term, you're actually making things worse due to this tolerance effect.
Let's look at just one aspect of this dopamine watering-down effect longer term.
There's a new term bubbling up now. PSSD.
Post SSRI Sexual Dysfunction. Full review via that link.
It speaks to a long term dampening of sexual function, desire, and libido AFTER stopping SSRIs.
Years even.
We'll get to that but lets look at the effect while on SSRIs.
Remember, dopamine is a learning-directed player…this behavior resulted in better chances of survival, water, food…sex. Reward it. Lock it down in the brain. Go back to it!
Not really your survival. Your gene's survival. Nature is brutal…sorry.
Just some benchmarks…
Addiction is just tooling our dopamine system to learn a bevahior!
Now…with longer term SSRI use, we have desentization of both serotonin (feel "right") and dopamine (do that again).
Sex drive is going to suffer.
In fact…
Goodness..the whole sex complex. It's not just erections or orgasm or lubrication. It's all of it!
The lack of interest really speaks to the dopamine pathway. We did a deep dive on orgasm and CBD. Prolactin is no slouch though as well.
Serotonin governs the desire/preparation for sex while anandamide is critical to orgasm.
It's not that common though, right?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034069/
Now compare that with the 80% of new prescribed patients who don't know about this effect.
Mismatch much??
What's going on with the long term effect? Remember that serotonin receptors should come back on line after SSRI discontinuation.
The official literature is a few weeks…matching what we noted above on receptors.
However, people are reporting back effects that go on for years!
Let's go there now.
Serotonin is a powerful player in development. Keep in mind the brain doesn't really enter adulthood (remodeling from puberty ends) till around age 25.
Some systems continue changing well past that point (white matter tracts, etc).
That's the issue with THC use which can affect this architecture build in a negative way when young. see CBD to protect against THC.
So…what do we know about SSRIs and this whole buildout?
First, SSRIs do make it across the umbilical cord to the fetus.
This is literally a period of brain development explosion…especially the 3rd trimester.
What about breast milk?
https://www.uspharmacist.com/article/antidepressant-use-in-the-breastfeeding-patient
Why does this matter?
Animal studies show that when SSRIs are used during maternity, the gut nervous system is poorly developed.
Serotonin is even more prominent in our "2nd brain" - the enteric nervous system that manages our gut.
Most serotonin is actually made in the gut. Studies show that the serotonin receptors will literally internalize and make themselves less available with SSRIs.
Remember, serotonin drives BDNF which is the primary builder of nervous system. It's especially busy during development.
Think..
The latter goes through to age 25 in terms of brain development.
The net net…we might be building with a shaky foundation around serotonin and dopamine function.
Studies all tout how SSRIs boost BDNF initially but you don't see studies on long term use.
Afterall, BDNF is THE key switch with SSRIs or any supplement/activity that improves mental health.
We have a huge review on BDNF. In fact, newer research is showing that SSRIs can interact directly with BNDF:
https://www.sciencedaily.com/releases/2021/02/210218141716.htm
The key during development is that serotonin manages the buildout of its own system!
https://pubmed.ncbi.nlm.nih.gov/11750793/
So…follow the breadcrumbs:
If we have early SSRI use during brain development, we may be baking reduced function into the cake due to...tolerance!
That's very depressing. It's definitely not told to the countless teens and children being prescribed now.
A few notes.
Progesterone and it's powerful metabolite allopregnanolone is a huge player in depression both during and after pregnancy.
The new blockbuster drug for post partum depression (costs $25K) is a synthetic version of allopregnenolone.
Progesterone deficiency directly drives preemie risk and complications.
Get tested. Pregnenolone (cost $10- pregnenolone guide here) is a great way to support all steroidal hormones but work with your doctor.
Check out review on pregnenolone or post partum allopregnenolone.
As for teenagers, check out depression cheat sheet and guide.
Look…estrogen drives serotonin and it's in flux during puberty. We learned how powerful this is on the other side during perimenopause (when it's leaving). See estrogen and mental health.
Testosterone gets converted to estrogen in the male brain by aromatase to drive serotonin.
Progesterone drives GABA, our calming pathway. (key to anxiety).
All are in flux during this period and probably under duress from estrogenic chemicals, additives, and food in our environment.
Berberine has interesting results for hormone balancing. Check out the fats article (omega 3 versus 6 matters). Get tested.
It really requires a full article but the brain is being full remodelled (rational pre-frontal cortex is temporarily offline). What do you expect??
Rehabiliating serotonin function is a different matter and it requires tools that don't build tolerance (more on that later).
We didn't even cover the other downstream effects like acetylcholine (more below).
Let's turn to an interesting piece no one is talking about.
We know that SSRIs temporarily boost serotonin availabililty till tolerance kicks in.
We also know that BDNF is a key downstream player in the end-results. This is true for all things that boost BDNF.
Here's the fascinating piece.
The mechanism by which SSRIs (the chemical) does this may rely heavily on another powerful brain player…histamine.
So…let's tease this out.
We'll translate this:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648163/
So…Celexa increased histamine in a specific brain area when serotonin pathways were blocked, the histamine boost disappeared.
They're intimately linked.
To put it simply..
https://pubmed.ncbi.nlm.nih.gov/25820671/
Now it's nuanced. If histamine spikes due to infection, the benefits of SSRIs go away.
We've been saying…the immune system is the future of mental health. Check out neuroinflammation guide.
The histamine piece is interesting in terms of the side effect profile:
Check out the massive guide for histamine.
One note…you can cause serotonin syndrome (too much serotonin) just by taking drugs that block removal of histamine!
Let's turn to insomnia, one aspect at play with SSRI use.
Serotonin is a master regulator of all things sleep. It literally gets turned into melatonin.
So…why is insomnia listed on the side-effect profile front and center?
First, we have the tolerance piece where our natural serotonin is slowly being whittled down.
The histamine piece is more interesting.
Histamine directly governs the sleep wake cycle with GABA. Histamine is excitatory in the brain separately from its immune function.
Again, check our histamine and insomnia review.
Need an example?
Okay…anti-histamines.
The go-to for millions of women who are losing their progesterone (and their GABA) in their 40's. Benadryl and Tylenol PM.
Too bad they rip acetylcholine, a key driver of dementia risk.
Drowsy is the first side-effect.
Can you take anti-histamines and SSRIs?
They interact! It can be strong so it's not advised and now you know why.
I
n fact, one anti-histamine is regarded almost as an antidote for serotonin syndrome:
https://www.singlecare.com/conditions/serotonin-syndrome-treatment-and-medications
Check out our review on serotonin syndrome.
The net net of SSRIs and sleep is pretty clear:
https://www.sciencedirect.com/topics/neuroscience/selective-serotonin-reuptake-inhibitor
That's a laundry list of bad effects which doesn't match serotonin as a general sleep manager!
One note…lack of sleep looks just like extreme anxiety in MRI scans of the brain!
Prozac has a huge red flag here longer term..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866255/
Serotonin is just too powerful a pathway to monkey with! Check out our big review on sleep.
Let's turn to another issue not discussed much.
There can be a risk of homicidal or suicidal tendencies with SSRI use and specifically for younger men with OCD.
It's not relegated to this group but they appear to be more at risk.
We did a huge review on this whole topic here.
Essentially, too much serotonin (remember…they can't test your brain levels) can create an extreme form of agitation in the brain called dyskinesia.
You literally feel like you're coming out of your skin. It's an extremely punishing condition and form of existence.
The risk goes up for adolescents and especially for males…and even more for males with OCD.
Check out the deep dive with lots of studies on violence, aggression, and other factors with SSRI use.
Especially when younger.
Let's turn to our autonomic nervous system.
We have an entire background system running that we're not consciously in control of.
It's comprised of two sections:
They generally oppose each other.
The rest and digest system is driven by acetylcholine, the "calm and focused" player.
The fight or flight is driven by norepinephrine (adrenaline).
You probably know how the latter feels.
SSRIs and definitely SNRIs directly affect this nervous system.
Even just SSRIs have a negative effect on acetylcholine:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068400/
Goodness…SSRIs rip acetylcholine longer term.
This is not good for dementia risk, ADHD, and just good brain function.
As for dementia (directly tied to acetylcholine deficiency):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079596/
75% increase in risk! Tricyclics were even worse at over double the risk.
ADHD should be front in center if we're hitting the acetylcholine pathway.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450015/
2 and a quarter times the risk. For the baby. Choline is a huge supplement during pregnancy anyway (eat your eggs!!).
The seat of acetycholine function is the vagus nerve, a key hub between the gut and brain.
In fact, newer research is showing that SSRIs don't function without it!
https://www.researchgate.net/publication/336239022
The gut's a huge player with serotonin!
Check out review on how to support the vagus nerve without tolerance.
Let's turn to the worse effect. One we know intimately (unfortunately).
Serotonin syndrome is basically too much serotonin.
It's actually very dangerous and you should seek emergency care if you suspect this is an issue.
The more common symptoms are:
https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758
How common is it?
That's not nothing (apologies to high school english teachers).
Especially with millions of subscriptions out there.
Again, this is very serious so get emergency care right away.
Our founder experienced it (story is here) and it was worst few days of her life.
We did a deep dive on serotonin syndrome but a few interesting notes.
It can occur weeks AFTER discontinuing SSRIs (more on this below)
The primary driver?? A histamine explosion!
In fact, you can cause serotonin syndrome (wait for it)...by blocking the removal of histamine!
https://www.dshs.texas.gov/IDCU/disease/tb/forms/PDFS/SerotoninSyndrome.pdf
Anti-histamines are now key tools against serotonin syndrome and it speaks to the powerful interaction between SSRIs and histamine.
You see insomnia front and center in the symptom list. Our founder couldn't sleep for 3 nights before the ER crash.
Histamine is excitatory in the nervous system so the other symptoms all fall in line..
Restlessness, agitation, dilated pupils, quickened heart rate.
The standard treatment is benzos, unfortunately (see benzo review).
That's trading one bad apple for a rotten bunch (addiction and tolerance builds very fast).
But get this...
https://www.aafp.org/pubs/afp/issues/2010/0501/p1139.html
What's cyproheptadine you ask?
https://www.webmd.com/drugs/2/drug-8879/cyproheptadine-oral/details
Goodness.
Here's our histamine toolkit and we have a huge histamine guide.
What about the long term serotonin imbalance?
What about the poor people who see their serotonin function debilitated years after SSRIs?
This is becoming common with younger people and PSSD (post SSRI sexual dysfunction).
Technically, serotonin receptors should come back online about 30 days after discontinuation.
The DNA needs to be turned back on to make the receptor proteins and this takes time.
This is all brand new so we don't have hard studies on this but we can view it from two lenses.
For the first piece, do no (more) damage.
Serotonin is a buffer for the following:
These will literally draw down serotonin so we have to address them first and the best way is to balance the immune system where "markups" reside from past trauma.
We have a huge review on editing your health's past and how the immune system is the future of mental health.
Past trauma will downregulate serotonin, GABA, BDNF, and more. It will upregulate inflammation, cortisol (stress hormone), and glutamate.
Our steroidal hormones are front and center here.
Estrogen and testosterone (via aromatase conversion to estrogen in the brain for males) is a key driver of serotonin.
Test your hormones and support them as needed with bioidentical hormones. Big reviews on testosterone and estrogen for mental health.
Here's an example with CBD (our focus of research) on serotonin to show how the exhaustion piece works:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Let's translate because this is too fascinating.
Injury was applied to animals which exhausted serotonin levels (governs our pain thresholds).
As a result, anxiety, system-wide pain (allodynia), and serotonin (5HT) exhaustion occurred.
CBD reversed these effects and "rescues" serotonin function!
That's the word we want to see! Rescue. Normalize. Modulate.
Not boost like SSRIs. This way, we don't see tolerance and push back.
Here's our serotonin rescue toolkit with that in mind:
Then, the second part…repairing and rebuilding.
This is tougher but more important.
BDNF is our brain's fertilizer. It's the heavy lifter and we need to support it directly.
That's why exercise and mindful meditation are so beneficial (see more here).
Psilocybin (from magic mushrooms) is an explosion in brain repair while CBD isolate works gradually but constantly.
Medicinal mushrooms are also interesting options to rebalance our immune system and boost this repair mechanism.
Basic nutrients figure in strongly for DNA methylation including:
Avoid seed oils (heavy in omega 6) and processed food generally.
So…the best course for serotonin rescue…
As we see new research (and there will be with the 1000's of new long-term serotonin sufferers), we'll add it here.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
Tips and Research around how CBD works for flight anxiety versus benzos
]]>We received an email the other day with a simple question..
"UK banned benzo prescriptions for flights…can I use CBD instead?"
Yes!
The type and dose of CBD though is very important as we'll see below.
In fact, we'll go through an entire CBD protocol for flight anxiety.
We'll use research such as the powerful public speaking study for people with diagnosed social anxiety (which sounds like torture to us) as our basis since it's the closest equivalent.
After all, 40% of the population has some fear of flying and up to 5% have crippling fear.
Generally, flying these days is stressful for everyone and we'll see how CBD is a powerful stress response buffer while also looking at other tools.
Here's the flight plan:
Let's get started! Takeoff is at 9 am.
We have a massive review of CBD and phobias which neatly captures what's going on with any intense fear.
We'll focus on three key players plus a "network" in the brain:
The circuit actually matters here.
We have an older area of the brain called the amygdala which is tasked with threat detection among other things (emotions and impulses being relevant).
Keeping this area in check is the prefrontal cortex (newest addition to the human brain).
When the amygdala fires too strongly, we can have intense fear or phobias…such as fear of flying.
This sets off a cascade of chemistry in the brain starting with the whole cortisol pathway.
Cortisol is our primary stress hormone.
With enough time or amount of it, we start to overwhelm the opposing forces.
First, there's GABA, our brain's brake pedal…which just happens to be the target of benzos!
Benzos build tolerance and are incredibly addictive which is why the UK no longer allows prescribing for fear of flying.
It's just not worth it as they quickly become the new opioid crisis.
Xanax and Ativan have street names and values now.
Once GABA gives way, serotonin does the heavy lifting for stress response among its many tasks (manages ALL human behavior).
Pain, stress, infection, trauma, etc can all exhaust serotonin. That's why you feel low when sick or hurt.
Serotonin is the target of SSRIs but they build tolerance and are not used "as needed" this way. It's tricky messing with serotonin since it's so integral to every brain system.
Our backup stress response system is anandamide, the so-called "bliss molecule".
THC mimics anandamide which is how it works but it hits the receptors too hard and for too long so you can have rebound anxiety and tolerance longer term.
There are also big histamine issues there for roughly 33% of the population which feels like…anxiety!
Histamine is excitatory (eats up GABA above).
That's the tug-of-war going on in the brain. Why flying? Why not!
The brain is complicated and early interactions, etc can establish certain behaviors as triggers for this whole anxiety cascade.
Longer term, you can work to dislodge this fear but for now, we need to make the flight!
So…where does CBD fit into this process.
Where THC boosts activity similar to anandamide, CBD supports it…when LOW!
Like a feedback mechanism.
That's why you don't see overdoses, side effects like THC, or effects on cognition/sedation.
You see the effects of CBD on the entire cascade above when stress becomes excessive.
Let's wall through it:
Let's get started!
Double-blind, placebo 2021 study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
SO…about the same at meds. Hello benzos and SSRIs!
The summary…
"acute stress anxiety"...i.e. stress caused by a specific stressful situation. Ummm...flying maybe!!
Check out CBD and stress response for lots of studies and detail.
A great deal of this comes down to the first barrier against stress.
GABA is the "right now" face of calming fear and anxiety.
CBD has a direct supporting effect on GABA when low. Technically, it's called an allosteric positive modulator.
Essentially, it supports GABA function when low (such as being exhausted by cortisol and stress and take off).
This speaks to its calming effects on seizures, anxiety, sleep, and more.
What we don't see is the one-direction push of GABA like with benzos, alcohol, THC, and more.
That's the trajectory with ever-increasing GABA levels:
Boosting GABA in one direction follows the same trajectory and we don't see this with even high levels of CBD which is critical when you need to function at an airport!
More research on CBD and GABA versus benzos and alcohol.
Let's turn to the long term player.
This is a major player in the long-term manifestation of flight anxiety.
In fact, phobias are now partially understood as an inability to regulate serotonin (it's either too high or too low).
Serotonin is a stress response buffer (second line after GABA).
CBD also supports serotonin when low.
Here's our favorite example of CBD's effects.
An injury causes pain, anxiety, and dysregulated serotonin function. CBD's effects:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Let's translate that…it's too important.
After the injury (remember…pain exhausts serotonin just like fear):
Not boost. Not increase. Rescue! You see this all over the research with words like normalize and modulate.
THC pushes in one direction so you get a rebound effect (the other way).
CBD doesn't build tolerance or have withdrawals!
Remember…too much serotonin is just as troubling as too little (maybe more so…see serotonin syndrome).
Huge review on CBD and serotonin.
Next…the backup.
This is one of our primary endocannabinoids…the system that CBD works in!
It's made on demand and quickly broken down. It's a big wet blanket in the brain on anything excessive (stress, inflammation, etc).
THC jacks up levels of activity similar to anandamide but as a result, it can have side effects, rebound, and even cause anxiety!
CBD supports anandamide when low by blocking FAAH, the pathway that breaks down anandamide.
We don't see the "high" with CBD which speaks to its feedback effect.
A big review on CBD and endocannabinoids including anandamide can be found here.
That's all great for the upcoming flight at 9am…but can we can adjust our long term trajectory for flight anxiety?
This is fascinating! You can actually unwind the marbelized fear response in the brain!
They can actually see it on brain scans:
https://www.neurologylive.com/view/phobias-and-brain-activity
There's that amygdala/pre-frontal cortex overwhelming effect (too much primitive fear response).
Here's the exciting part. CBD supports the system that FORGETS fears.
Especially important for PTSD and trauma but let's walk through this:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121237/
So…
Goodness. We can drop the mic now.
A great deal of this comes from effects on BDNF, our brain's growth/repair pathway.
Learn all about CBD and past trauma here.
You don't have to have phobias…it's not locked in stone (just locked in brain pathways that can be erased).
Let's jump to our best proxy for fear of flying.
This is a great example of CBD for episodic and intense anxiety.
They took people with a diagnosed social anxiety disorder and subjected them to a public speaking test.
Goodness..just poke me in the eye with a sharp stick (I have irrational fears around my eyes!!)
The results:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/
There's a test called N-SSP…essentially a questionnaire of how you see yourself in terms of positive or negative.
The results:
So…pretreatment with CBD made people with social anxiety "feel" like the control group without social anxiety!
Public speaking requires a lot of mental functions…speech, thinking, etc.
CBD did not adversely affect any of that!
Translation…you'll be able to get through customs without them thinking you're a terrorist or "on something".
Big review on CBD and public speaking study or CBD and performance anxiety.
That study is great because it really points to how much CBD and when to take it.
Let's go there!
This is where many people go wrong with CBD. They're way undershooting levels of CBD according to research.
25mg is not going to do it!
The study above gave the participants 600mg 1½ hours before the speech test.
Also, they used CBD isolate (more on that below…super important).
So…our CBD and flying protocol:
That's it! You may find that 300mg does it for you since we're all different but 600mg is the gold standard based on multiple studies for "acute" (right now, really bad) situations.
Let's talk about the kind of CBD.
First, the CBD needs to be from an FDA-registered farms in the USA.
The following is mandatory:
Testing is available at top of any page.
Next is the type of CBD.
CBD isolate matches the research but most importantly, it takes into account…histamine.
Histamine (source of allergic reaction) is excitatory in the brain. It eats up GABA and drives a fight or flight response since it's tasked with getting bad things out of the body.
That's the exact opposite direction we want to go before getting on a flight.
CBD itself calms histamine but full spectrum materials can actually trigger histamine and even anxiety itself! As does THC for rough 33% of the population!
40-60% of the population has histamine issues and this number goes up as we get older and for women (when progesterone leaves the scene).
99% of the research is on CBD isolate while 99% of the marketing is for full spectrum.
Then there's cost and levels.
Each dropper is 200mg so 3 droppers would hit the 600 level right away.
Again, with the under-tongue trick, you may find fewer works as well.
Longer term, 300mg daily is the key to the "fear extinction" piece since that's peak neurogenesis (brain repair/rewrite).
Let us know of any questions and safe flights! Much calmer flights.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
Understanding progesterone's role in the immune system may be THE key to mast cell and histamine response.
]]>We learned the hard way…over 2-3 years.
The full story is here but perimenopause sent the founder reeling and so much suffering could have been avoided with one simple fix.
Supporting progesterone!
We'll look at the how's and why's below but for any woman over 40, progesterone is the first place to look if you suddenly can't eat certain foods or use certain cosmetics.
The interaction of estrogen and progesterone directly affects this question and we'll look at their very different trajectories over life.
We have a massive review of progesterone for immune, sleep, and mental health but our focus here is on histamine and mast cell activation.
These are the topics we'll cover:
Let's get started. This question keeps affecting younger and younger women and you'll see why below.
For people with MCAS, this may be old hat but let's give a quick recap so that the rest of this review makes more sense.
First, it's important to understand that the entire histamine pathway sits squarely within the immune system.
Mast cells (named for their engorged look from a german root word) are the armory for histamine and a range of different inflammatory agents.
They are really the forward guard…early warning system.
If they detect foreign entities (bacteria, viruses, chemicals, etc), they release histamine which is tasked with getting the interloper OUT of the body FAST!
Hence, the common allergic reactions:
We have a massive histamine guide (really interesting what it does in the brain and gut) but within our immune context, it's all about responding to disturbances from outsiders.
Beat cops.
Early infection, trauma, and stress can hyperactivate our immune system and that includes mast cells/histamine but the real power players are…steroidal hormones. Learn about that here.
Let's go there.
Every cell in your body and brain has receptors for progesterone and estrogen.
EVERY Cell!
Think about that. This is not just about reproduction.
Generally speaking, estrogen boost immune response (mast cells more active) and progesterone calms the immune system (mast cells less active).
Don't trust us...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603032/
And…
https://pubmed.ncbi.nlm.nih.gov/17166400/
The question…is why?
This gets interesting.
It comes down to the amniotic sac!
Mother Nature generally likes to multi-task existing pathways in the body. That's why medications can have weird side effects and knock-on effects.
The amniotic sac is actually made from the father's DNA…it's a hostile takeover! Nature's not always pretty.
The immune system sees this foreign entity and tries to attack it. Progesterone is the buffer there and it basically suppresses mast cell and histamine response during pregnancy.
Progesterone spikes during pregnancy and turns off the early detection system.
You see a range of weird responses that result:
In fact, low progesterone is now regarded as a primary driver of premature births (the immune system is winning).
https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/ijgo.13187
So…what's the problem with progesterone keeping estrogen balanced in our mast cell activity level?
I'm sure your OBGyn explained this to you in your 30's. Not!
We have a huge review of why 25% of women get hit with debilitating (yes..that's the word they use in NIH study) perimenopause.
We just weren't designed to live past roughly 35 (our deep deep ancestors rarely did).
It starts this deep dive early 20s and continues down beyond 40 and continues to almost nothing.
Estrogen, however, remains pretty stable until the late '40s (for most women) then goes through a roller coaster ride spasm (perimenopause) which can feel just brutal.
Keep in mind that estrogen drives serotonin (our master mood and stress manager)...all human behavior really.
Progesterone drives GABA, our nervous system's brake pedal, and key to sleep, anxiety, and more.
The mismatch is that progesterone drops much more quickly than estrogen which is a big problem across almost every pathway but especially histamine and mast cell activity.
You start to see the telltale signs of mismatch during our 40s.
Check out the progesterone guide or our estrogen and mental health guide.
Just an example with MCAS…DAO, the enzyme that breaks down histamine in gut is all the rage for MCAS activation.
Okay…
https://www.larabriden.com/the-curious-link-between-estrogen-and-histamine-intolerance/
Love her stuff by the way!
This is if everything goes well…but there's more to the story these days!
There is another wrinkle to the whole story.
Naturally, progesterone is fleeing the scene long before estrogen. This leads to a lot of talk around "estrogen dominance".
Really, it's progesterone inferiority!
That's in a world without plastics, pesticides, hormone disruptors and more in our food, skincare, and everywhere!
We have many sources of extra estrogen that we're swimming in daily.
Just a few examples..
Phytoestrogen in food - essentially plant-based sources of estrogen (such as soy)
Hormone treatment in animal sources of food:
https://pubmed.ncbi.nlm.nih.gov/22172713/
Great so that's both plant and animal sources if not organic.
Then there's plastic. Yes, that Starbucks cup!
That's BPA and but same holds true for lot of chemicals.
But it doesn't stop there.
What about PFOA, the forever chemical that we all have now in our bloodstream and it's even showing up in cord blood for newborns?
Oops...
https://www.sciencedirect.com/science/article/pii/S016041201932759X
Goodness…estrogen dominance indeed.
This might speak to why 20 year males today show average testosterone levels at half the level from just 20 years ago!
See our testosterone review to see why this isn't just about libido and muscles.
Then, there's the crazy move to linoleic acid (seed oils) as our primary fat source since the '70s (directly tracks obesity, diabetes, and testosterone drops).
Go figure..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846030/
Ladies (and men)...you've been swimming in estrogen while progesterone was already on the way out naturally.
That's why MCAS and most immune diseases affect women at an 8:1 clip compared to men.
So…how do we buffer this onslaught (and it is that).
Before we started progesterone, we couldn't eat half of the menu, were popping DAO like it was candy, and avoided all cosmetics/sunblock, etc.
That has completely gone away and eating peppers is no issue now! Spicier the better (which matches longevity studies on capsaicin).
A few notes.
First, get tested. The Dutch Test is the best to determine how your body is actually metabolizing hormones.
Bioidentical is a must and if your doctor doesn't know the difference between synthetics (progestins) and the real stuff, you may need a new doctor.
One (of many) pathway examples:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960754/
Remember that cancer and blood clots drove the fear train that a 2001 study caused which drove millions of women to drop HRT.
Progesterone (bioidentical)...33% reduction in cancer risk in combination with estrogen.
We also looked at oral safety at the Bijuva review.
Prometrium is a prescription option for bioidentical progesterone. Estrace is the equivalent for estradiol.
Remember, they oppose each other in many pathways and balance is the key.
The Dutch Test helps you dial this in since everybody is different. For example, some women breakdown their own steroids quicker or slower depending on COMT genes.
Just don't trust the…"Your numbers are fine for your age" if you're not feeling well.
The histamine response is a canary in the coal mine! This a great signal that progesterone is outgunned.
Test and adjust with bioidentical.
The founder takes progesterone at night (incredible for sleep) and estradiol (Estrace) in the morning.
This matches our natural cycle as progesterone drives GABA, the key to sleep, and estradiol is generally pro-growth/repair and stimulating.
Vitamin D is a steroid as well and it manages the function of both estradiol and progesterone.
Endocrinologists are aiming for 60ish ng/ml. Get tested and support as needed.
We have a huge Vitamin D guide.
We created a Top 10 Tips guide for mast cell support but the quick takeaways.
We have deep dives on all of these but a quick recap.
The prerequisites:
Okay…that leaves a few options. Here they are.
The highlights…
Mag is a powerful wet blanket on stress and inflammation.
When mag goes down, mast cell activity goes up!
https://pubmed.ncbi.nlm.nih.gov/24477254/
Mag is also a key rate limiting factor for DAO (which breaks down histamine in the gut).
Glycinate gets across the blood brain barrier best.
We take 3 x 100mg daily for stress response and migraines. More on magnesium glycinate.
We have a whole review on CBD and histamine or CBD and MCAS but the quick takeaway.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433789/
Basically, CBD triggers a key anti-inflammatory pathway (PPAR) which boosts the pathways that "resolve" or calm mast cell activation.
MDSCs are the "off" switch for mast cell activation.
And PPAR?
https://pubmed.ncbi.nlm.nih.gov/35636075/
This is the switch you want to throw when mast cells are running amok and CBD isolate has the finger on its trigger.
One note…the kind of CBD is critical. Full or broad spectrum CBD can actually trigger mast cell activation as we found out the hard way when we started this journey.
We already went through the powers of progesterone. We have a whole review on why progesterone is so critical to histamine response.
Get tested!
Support with bioidentical as needed.
Prometrium is an RX option for bioidentical support. Progesterone works hand-in-hand with estradiol which depends on where you are (pre, perimenopause, menopause).
Either way, progesterone starts dropping much earlier (50% by age 40) than estradiol and hence…the mast cell issues!
Mast cell activation is the canary in the coal mine, so it's important to catch this early.
Every cell has estradiol and progesterone receptors.
For men, testosterone is equally important (and dropping). It's more immunomodulatory which means its effects are more nuanced. Still important to test and support.
Big guides:
Speaking of steroids.
Vitamin D directly manages the immune system response including mast cells.
Let's put a point to it:
https://covid19-evidence.paho.org/handle/20.500.12663/1569
Get tested and aim for 50-70 ng/ml. We have a whole review on Vitamin D but like steroidal hormones, mast cell activation is just the tip of the iceberg for effects with 1000's of processes dependent on D including vital DNA repair processes.
Let's now turn to tuning up the immune system.
Mushrooms are powerful players to dial in our immune response.
Certain species can literally reset our immune "setting" from TH1 to TH2…from hypervigilant to balanced.
For example…Chaga species:
https://pubmed.ncbi.nlm.nih.gov/29175507/
Let's translate the Klingon.
Basically, chemicals in the chaga mushroom not only calmed mast cell activity but suppressed the hyperactivation of the entire immune setting in the gut.
Remember, the gut sets the inflammatory state for the body and brain since it's the site of first contact with most bad actors (bacteria, fungi, etc in GI tract).
That's just one example…of many!
Review of medicinal mushrooms.
Next up…another endocannabinoid.
Where CBD acts as a feedback support when our endocannabinoid system is exhausted, PEA is a naturally occurring backup player.
It supports anandamide (our primary inflammation calming agent) when it's outgunned!
The net results:
https://pubmed.ncbi.nlm.nih.gov/23813098/
Goodness. In this example in the brain…
You can see similar effects across the body (skin, gut, etc).
More at our PEA guide.
Goes to show you how important the endocannabinoid system is for balance.
Okay…that's our toolkit for histamine. Deep dives on each of those.
This glimpse into perimenopause is just the beginning. 'Dre's Story' offers our complete, research-rich journey into hormones, tools to feel better, and safety. The full Perimenopause Toolkit with new additions can be found Here. Please review so other can learn. Feeling better starts with understanding what is happening.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
A focus on the immune system and supporting traditional treatment for success
]]>You got the bad news.
Everything is getting set up for various forms of treatment such as chemo, radiation, and/or the newer forms of immunotherapy (very exciting by the way..you'll see why below).
After all, the immune system is specifically tasked with detecting and killing faulty cells in our body.
Are there options out there that can turn the tide in your favor without interfering with treatment?
That last piece is critical since many tools that have anti-cancer effects preventatively reduce oxidative stress and that goes directly against the intent of radiation/chemo.
We'll explain below but to answer the question…Yes! There are tools. Some are supplements and others are behaviors.
This is an exploration of stacking the deck as much as possible based on real research.
Here are the topics we'll cover:
Let's get started. You're going to love this research! We've seen it firsthand with friends and family in the middle of treatment.
Work with your doctor of course. Our friends have vetted the mushrooms and CBD isolate with expert doctors at UCSF and UCLA but double-check always.
Let's get started!
We first need to understand how the body gets rid of cancer.
It's all the immune system. The immune system is in charge of cellular birth and death cycles (happening all the time).
In fact, when a pre-cancerous or even virally infected cell displays signals of dysfunction, it's the immune system that detects this and then initiated cell death.
It's happening all the time....when the system's working correctly (more on that with Vitamin D and our steroidal hormones below).
The immune's weapon of choice??
Oxidative stress. When a cell is targeted for removal, the immune jacks up oxidative stress…essentially organic scissors made out of oxygen that shreds anything in its path.
Chemo and radiation are massive deliveries of oxidative stress…to both cancerous and healthy cells (which is why it feels so bad).
We have a whole review on oxidative stress but it's important to understand the primary weapon (of many in the body) against cancer so that we don't work against treatment.
That's Rule #1!
We also don't want the usual suspects:
Let's get to it!
We'll start from the most promising and work our way down.
If you've seen Fantastic Fungi on Netflix, you might be familiar with Stamet's introduction from his mom (and her stage 4 cancer).
Mushrooms generally have powerful effects on the immune system and certain species are showing impressive results with cancer specifically.
We have a massive review of turkey tail and cancer but here are some quick takeaways.
Let's look at just one substance in Turkey Tail called PSK:
https://pubmed.ncbi.nlm.nih.gov/12168863/
Okay…so randomized, clinical trials.
"Adjuvant" just means used along with traditional treatment.
In Japan, PSK or turkey tail is part of standard treatment within their health system.
It's been used for roughly 2000 years (recorded) in China and Japan.
Again, check out the full Turkey Tail review.
After enquiring directly with Stamet's group, they noted that 6 capsules of this Turkey Tail was part of the original protocol for his mother.
One note…turkey tail can slow serotonin function so we want to support that for mood, sleep, pain, etc.
Speaking of which…
The turkey tail review above actually splits duties with CBD isolate.
Like turkey tail, CBD's effects are varied and have a strong immune system effect:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869992/
First, understand that CBD is not THC or cannabis.
In fact, CBD directly opposes much of the excess of THC which speaks to the original meaning of the term "entourage effect".
It's not about "pot". CBD works like a feedback mechanism for our endocannabinoid system which is tasked with balancing other key systems including…
The immune system!
As a result, research is showing the positive effects of CBD across a wide…wide array of pathways:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869992/
Goodness.
So…
Just as important, there's lots of research on CBD and the symptoms of treatment.
CBD supports when low (feedback) the following systems:
It doesn't affect appetite but we'll cover that below.
The best part..CBD is showing tri-phasic responses:
We're not sure of another substance that can do this but it speaks to supporting the immune system which should do it naturally.
We use this one and 300mg/daily is peak neurogenesis (repair in the brain). 600mg is used for more severe issues.
Holding under the tongue for up to 60 seconds can boost bioavailability and after meals allows more to get past the liver.
Reach out with any questions. Ask your doctor but CBD isolate (just CBD) does not impact the oxidative stress delivery of chemo/radiation…to cancer or faulty cells!
Back to the world of fungi.
Turkey Tail is not the only mushroom species with anti-cancer effects.
In fact, when you dig deep into the mushroom world, they all have different effects and it's primarily through…the immune system!
There's a pretty good review here:
https://www.cancer.gov/about-cancer/treatment/cam/patient/mushrooms-pdq
A large scale review of many studies around cancer found the following:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794004/
The immune system can quickly get very complicated so let's take one example.
Reishi mushroom:
https://pubmed.ncbi.nlm.nih.gov/29607690/
Okay…so the polysaccharides (like PSK) in Reishi can increase the anti-cancer effects of immunotherapy.
In prostate cancer:
https://pubmed.ncbi.nlm.nih.gov/30272272/
Apoptosis is cell suicide initiated by our immune system (remember the oxidative stress assassin from above??)
There's a great look at different species here:
https://pubmed.ncbi.nlm.nih.gov/26770080/
Their summary:
Great…we're catching up with Japan and China where this is commonplace.
So…how do you get ahold of all these species?
We use this blend here from the same company (tied to Stamets).
Next up…the steroid we get from the sun (or at least our ancestors did).
D is a master regulator of the immune system (see a pattern here??).
Many people are deficient and that's based on the ridiculous RDA levels of 30 ng/ml. Endocrinologists want us closer to 60-70.
Again…immune system detects and destroys cancer. Hence the cancer risk creeps up as we get older mirroring the immune system aging.
D's a big part of that with over 1000 bodily transactions dependent including many DNA repair pathways (critical for cancer initiation).
There's the prevention side:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773074
Or…the relationship between D deficiency and cancer risk:
This information is provided by Breastcancer.org.
Or after cancer such as colorectal cancer;
Their definition of "high-dose" was 4000IU daily. So behind the times.
Get your levels tested. I have to take 10K daily just to get my levels to 60 ng/ml. I have a version of the VDR gene where I don't convert D well even with daily mid-day sun.
That's not very common though, right?
https://pubmed.ncbi.nlm.nih.gov/21310306/
And that's based on being under 20 ng/ml!! Goodness. The biggest epidemic you'll find and the cheapest to correct.
I'm sure your doctor has run the cheap (around $40) Vitamin D test many times…right?
Right???
Get tested. Supplement as needed. D also coordinates your steroidal hormones and both estrogen and testosterone support and manages…immune function!
As for breast cancer, notice that Vitamin D was beneficial there.
Big review on Vitamin D.
Next up…not just for sleep.
You're thinking…melatonin? That's just for sleep, right?
No melatonin (derived from serotonin) is showing many different facets now for neuroprotection and even cancer!
A lot is going on with melatonin but a key piece is that it blocks linoleic acid processing but really hits a host of targets:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503661/
To translate…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503661/
Meaning…to be used along with treatment!
As usual, we come back to the immune system and melatonin is immunomodulatory…it balances the immune response.
From this, we would expect the immune system to do its job better which is to target and kill faulty cells.
Hello…
https://www.explorationpub.com/Journals/em/Article/100178
The research (across many different cancers) runs from 20-50mg daily so it's a high dose. Ask your doctor of course!
Next up, is a general all-purpose immune manager.
Like with CBD isolate, we love when a supplement can show two different effects depending on the state of the system.
Turmeric (curcumin) is regarded as a general all-purpose anti-inflammatory.
However, that's not the whole story and we definitely don't want to ramp down the immune system (inflammation) when fighting cancer.
After all, the ability of your body to "see" cancer and attack it resides solely in the immune system.
An enemy from within!
As expected…the results should be varied and many:
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07256-8
Cancer likes to block the cell-suicide machinery and curcumin restores this process
It also activates pathways that directly impede and suppress cancer.
But…as an anti-inflammatory, can we take it with chemo/radiation since they primarily work by increasing inflammation (which kills cells indiscriminately)?
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07256-8
See why we like supplements that have different responses depending on the state of the system?!?!
Just like CBD isolate. Selectivity.
Studies look at 2000mg daily as a baseline but work with your doctor.
More info here:
https://www.cancer.gov/about-cancer/treatment/cam/hp/curcumin-pdq
Let's go south…to the gut!
We have a massive review on berberine.
It's interesting due to its effects on AMPK (more here), a powerful and primordial nutrient sensing pathway that changes the body from growth to cellular housekeeping. Huge player for longevity.
Metformin also hits this same pathway and berberine is a natural analog for met.
Since AMPK is such a basic pathway for all multi-cellular life, you would expect to see many different effects from berberine:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996556/
Many types of cancers. Many mechanisms. AMPK (and mTOR, its downstream cohort) is a big deal.
Immunotherapy is a huge advance now in the fight against many cancers. Go figure.
Berberine is interesting there..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996556/
The immune system…yet again. Also, it helped with neuropathy!
And berberine and turmeric together??
https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/
To beat the dead horse (terrible saying)...
"Immunomodulator" music to our ears. Not boost or suppress. Balance!
Research is reflecting 1500-2000mg daily for periods of time. Obviously, run everything by your doctor!
Let's turn to some interesting tools outside of supplements.
Glucose is the enemy in fighting cancer.
Cancer cells are unique in that they rely heavily on glucose to generate energy for their rapacious growth.
That doesn't mean that sugar causes cancer…research doesn't back that up. It's definitely not your friend.
The whole Warburg effect:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/
On the flip side, what about diets like keto which are primarily protein and good fats (see what that means here).
Carbohydrates are just sugar in a different form factor.
So…where are we with this?
https://pubmed.ncbi.nlm.nih.gov/31399389/
Essentially, keto or low/no carb diets mimic a form of fasting. Cue the AMPK pathway above!
This forces the body into housekeeping mode and a big part of that process is increased removal of faulty cells (called autophagy). Sound familiar?
Most importantly, we can use it with chemo, radiation, and immunotherapy!
Basically…the transition starves out cancer cells while our body switches to other pathways for energy (ketones and fats).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056920/
So…cancer is weakened in the face of standard treatment!
Along those same lines (AMPK), let's look at cold exposure.
AMPK is triggered by famine, drought, heat exposure, and…cold exposure!
Basically, times are bad out there, let's hunker down our cellular machinery.
Interesting new research on cold exposure and cancer specifically…
Piggy-backing off of the keto/AMPK angle, scientists exposed mice to cold temperatures with the following results:
https://www.newscientist.com/article/2332095-cold-exposure-stops-tumour-growth-in-mice-by-hijacking-glucose-stores/
What's interesting is that when the second batch of mice were exposed to cold but fed high-glucose diets, the benefits went away.
Essentially, cold exposure ramps up brown fat activity which uses up glucose stores to make heat.
Glucose. See our big review on the issue with glucose.
Again, it comes down to AMPK, a system-wide pathway for all things energy related.
As the researcher put it:
What about the opposite…when you can't eat due to chemo/radiation. Dangerous weight loss.
Even though our research focus is on CBD, we're not big THC fans. It builds tolerance and hits anandamide receptors (called CB1) too hard and for too long.
Longer term, this is the wrong direction for health.
That being said, CBD does not affect appetite and THC most definitely does. If a person has no appetite from cancer treatment, THC definitely boosts appetite.
"Wasting away" or cachexia is a serious issue with cancer treatment so THC has a role there and CBD counters many of the negatives of THC, hence the original meaning of the "entourage effect".
Work with your doctor of course. We'll leave off the cancer-fighting effects of THC since we can get those without the baggage from CBD more cleanly. Same system…one pushes in one direction (THC); one supports works like a feedback mechanism when low (CBD).
We'll take the latter but THC has a role for appetite and maybe pain (but not sleep..interrupts sleep architecture).
Learn why CBD is a must with cannabis or THC.
That's a wrap.
Other interesting players we're keeping an eye on but are not ready for prime time.
Till then, this is our cancer toolkit! Fight the good fight. Work with your doctor. Win!
]]>
Every cell in your body has receptors. It's not just muscles and libido!
]]>
We're going to move away from libido and muscles for now.
Testosterone is so much more when you dig into the research.
Then, you look at how it drops roughly 1% from age 20 and you're wondering why everyone over 40-50 is not supporting this critical pathway.
Worse yet…the average T levels for a 20 year old have dropped in half over the last 20 years.
This is true for almost every age band and we'll discuss why below.
Our focus is going to be on every other aspect of health though:
We'll also look at studies in 2013-2014 that just doomed the general reception for testosterone support and why they were so so flawed. Very similar to the 2001 WHI estrogen study for women.
These are the areas we'll cover:
Let's get started!
T belongs to the class of steroidal hormones. Technically, it's an androgen which just means…pro-growth.
All our steroidal hormones come from a cascade that begins with….LDL…yes, the so-called bad cholesterol.
We have a big review on pregnenolone but both it and DHEA have interesting longevity effects (we'll cover later).
There are also fascinating studies where cholesterol levels normalize when pregnenolone is supplemented.
Watch this little trick:
https://pubmed.ncbi.nlm.nih.gov/21407165/
Essentially, by directly supplementing steriodal hormones (HT), total cholesterol dropped from 228 to 183. It was more pronounced in men.
Most interesting, LDL dropped (with triglycerides)...but not HDL.
Hmmm…it's almost like elevated cholesterol (LDL specifically) is just a work-around the body is doing to get ahold of more steroidal hormones.
So billions of dollars are spent on statins to squash cholesterol without addressing the core reason the body is elevating to begin with? We digress.
So…why is the body so anxious to get testosterone levels back up? It just for reproduction, right??
No!
T (as well as estradiol and progesterone) has receptors on EVERY cell of the body and brain.
Heart. Bone. Organ. Brain. Immune. Every cell.
Why?
Testosterone (like estrogen) is the repair, replenish, grow agent in the body.
It's fighting back against a range of assaults and related damage/deterioration!
We're going to see specifics by area below.
T is as close to the fountain of youth that we have.
And it's quickly going away (maybe by Nature's design).
With a little help from us. Let's go there now.
It's not looking good on the T front.
https://academic.oup.com/jcem/article/92/1/196/2598434?login=true
So from 501 to 391. About 20% drop. It's only gotten worse..
The 2016 study showed another 25% drop. It's declined further since:
Keep in mind that this applies to adolescent and young males as well.
They also took into account BMI, smoking, and other facets that directly affect testosterone.
So…what didn't they take into account?
We are surrounded by chemicals that suppress testosterone OR are estrogenic (which opposes testosterone).
The biggest culprit in our opinion??….the change of fat to seed oils with high Omega 6 content. We did a massive review on seed oils including steroidal hormone effects but the net net…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312216/
The key fat in omega 6 (and virtually all processed food with seed oils)...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846030/
Our intake of seed oils as a percentage of total calories has exploded…roughly over the same time that testosterone has been dropping.
In fact…T levels in 1924 were about the same as in 1987 which is a good 20 years after soybean oil became the defacto source of cheap fat. (please read the review…T is just the tip of the iceberg).
Hmmmm. Interesting hockey stick there for "vegetable oils" with an explosion around 2000.
That's the easy culprit.
Then you have all the chemicals that are estrogenic and hormone-disrupting:
We could go and on. Here's a good example of the skin care product:
https://www.tonyrobbins.com/health-vitality/are-mens-health-products-safe/
We're inundated in testosterone poison.
So…let's start to dive into why this matters.
First…to the brain.
We'll start with the sledgehammer. Serotonin.
Serotonin is the manager of ALL human behavior. Point.
Sure libido but also:
Serotonin is the target of antidepressants called SSRIs which boost it until they build tolerance (see SSRI review).
Turns out…we have a natural antidepressant that's dropping 1% each year from age 20.
Here's where it gets really interesting.
In the brain, testosterone is readily converted to estrogen due to a high level of aromatase in men.
Estrogen directly drives serotonin levels.
In fact (strange fact)...estrogen in the male brain is the real driver of libido!
Testosterone is more tied to aggression and drive.
https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression/
Let's look downstream at the most powerful player in all mental health and addiction…BDNF (our brain's fertilizer).
Ah ha…
https://www.sciencedirect.com/science/article/abs/pii/S000689931400242X
Remember…we said T was the repair/replenish pathway after damage great (stroke) and small (stress).
You can't get to BDNF without serotonin which manages it. Check out the review on BDNF…it's really the superstar in the brain!
So…anti-oxidants, BDNF, and brain growth. Male!
This is all well and good but does it translate?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583468/
Hence, the term..."Mani-pause".
Okay…what about anxiety?
First, a quick note. Cortisol (our stress hormone) just kills testosterone.
Makes sense…danger out there….not a good time to reproduce.
A study looked at the effects of supplementation for men with low T versus placebo:
https://academic.oup.com/jcem/article/81/10/3578/2649928
This was all about bringing T levels up to a normal range! Going further did not help.
T is a major mood manager - anger, irritability, sadness, tiredness, nervousness.
Really…friendliness!?!? Sense of well-being?
Just for reproduction folks.
Most people assume that T replacement will make us angry, irritable, and aggressive.
That's from the old "Anabol" days of steroid use to get levels way above normal. Superphysiological!
We know from above that many (maybe most) men are actually way under normal.
That's tired, irritable, depressed, nervous, etc.
We could go on and on. Let's turn to immune function.
Testosterone and estrogen are both huge drivers of immune function. Interestingly, women have progesterone to push back on estrogen.
Men don't have the same levels of progesterone (although we have some and receptors on every cell!) so T is more nuanced here.
Otherwise, you would see autoimmune, inflammatory diseases, etc.
First, we know that T directly drives immune function as shown by the most recent nasty experience:
https://www.frontiersin.org/articles/10.3389/fendo.2021.694083/full
Vitamin D and estrogen are similar (both steroids!!).
18 fold increase in mortality. 230ng/dL isn't even baseline levels (which we'll discuss later).
The key takeaway with this complicated system…
https://www.frontiersin.org/articles/10.3389/fendo.2021.694083/
Here's the strange part…T can both calm immune function and boost it in males. Selectively!
For example…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075254/
There, it's calming the response when hyperactivated!
The important takeaway…
It manages rather than just push/pull in one direction.
That may be why women get hit with 80% of autoimmune as progesterone (calms the immune) leaves the scene during 40's leaving estrogen (boosts the immune in one direction).
What about cancer which is governed by the immune system (cellular birth/death cycles)?
We'll get to the prostate question later (big news there lately) but what about cancer in general with low T?
There are clues...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424192/
Hypo means low T.
And...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424192/
Okay…none of this makes sense since the general take out there is testosterone=cancer.
If T modulates the immune system and this system detects and removes faulty cells (with oxidative stress)...we need more data.
There's actually a clinical trial right now so we look forward to that detail.
Again…we're talking about bringing low T levels up to normal levels….not excessive amounts. And bio-identical!
After all, cancer is clearly age-dependent and T's dropping 1% each year. Big review on cancer here.
Let's turn to the heart.
If you take T, you'll get a heart attack in a fit of rage. Oh, please.
There is are a range of benefits from testosterone supplementation WHEN LOW for many facets tied to cardiovascular health.
Still, there's is debate on testosterone and cardio risk.
Let's cut through it a bit.
First, hypogonadism….low testosterone.
https://eje.bioscientifica.com/view/journals/eje/165/5/687.xml
They also found that replacement therapy was tied to much better results on treadmill tests.
A study looked at men who had erectile dysfunction as a result of cardiovascular disease. Their primary goal was to see the effect on ED but they also tracked a range of cardiovascular markers:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403087/
Okay…
Goodness. The HbA1C is the big one in our book.
Check out Dr. Attia's podcast on testosterone replacement. Excellent resource.
Inflammation and metabolic health are finally gaining ground as the core driver of cardiovascular risk.
Another study:
https://www.sciencedirect.com/science/article/pii/S2589790X21001335
So..the lower T, the higher the risk even when other comorbidities are taken into account.
Another big study on veterans:
https://www.ahajournals.org/doi/10.1161/JAHA.120.020562
Supraphysiological (much higher than normal range) is risky. Hence, the bodybuilder issues. Synthetics are an issue as well. We can blame them for much of the poor advice and warning around T for decades.
The newer research is showing reduced risk of normal ranged testosterone and cardiovascular.
Another study looked at testosterone supplementation versus control:
https://www.eurekalert.org/news-releases/796591
We'll stop there. Clearly, T is critical to the working of our cardiovascular system.
Let's turn to metabolism (which feeds directly into cardio).
As much aesthetics as health, metabolism deteriorates as T leaves the scene.
Connected?
Let's look at T and the following:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154787/
Goodness. A few notes.
First, "long-term". We don't want the body to push back against T in the form of tolerance. This happens with super high levels (bodybuilders)..hence breast, etc.
All facets improved:
Also, markers for diabetes (metabolic syndrome) improved as well!
Keep in mind that obesity or fat tissue itself suppresses testosterone function!
Fat tissue is not just a store of energy. It actively converts testosterone into estrogen:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770848/
That's why men will gain breasts if they become obese.
So…it's a vicious cycle. Weight gain will suppress T (converting it to estrogen) which then causes more weight gain.
One of the biggest signals for cardiovascular risk in men is belly fat and fat around the organs. Visceral fat.
https://academic.oup.com/cid/article/37/Supplement_2/S142/335512
That brings us to insulin and diabetes.
We'll jump right into the primary driver of diabetes and metabolic dysfunction.
For men…
https://www.frontiersin.org/articles/10.3389/fendo.2019.00090/full
The entire metabolic system! Fat. Insulin. Sugar. Goodness!
We say "men" because it had the opposite effect on women!
When doctors block testosterone function due to prostate cancer, what is the result?
A huge increase in diabetes!
https://joe.bioscientifica.com/view/journals/joe/240/3/JOE-18-0573.xml
Let's turn to old tread.
We've covered this a bit up top. Remember…LDL is the sole source of all our steroidal hormones and judging from above, T's pretty essential!
So…
https://www.sciencedirect.com/science/article/pii/S0022227520345144
"Antiatherogenic" means anti-arteriosclerosis. Less build-up in arteries. Hmmm..
All facets improved.
What about the real enemy…sugar.
A German study looked at T in addition to medications for Type 2 diabetes versus control:
https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.14122
This was a long, 11 year study!
1/3rd saw remission. There's that HbA1c (marker for sugar excess damage - see our review on the problem with glucose).
Funny that HbA1c is also the gold standard for cardiovascular risk (see the glucose review!!!).
We'll get into why T keeps glucose under wraps below with the powerful AMPK pathway (key to longevity).
Remember way above how low T was tied to "tiredness" and T replacement resulted in more energy?
Metabolism is all about energy. Using it. Storing it. Transportation.
The enemy of everyone over age 40ish.
Fatigue.
T's a big player there.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823386/
Okay…the total score for that test is 63 (9 questions; 1-7 score each).
A nearly 15 point drop is huge!
That was a 1 year study but keep in mind that it can take 18 months or more for T's effects to fully integrate (as per cardio studies).
What's driving this?
First, testosterone governs glucose (energy) uptake into muscles and bones. That's partially why it's not floating around in your bloodstream doing damage (insulin, etc).
But it goes deeper. Remember that T is the replenishment pathway.
Mitochondria…the literal energy plants of every cell in your body. Ancient bacteria we kidnapped…or "negotiated with" to power all multicellular life.
More on mitochondria function here.
T directly supports their function!
First…the broad strokes:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921852/
Goodness. We're talking about energy production AND the management of our epigenome (see editing your health code to learn why this is so important).
Love this study.
They blocked testosterone in mice and saw the following in the brain:
https://www.hindawi.com/journals/omcl/2017/1202459/
Literally…shutting down key parts of energy production in the brain.
They then supplemented D and the energy production came back online.
One note…when mitochondria aren't functioning correctly, you have a range of issues such as oxidative stress and inflammation. Not to mention…low energy system-wide!
Low mitochondria function is tied to aging and many aging-related diseases.
What a great segue.
We did a big review on steroidal hormones and longevity.
Let's zero in on testosterone.
Just logically, all the attributes we mentioned above (which are reversed by T supplementation) are tied to aging:
Let's zero in on key longevity pathways and see if T is involved.
We'll focus on the following first:
First, AMPK.
An interesting study looked at T supplementation's effect on AMPK for men with low T.
The results:
https://www.researchgate.net/publication/338082470
Here's the deal.
Men with low T show reduced AMPK activity in muscles and fat. After T, sugar is "brought" into this tissue (rather than being free-floating) and increasing AMPK.
This is thought to be the main driver behind improved glucose and insulin effects from T which we looked at above.
AMPK is a nutrient sensor so this makes sense. Learn all about AMPK and longevity.
Then there's SIRT.
A study looked at how T replacement protects against cognitive decline (ding ding ding…aging!)
Hello SIRT:
https://pubmed.ncbi.nlm.nih.gov/22238626/
Learn all about SIRT at our pterostilbene review or CBD and SIRT.
There's lots of conflicting information on T and longevity. First, we need to sequester just data on replacing T for LOW or hypofunction.
Going above the normal range is just as bad as being below.
Range bound.
Too low is bad:
https://pubmed.ncbi.nlm.nih.gov/27734705/
We look forward to larger clinical trials but this synopsis sums it up:
https://www.worldhealth.net/news/can-men-live-longer-taking-testosterone-therapy/
The key takeaway is what happens when we supplement for men with low levels:
https://pubmed.ncbi.nlm.nih.gov/25892327/
Let's break that down. Basically, supplementing T increased survival rates and brought them up to men with…normal T levels!
So the goal is…normal T levels. Go get tested. Good luck with that based on the worldwide drop over the past 40 years.
Check out the Steroidal Hormone and longevity review for lots of research!
Let's turn to the boogeyman.
The original big fear around T supplementation revolved around two issues:
The studies that drove this fear (2013/2014) were deeply flawed…at best! Check out Dr. Attia's review of them.
Most of the prostate issue centers on DHT levels.
DHT is a much stronger version of testosterone. It spikes during puberty to "masculinize" the body and brain.
Boys to men…although DHT would not make you a fan of the band.
Both testosterone and DHT operate on the androgen receptor but DHT is much stronger!
https://www.healthline.com/health/dht
As such, DHT drives growth but actually causes male pattern baldness (or may result from damage there…interesting new research).
Prostate cancer is a bigger issue as we get older.
Here's the strange piece. Prostate cancer risk increases as we get older when T is going down!! Almost entirely tied to old age when T is at its lowest.
Hmmmm.
We wouldn't be surprised if DHT is just a work-around by the body to make up for the loss of…Testosterone!
Average onset of prostate cancer is 66.
Look at the drop T levels:
https://eje.bioscientifica.com/view/journals/eje/173/6/809.xml
Huge drop right around 60-65. Hmmm.
What's interesting is that DHT doesn't drop much there. Remember…it's like 5 x T in terms of effect.
So the body is making up for loss T with increased DHT as a percentage of total androgen!
Very similar to what it does with cholesterol levels (the source of all steroidal hormones).
The anti-balding and prostate meds all block the conversion of T to DHT.
Ah ha!!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035750/#R34
T's important. The body will switch to DHT to make up for the loss (as in getting older).
So…the million dollar question…does T supplementation increase prostate risk as was blasted on headlines from the 2013 study?
A shift is afoot:
https://www.liebertpub.com/doi/full/10.1089/andro.2020.0013
PCa is prostate cancer androgen gene, a risk factor.
Or..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375443/
Or…
https://www.nature.com/articles/s41443-020-00387-3
Wait a minute…using T to TREAT aggressive prostate cancer?
There's still a black box warning on T replacement around this issue. Most doctors are not keeping up with the newest data.
Pumpkin seed oil is a natural way to block the conversion of T to DHT by the way.
Let's turn to the safety and practical questions learned the hard way.
So the big issues in those flawed 2013/2014 papers were around prostate cancer and cardiovascular risk (primarily heart attacks).
We've already looked at the prostate. What about cardiovascular beyond all the positives we see around metabolic, blood pressure, glucose, cholesterol, HBa1c, etc?
We have to look at new research which if finally getting to the bottom of this. Again, it comes down to level.
If levels are low, replacement is beneficial!
https://www.eurekalert.org/news-releases/796591
And go figure:
Maybe, they'll remove that ridiculous black box soon:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164696/
Keep in mind that the benefits of testosterone replacement for cardiovascular function takes time…18 months in some studies.
3-5 year studies show profound effects so studies that look at 8 weeks or less did nothing to help the cause of understanding risk.
So…all this is around replacing T when low.
What's low?
Technically, it's under 300 ng/DL for total testosterone. Age drives the range quite a bit but like estrogen, do you really want 70 year range versus say 40?
"Normal" generally falls between 300-1000 although some men naturally go much higher.
Get tested. A good range is 500-800 as a baseline for replacement. Watch symptoms. Mood. Energy. Strength. Use those for signals for your body's particular "normal" range.
There are many facets driving testosterone function such as MAO which breaks down testosterone levels.
Vitamin D is also a key player in steroidal function and so many people are deficient. Aim for 50-70 ng/ml. It's a steroid itself!
Then, there's the type of T:
Our experience??
Topical is not great at getting into the blood. Lost 2 years doing that.
Shots require constant visits and the levels ping/pong between super high and super low (relatively speaking). That doesn't match the natural daily release of testosterone (early mornings).
Under skin implants dissolve more slowly but you have less control over levels.
Oral doesn't work well with T since it's hard on the liver.
We finally settled on sublingual daily T at 100mg. We get bioidentical T through a compounding formulary at about $75/month.
The levels have come up quickly (30 days) from about 200 to 500+.
The bioidentical is really important since synthetics never work as well and have their own risk profile (learned this the hard way from estradiol/progesterone reviews).
For now, this is the best approach we've seen.
Take T in the morning since it is stimulatory even though it improves sleep long term (the estrogen to serotonin to melatonin pathway in the brain).
That's a wrap! T came on the scene about 500M years ago. It's only in the last 20-30 that we have options to keep this repair/replenish pathway functioning as we get older!
Big review on Cold Exposure coming which may naturally boost T (and LH) significantly!
Steroidal hormones and longevity
]]>
101 things you want to know about CBD and anxiety pathways. It's ridiculous!
]]>If you're looking for "anxiety bad" fluff, this ain't it.
Below is the result of 100's of deep reviews and a million+ words on NIH research around CBD and anxiety.
But in bite-size, easily digested nuggets (no Klingon!!) with links out to deep dive if you brought your snorkel.
100+ helpful items so a way better value than the 20 nugget variety!
Anything and everything you wanted to know about how CBD affects anxiety.
Your cheat sheet if you will.
Links will be sprinkled throughout to supporting, detailed reviews with tons of NIH research so you know we're not just throwing darts at a board. Below is the easy version!
Let's get to it! We'll start some big hitters and then go free-range chicken from there.
One note…make sure not to miss the last one…it's really the crux to fixing anxiety long-term based on all the new research.
Go get a coffee. Enjoy! You're on the path to calm.
GABA is the brain's "brake" pedal with direct impact on anxiety, sleep, and pain. Don't take our word…some of the biggest meds on the market pump up GABA for anxiety and sleep with the benzo's being front and center.
Problem is they build tolerance really fast (about 2 weeks) and have a nasty addiction profile. Hence the street names and values for Xanax and Ativan.
If we want to calm anxiety, GABA is our NOW best friend. We'll see below all the different things that can exhaust GABA and the tools to support including CBD.
CBD directly supports GABA…when LOW!
The "when low" part is why we don't see addiction, tolerance, or withdrawal with CBD. We'll see studies that support this below.
Just know that the GABA effect from CBD is fast…about 12-30 minutes depending on how you take it. Tricks below to speed that process.
Serotonin is your stress response buffer among other things. In fact, it manages all human behavior (including self-esteem and confidence). When serotonin gets exhausted, anxiety becomes more entrenched and there's lots of hits coming to serotonin from many places.
We'll look at how to reduce those hits and support serotonin. CBD also acts like a feedback mechanism for serotonin when it's out-gunned. This is critical because too much serotonin is even worse than too much.
Serotonin syndrome from SSRIs is an example and it's brutal. Plus, they build tolerance. We'll see how they really work below and it's all about brain repair!
For now, just know that CBD supports serotonin and that effect can take about 2 weeks to really build up (more below on why that is...so important!).
Okay…two big hitters that you'll see referenced over and over below. Let's spread our wings a bit.
No, not the Swarzenneggar kind (sure…he was "natural")!
Estrogen, testosterone, and progesterone are huge players in anxiety.
Estrogen and testosterone directly support serotonin (the "feel right" player)
Progesterone directly supports GABA (the "feel calm" player)
Here's the rub…
Progesterone and testosterone drop about 1% every year starting around age 20
Estrogen goes into a spiral for women in their late 40s
Hence all the prescriptions for benzos and SSRIs (plus a boat-load of alcohol which boosts both GABA and serotonin but with nasty tolerance).
Get your levels tested. Support with bioidentical if possible. It's how we found CBD to begin with after a brutal perimenopause (Dre's story).
Outside of trauma/infection (even early in life), this is probably the biggest culprit out there for anxiety and depression.
Hold CBD oil under your tongue for up to 60 seconds (the longer the better).
This allows CBD to get right into the bloodstream and avoid the brutal gut where most is lost.
Studies show this can boost "bioavailability" by up to 4x's!
It also speeds how fast you'll feel the effects of CBD with estimates around 10 minutes…much faster than the 20-30 minutes on average when you ingest.
More importantly, we essentially saving 75% on CBD costs by doing this.
This combined with further tips below can really boost the amount of CBD that gets to work on anxiety.
It's also great if something stressful is coming up fast (heading to a date, presentation, interview, etc) in the next 20 minutes!
Absolutely love this study!
To set it up, they looked at how CBD would affect systems tied to anxiety after an injury.
Serotonin manages our pain thresholds and it will exhaust with intense or chronic pain taking everything else that serotonin does with it.
The results:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
Don't worry…we always translate. Family means no one is left behind :)
CBD had the following effects:
The most important word there is "rescue". Not boost or pump up.
Rescue. We see this across the research along with words like normalizing or modulate.
We don't want to push serotonin too far up or you start to get really nasty side effects. CBD "rescues" when exhausted!
What about its cousin? THC
You know that cousin you have…where there's just nothing in common?
That's CBD and THC.
In fact, the godfather of CBD, Raphael Mechoulam, coined the term "entourage effect" to reflect how CBD countered many of the effects of THC.
THC pushes a very powerful pathway (CB1) in one direction. Longer term, this causes tolerance which means we lose our natural production of that pathway with time. More on IT below.
CBD supports that pathway when low by blocking the chemical that slows it down called FAAH.
In fact, CBD may be very helpful for cannabis addiction and withdrawals!
For anxiety, THC is a big wet blanket but it comes with a hangover of sorts (the opposite of calm if you've ever noticed).
About 33% of the population also has histamine (allergic) reactions to THC and as we'll learn below, histamine is just a different form of anxiety when jacked up!
We're not anti-pot people (hello, CBD!!) but longer term, CBD is the better fit for anxiety
Deep dive on CBD versus THC.
We need to set the table here because you're going to see this over and over (till we beat it into your anxious head :)
Outside of loss of hormones (gradual or otherwise), early trauma/infection/stress (even in utero) is probably the biggest player for anxiety later in life.
Our bodies keep a "record" of past trauma and a study showed it can go back 10 generations!
Yes, you're carrying your parent's baggage like it or not.
Studies showed that descendants of people who were in World War II concentration camps had increased stress response markers.
Stress is a huge player with anxiety (duhhhh) as we'll see below.
A lot of what we talk about later deals with "editing" these system updates that directly affect "trait" anxiety.
It's mainly "recorded" in the immune system of all places but there are tools and tricks to overwrite this…including CBD!
CBD is a powerful editor…the MS Word of immune response along with psilocybin which will revolutionize mental health when finally available.
For now, just make a mental note..early trauma/infection has the following effects:
We'll be talking about all of these below since this is CBD's wheelhouse.
Let's check that house out now.
How exactly does CBD work for anxiety?
Hello, anandamide!
We have an entire system (endocannabinoid) which is tasked with balancing other key systems (maybe every system) including:
Goodness!
One of the 2 big players in that system is called anandamide, named after the Hindu "bliss" goddess Anand.
3 guesses what IT feels like.
This is the "high" behind THC or even the runner's high (sorry endorphins) and even orgasm.
Yea…so that.
CBD supports anandamide when running low by blocking FAAH (from above).
This is a perfect interaction since anandamide is our backup, backup stress response buffer behind serotonin.
Call in the cavalry!
Anandamide is a sledgehammer to anxiety and we can use CBD as a
rubber mallet to put it back in place so we don't exhaust it!
Probably our biggest pet peeve!
There's so much misinformation about the best type of CBD for anxiety.
Full spectrum is generally CBD with all the plant material and/or other cannabinoids (CBG, CBN, CBC, and small amounts of THC) added together.
CBD isolate is…CBD by itself (generally in a base oil).
Here's the rub…40-60% of the population has histamine issues and that number goes up for women (thanks for nothing, progesterone) and as we get older
All that plant material from full spectrum is going to feel pretty…well…anxiety ridden for these people!
You see it in our reviews all the time…people who see anxiety get worse with full spectrum and that goes away with isolate.
We did big reviews on CBD versus CBN and CBG. The issue is that they are "agonist"...push in one direction like weaker versions of THC.
Longer term, we want ZERO tolerance or were actually going backwards.
The histamine piece is the bigger issue though for anxiety as we'll learn below!
The above is all well and good but what about studies on people?
Okay tough guy!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/
That was actually a big sleep study (GABA manages sleep as well hence the Ambien craze) but the primary target was anxiety.
CBD isolate by the way (as is 99% of the actual NIH research).
The last one is important since studies show that peak neurogenesis (brain repair critical to anxiety longer-term) is around 300mg.
We'll touch on this whole process below since it really the "man behind the curtain" with mental health including anxiety.
Just put a note next to "BDNF".
Test how CBD feels on your system and adjust accordingly.
Studies on more serious issues from schizophrenia to opioid withdrawal (just a bit of anxiety) are around 600-800 mg daily and CBD has been tested up to 1500mg daily with a strong safety profile.
This goes back to how it works to support the balancing agent in our body…when low!
Newer research is really pointing to the gut for things that occur in the brain such as anxiety!
Inflammatory states in the gut act like a thermometer for the brain via the vagus nerve.
In fact, most of your serotonin is actually made in the gut…also called our "second brain" with the most neurons only second to our brain.
The real exciting news is around the microbiome or bacteria that inhabit that gut.
Some have immediate effects on anxiety such akkermansia (ridiculous little player for metabolism, mental health, and gut function).
People with obesity have zero akkermansia! Check out our reviews on metformin or berberine for more info.
Starting to think it's all gut biome!
As for anxiety:
https://www.nature.com/articles/s41598-019-40140-5
CBD directly calms gut inflammation and protects the all important barrier between it and our body (brain). Check out CBD and probiotics for anxiety to learn more.
Talk about torture.
Researchers took people with diagnosed social anxiety and then put them through a public speaking test.
Jerks!
Did you know that fear of public speaking is more prevalent than fear of death?
Now throw in social anxiety!
Okay…the results with 600mg of CBD prior:
Interesting Items:
Big mic-drop moment:
SSPS-N is a Negative Self-Statement test to reflect a person's own judgment on themselves.
Essentially…how do I see myself up here on stage speaking in front of others.
"Abolished". People with social anxiety saw their "performance" the same as those without social anxiety.
Goodness. So…going on a date, playing in a big game, interview. The full review of CBD and public speaking.
In bed? See CBD and premature ejaculation or CBD and performance anxiety for deeper dives.
The liver is the enemy.
Not really but when it comes to CBD, the gut and liver significantly reduce the amount that gets into the bloodstream where it gets to work.
We mentioned the under-the-tongue trick above but another key option is to take CBD after food.
The liver is busy processing our food…especially fats, and this allows more CBD to get through.
This is part of our "increased by 4x's" suite of options to get more CBD into play against anxiety.
Taking CBD after meals directly increases how much shows up in the blood.
BDNF is basically Homelander on The Boys towards anxiety.
But less psychotic maybe :)
It's short for brain derived neurotrophic factor.
Essentially, the brain's "fertilizer" and when they dig deep into how SSRIs (or CBD for that matter) works, it's all about BDNF and neurogenesis (brain repair/replenishment).
You're going to see this over and over below because there's a battle going on in your brain.
On this side (cue cheesy announcer voice):
And on this side:
So…BDNF!
Yes…it's that big of a player and we'll cover it in detail.
As for anxiety??
https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00709/full
2020 paper. Lots of goodies here.
Wow…more severe early life stress (maternal separation in this case) leads to worse and worse mental health issues…and medical!
Don't worry…we'll look at how to unwind this below (hint hint…the immune system).
As for CBD:
So…good stuff? Make a checkmark by BDNF.
Mag is awesome for anxiety.
It acts like a mineral-based stress buffer with big connections to anxiety. Unfortunately, our body has a weird quirk where it will dump out mag via urine when under stress.
Great.
Signs of low mag:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761127/
Glycinate versions cross the blood-brain barrier much better which is key to anxiety and the nervous system.
Monster review of mag for anxiety, migraines, sleep, and more.
We take 3 x 100mg daily and as needed (stressed to the gills or middle of the night).
We need an introduction since the players are going to keep cropping up.
You could say there are two brains in your head:
Don't glaze over…we'll walk you through it.
The snapshot:
.
Think of a tug-of-war between our rational side and our fear side. If the rope starts moving to the amygdala (fear/emotional center), everything will be "colored" with anxiety.
Anxiety is a reflection that one side is winning (we'll let you guess what side).
Remember above how BDNF (brain's fertilizer) went down in the prefrontal cortex after early life stress?
Hmmmmmm.
This is the "circuit" for anxiety with the hippocampus (mood control/memory) playing a switching roll. It's also very dependent on BDNF since it's always changing (memory formation).
We've been talking about neurotransmitters and "messengers" till now but longer term, if the crosstalk is skewed, you see actual changes in the brain architecture and communication.
CBD's effect there?
https://www.technologynetworks.com/neuroscience/news/cannabidiol-significantly-improves-blood-flow-to-brains-hippocampus-new-findings-show-338619
Okay, and what about brain repair?
https://link.springer.com/article/10.1007/s12035-018-1143-4
Goodness…we're going to drop the mic a second time (after the public speaking one). Mic's about to break.
CBD boosts BDNF (brain repair) in the prefrontal cortex.
And the hippocampus (very vulnerable to damage)?
CBD was shown to reverse the damage from long term THC (cannabis) use on the hippocampus via neurogenesis.
Related:
Mindful meditation, exercise and CBD for hippocampus repair
Okay…let's come for air a bit after brain surgery.
Benzos are the primary class of meds for anxiety. The pump GABA in one direction.
Hence the fast tolerance (about two weeks) and with a little spike of dopamine, they also drive a pretty nasty addiction.
Ativan and Xanax are the worse in this respect:
You're going to feel really bad when they drop off.
Hence the street names and values for these two drugs that are handed out after about 10 minutes with your "doctor".
We did deep dives on CBD versus benzo, CBD versus Xanax and Ativan, or how we used CBD to taper off benzos.
Unfortuantely, benzos are the go-to for anyone who's anxious these days.
Read the detailed review above to understand the deal you're about to enter into. Lots of research.
Does CBD do the same thing?
It supports GABA when low but it doesn't spike dopamine (in fact, studies on schizophrenia shows it balances it in different areas of the brain simultaneously).
It also doesn't build tolerance or cause withdrawals. This is really the beauty of how it works in the endocannabinoid system unlike other cannabinoids (THC, CBN, Delta8, etc).
Feedback mechanism when low. Nothing when higher. Benzos are going to be the new opioid epidemic and we'll look back with the same surprise and disbelief of how we got there.
The pandemic didn't help much. Check out the review. Understand the mechanism. Be informed!
Your primary stress hormone.
Cortisol directly counters GABA in a delicate dance for sleep/wake and stress/calm.
Too much cortisol (stress), and GABA gets exhausted with the result being anxiety.
It's important to understand that our endocannabinoid system is tasked with pushing back when stress and cortisol levels rise!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871916/
Translation, please!
When stress (cortisol) spikes, the endocannabinoid systems is triggered to counter the spike in the "fight or flight" area of the nervous system (HPA). And end the stress response!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
So when stress was overwhelming, CBD calmed the release of cortisol (our primary stress hormone), especially in context of anxiety!
Stress unchecked IS anxiety. One note…THC can actually cause anxiety.
In that same study above, they looked at THC and stress specifically.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
CBD actually blocked this effect in those people which goes back to our whole "entourage effect" deal from above.
What gives? This doesn't make sense as many people use cannabis to "de-stress".
Our bet is on the histamine piece! Histamine is excitatory in the brain (eats up GABA which is trying to counter cortisol), and for the 33% of the population allergic to THC, it's going to be…anxiety ridden.
Check out why CBD is a must if you use cannabis or CBD and cortisol.
Here's the secret sauce..
Peak CBD in the bloodstream is about 4-6 hours taking it.
This coincides nicely with meals and there's an added benefit there of keeping the liver busy so more CBD can get through.
So…taking CBD after meals and at night as needed can be a successful approach.
For example, if you want the 300mg daily for peak neurogenesis (brain repair), 100mg after meals takes into account both the liver piece AND provides a more consistent level of CBD in the bloodstream.
Everyones is different and some people use CBD as needed (in stressful situations) or once a day (say before bed or in the morning).
See how often you should take CBD for more.
That brings up a great point…
Many people are hesitant about CBD because of the track record of cannabis (THC).
Does CBD affect how you think or your ability to use heavy machinery (funny that's always the warning across many meds…who's using all the heavy machinery these days??)
The good news…
CBD can actually make you more alert (but not anxious) during the wake cycle.
And sleepy during the sleep cycle! Again, the endocannabinoid system is tasked with "balancing" this clock.
The public speaking study above showed no difference cognitive function (ability to think or speak) aside from the benefit of not having extreme anxiety!
Check out CBD in the middle of the day for more info.
CBD also doesn't sedate like anti-anxiety meds or anti-histamines.
Speaking of histamine…a quick but important detour.
No one thinks about histamine and anxiety.
Big mistake!
In fact, the first class of anti-anxiety meds were…anti-histamines!
Hydroxyzine comes to mind and God knows how many people (women in the 40's/50's) take Benadryl or Tylenol PM for sleep and calm.
Here's the rub…histamine, aside from allergic reaction manager, is excitatory in the brain. Eats up GABA (key to sleep and calm).
The problem with the Benadryl class (anti-histamines) longer term is that they rip acetylcholine, the "calm and focused" neurotransmitter.
Also critical to risk for dementia and brain fog.
Can't do that long term. What about CBD and histamine?
CBD supports anandamide which is a powerful calming agent for histamine release. Lots of research on CBD and histamine here.
What about acetylcholine since it's so important for the "rest and digest" system (calming)?
https://pubmed.ncbi.nlm.nih.gov/29876791/
That's the "wake" piece during daytime but we know it helps with sleep during nighttime.
The beauty of the endocannabinoid system…balance.
Deep dives at CBD versus SSRIs or our Top 10 tips for getting off SSRIs.
Here's the deal…SSRIs boost available serotonin in the brain.
We know serotonin is a master regulator of ALL human behavior but more important to our discussion, it's a huge stress response buffer!
Stress on steroids is anxiety.
The problem with SSRIs is that they build tolerance with time.
This means your natural serotonin levels go lower so the drug has less and less effect on most people.
Your "safety net" just keeps dropping and coming off of SSRIs can be brutal!
Are there ways to support serotonin without this tolerance effect?
Of course, CBD is an allosteric positive modulator which means it supports serotonin…when low!
That's why we don't see serotonin syndrome, tolerance, withdrawals, or the downright bizarre side effects that SSRIs can have.
Learn about CBD and serotonin or CBD versus SSRIs
Let's look at brand new data please!
There's interesting research lately on how building iron levels in the brain/body as we age can be toxic.
A study looked at CBD's effect after this in a very important brain area for anxiety…the hippocampus (our mood manager).
The results:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917759/
Basically, too much iron can damage the brain, especially the hippocampus which governs mood switching.
CBD offsets this and even calmed activity on a specific pathway (Dnmt3a) that's tied to anxiety states.
Check out CBD and the hippocampus (just the mood switch..that's all)
Get your levels tested!
So many people are running around with low levels and Vitamin D is a huge player in mental health including anxiety (see Vitamin D guide)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667301/table/brb31760-tbl-002
We have a giant review on Vitamin D and mental health.
A study looked at differences in anxiety, depression, and stress for pregnant women and found the following:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089018/
So, for every drop of 1 ng/mL, scoring for anxiety and stress went up almost ½ a percent. The score range is from 0 to 63 (worse).
10 ng/ml (very easy to swing on D levels) about 2-3 points! If you go from 30 to 60, that's about 8 points. Big deal out of 63!
Get your levels tested and read the guide.
Call it irrational if you want but I have an intense fear around my eyes.
Getting poked, etc. Maybe a past life.
Either way, we all have specific fears, perhaps related to past experiences (mini-PTSD) that are "locked" in. Like writing in wet cement.
But are they?
There's a fascinating concept of "fear extinction" which deals with overwriting these past connections that have been carved into our brain's jumble.
It's critical to PTSD, anxiety, trauma, and a range of issues.
Psilocybin is a monster player in dislodging these phantom fears but CBD's a slower, more methodical actor.
To wit:
https://www.frontiersin.org/articles/10.3389/fphar.2016.00493/f
Remember, outside of the loss of steroids, early trauma/infection is a HUGE player in who gets anxiety later in life.
This requires new pathways (BDNF) and fear extinction….both in the purview of CBD!
Check out rewriting your mental health past.
No…beyond the original cause of the anxiety.
CBD doesn't cause tolerance, withdrawals, or addiction…the key drivers of rebound anything.
This is due to how it supports key systems only when running low (or hot in the case of inflammation, etc).
Learn how CBD works but the key take-away is that CBD doesn't cause your systems to push back because it's hitting key pathways too hard.
This is quite a difference from other options for anxiety:
That's why we focus exclusively on tools that don't build tolerance (see Anxiety Toolkit).
Keep in mind that you still have to get to the root of why you had anxiety to begin with (focus on steroidal hormone loss and/or early trauma/infection "markups" via the immune system).
More on CBD and Tolerance
If we're going to tackle anxiety, negative thoughts and rumination needs to be handled side-by-side!
This is the fear side (amygdala) running amok with very little push back from the rational brain.
With a little help from this brain area called the habenula.
It's the seat of DREAD in the brain!
We did a deep dive on CBD and negative thoughts as there's another aspect at play…the default mode.
You know that time when you're just staring off and someone has to same your name twice to snap you out of it?
Past trauma or other issues can distort this setting where it's stuck and negative or repetitive thoughts can be the result.
Studies have looked at how THC can distort this connection setting but CBD restored the correct connectivity!
https://neurosciencenews.com/cbd-brain-impairment-12042/
Salience is how the brain decides what to focus on….the key to kicking negative and repetitive thoughts to the curb.
Check out CBD and negative thoughts or CBD and OCD for more.
There's a lot of confusion on how much CBD generally.
We mentioned above that 300mg is peak neurogenesis and that's the secret star behind mental health.
Studies on withdrawals (opioid and alcohol) actually give some guidance though on levels.
Since withdrawals tend to be the worst in the beginning (generally the first 10 days), those studies were at 600mg daily!
Again, for serious issues, 600-800mg daily matches research. Even the public speaking study was one dose at 600mg.
Based on this, there's an argument for going 600mg daily for the first 10 days and then dropping it to 300mg until there's some relief.
From there, adjust accordingly and look at the anxiety toolkit on ways to address what may be causing the anxiety to begin with (focus on steroidal hormone loss depending on age and early trauma/infection (even in utero).
Work with your doctor/naturopath and take away (at least 40 hours) from any medications.
It's the 10/20 plan! Same for benzo and SSRI tapering.
Remember in the anxiety circuit how the emotional center in our brain called the Amygdala can run "hot" with anxiety?
This area is part of our much older "reptilian" brain. It's there to protect us from danger…a threat detector.
The problem in anxiety results when it's hyperactivated!
A study looked at CBD's effect there directly in response to fearful faces:
https://www.ncbi.nlm.nih.gov/pubmed/19124693/
Blood flow is the "gasoline" of the brain!
SCR is a measure of skin electric activity…a sign that you're in a fight or flight response.
Basically, CBD calmed the fear response!
One note…THC had the opposite effect so careful for all the "you need THC to activate CBD" nonsense out there in the market. Nonsense!
Funny question to us but we're aficionados by now :)
Most people feel something shocking from CBD isolate based on their experience or inference from THC or cannabis.
CBD is not psychoactive! No high or sense of euphoria. Also, no tolerance or reduction in cognitive function.
The general feeling with CBD is as a calming agent. It can make you drowsy but according to the sleep/wake cycle (so at night!)..
The whole point of the endocannabinoid system is to balance other key systems and CBD supports it when low!
One note…this is for CBD isolate. With full spectrum CBD, all bets are off and we see people's anxiety actually increase due to the histamine response.
Don't underestimate the power of histamine to all the plant material in full spectrum. If any brand of CBD doesn't feel right, that's your first ticket (2nd being bad product or contaminants…very common unfortunately).
Check out how will CBD make me feel
Yes! 10-15 minutes immediate.
This is especially true if you hold it under your tongue for up to 60 seconds to absorb via the sublingual gland.
Otherwise, it's generally 20-30 minutes via the gut.
That's the GABA piece and perhaps the reduction in oxidative stress, inflammation (but gut and brain), and cortisol (stress hormone).
GABA's fast!
The longer term player is serotonin (stress response buffer) with its brain building/repair pathways (BDNF).
See how long does it take for CBD to work.
We love glycine for sleep and anxiety. It's a simple amino acid we can supplement which governs the sleep clock but more importantly…
It's a sink for excess glutamate (the brain's "gas" pedal)!!
Remember that early trauma can ramp up inflammation and this means glutamate just gets slathered on.
This eats up GABA (the opposing force) and voila…longer term you have anxiety and just about every mental health issue out there!
Our most powerful detox pathway called glutathione is cooked with three ingredients:
Glycine and cysteine soak up the glutamate and lock it away!
You can supplement but guess what??
CBD boosts glycine WHEN low just like GABA!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301686/
"Positive allosteric modulation" - feedback mechanism when low!
Check out the review on glycine (especially for sleep)
We just mentioned how glutamate is made above.
You need cysteine along with glycine to soak up all that glutamate and make your most powerful detox player.
Hello NAC! (the "c" is for cysteine)
NAC is a powerful detox supporter (they use it for liver poisoning from Tylenol) but more importantly for our discussion…it keeps glutamate in check.
That means more GABA can keep you calm!
We have a monster review of NAC for mental health but the detox piece alone is critical.
Ummm….NO!
First of all, investigations have shown lots of bad data on ingestables purchased on Amazon in terms of fakes, contaminants, etc.
You don't want to buy anything you put in (or on for that matter) your body from Amazon.
There's just too much counterfeit product and a schlocky pair of shoes is one thing….something you put in your body is completely different.
CBD is technically a food supplement so it needs to be 3rd party tested because there's so much crap product out there.
Reading above, you can see there's lots of potential with CBD across a range of pathways. This popularity just calls out the "get rich quick" types with a label and bottle of who knows what.
Third party testing is the way to address this. Find it here.
Technically, CBD is NOT allowed on Amazon any way so any of the "hemp oil" products you find there will probably be pretty questionable.
More at CBD on Amazon.
Yes! Some people take as needed (a stressful situation) while others take it daily to address underlying pathway balance issues.
The key point is that CBD does not build tolerance with daily use.
This means that your body isn't pushing back the other way because it doesn't like how a substance affecting key systems.
The same can't be said for most meds and especially those for anxiety:
In the research with CBD, you see lots of words like "normalize", "modulate", or "rescue" (remember, from the serotonin effect??).
CBD is not an agonist (boost in one direction) or antagonist (reduce in oe direction).
So…daily use is fine. See the article can you take CBD daily.
An interesting study genetically blocked CB1 receptors. This is where CBD and other cannabinoids do their work in the nervous system.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648779/
So…when they blocked the endocannabinoid system, SSRIs lost their ability to work!
Hmmmmm.
Dig deeper into the research and it turns out that neurogenesis (brain repair pathways) is THE key to how antidepressants work till tolerance kicks in and ruins the party.
You need the endocannabinoid system for this whole process!
CBD supports neurogenesis (research above and here) but without tolerance!
Psilocybin is going to be an absolute game changer on this front as we'll see later.
An orgy of neurogenesis.
Check out how SSRIs really work.
We've talked a lot about the brain and neurotransmitters with a slight detour to the gut.
Let's look at the hub between the gut and brain and it's very special chemical messenger.
This is the autonomic nervous system.
Notice how anxiety doesn't seem to be under your conscious control? It's operating in the background without a flipping care as to what you think.
Adrenaline drives the "fight or flight" while acetylcholine drives the "rest and digest" side. Guess which side anxiety falls on??
Okay…this is cool…stay with us.
We know that early trauma/infection can upset all sorts of apple carts.
A study looked at early exposure to bacteria (infection) in utero and acetylcholine.
Bad effects across the board in the prefrontal cortex (the rational player in the anxiety circuit) and the hippocampus (our mood manager).
CBD's impact??
https://ro.uow.edu.au/cgi/viewcontent.cgi?article=2446&context=ihmri
They were looking in terms of thinking (and schizophrenia specifically) but we know from above that anxiety states are also directly managed here!
Check out CBD and acetycholine. We'll check out the vagus nerve below but the part of your nervous system you can't control….can be supported!
Stress is intimately tied to anxiety as we've seen countless times above.
Does CBD affect your stress response?
We'll see your bet and raise you!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
Goodness. Translation please.
CBD supports our primary stress response buffer - serotonin (5HT)
It does this right down to the DNA level to keep stress-effects from causing serotonin to downregulate.
Serotonin is also our pain threshold and sleep manager.
Just sayin'
To take this stress response effect to the extreme…
A study took people with a high risk of psychosis…right on the edge of a breakdown.
They had a health control group, a group treated with CBD, and another group not treated.
The results:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113209/
So, the healthy group did best (expected). The untreated group did worse with stress.
The CBD group was in-between! Keep in mind these are all people with very low stress resilience (high risk for psychosis).
CBD brought this response halfway to normal!
Check out CBD and psychosis for more detail.
Very high anxiety is truly an altered state with almost zero stress resilience. Let's break that down and then work on what's driving it.
Speaking of which….
We have to unwrite the effects of trauma, stress, and infection from early on.
Or we're just spinning our wheels.
To point:
https://www.nature.com/articles/s41598-019-40698-0
We all have something and if we don't…our parents or their parents did. Studies show the effects of trauma can go back 10 generations (at least).
Most of this is encoded in the immune system via the epigenome (the system that controls how, when, and how much our genes are turned on/off).
Studies are now realizing that changes in the endocannabinoid system are also at play.
And then there's CBD:
https://www.sciencedirect.com/science/article/abs/pii/S0278584621002670
The new study on psilocybin showed that its longer term effects were due to immune system genes being turned on and off!
You have no idea how exciting that is! We can unwind it and pail and CBD are both tools there.
Premature ejaculation is multifaceted but there are some clues.
First, serotonin is a big player…in fact an inability to "finish" at all is a symptom of SSRI use.
Along with a loss of sex drive completely. Too much serotonin.
Low serotonin however may be something we can address and we know that CBD supports serotonin when low!
Then there's "performance anxiety" which is a self-referential thing with PE and many other kinds of "performance".
The public speaking study above is a great proxy for that aspect.
Test with higher amounts of 300-600mg about 1 hour before sexual activity.
If you hold under the tongue up to 60 seconds, effects can start in 10-15 minutes.
Check out the research on CBD and PE.
Don't worry…it doesn't taste bad which brings up a common question….
It depends on the product as some can be downright wheatgrassy (hemp oil base).
Our CBD isolate has just two ingredients:
If anything, there's a very slight coconut oil taste but you don't have the heavy cannabis taste or smell as you might with full spectrum CBD.
There are also capsules at 50mg with the same ingredients but no taste.
So…if there's a stressful situation coming which might cause anxiety, about 30
Minutes to an hour before ideally (based on public speaking study) is perfect.
Hold under the tongue if you just found out you have a presentation in 10 minutes!
You won't smell like Indonesia in the meeting.
Either way, no bad taste with CBD isolate and MCT oil. More on what CBD smells like.
Hyperactive immune response is basically inflammation.
It's directly tied to anxiety states and just about every mental health issue out there! There's a literal zoo of different players in this inflammatory response called cytokines.
The first piece:
https://www.sciencedirect.com/science/article/pii/S2666354620300107
Okay….and CBD's effect?
https://www.hindawi.com/journals/mi/2015/538670/
That's from a study on asthma (very inflammatory).
What gives with IL-10 which goes up?
It's actually a key player for lowering or "resolving" inflammation.
We have a massive review of CBD and neuroinflammation for anxiety with lots of research.
We have giant reviews on CBD versus benzos.
Benzo's directly boost GABA but there's a huge problem with this approach longer term.
The spikes are too high and the brain doesn't like this artificial interference. So you get tolerance.
The body will literally start to reduce the numbers and sensitivity of GABA receptors at the DNA level.
This means you have less and less natural GABA function and keep in mind, it's a powerhouse across the brain!
Literally, the "brake" pedal.
It also means that when the benzo wears off, your anxiety (or insomnia or pain, etc) will be worse than when you started.
Dopamine is also spiked so addiction follows pretty quickly but the standard warning is that 2 weeks of benzos is enough for tolerance and addiction to start ramping up quickly.
As we noted above, CBD supports GABA WHEN LOW!
So no tolerance, no addiction (dopamine doesn't spike), and no sedation trajectory like benzos.
Night and day! The black box warning on benzos should be a huge red flag but they're prescribed by the millions!
Check out how we used CBD to taper benzos if you're currently stuck there.
Big shocker…look at the results were why people continue to use CBD:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893882/
This really points to stress related issues!
Cortisol eats up GABA (and magnesium).
Serotonin is the stress response manager when GABA is under fire.
Anandamide is the ready-made backup when serotonin is calling for reinforcements!
CBD supports all three when low!
See:
Speaking of stress
Cortisol is our primary stress response messenger.
Let's go upstream to the chemical that causes the whole stress cascade (we're complicated machines!).
CRF - corticotrophin releasing factor
This is the trigger for the whole stress response system! The dam that breaks and eventually floods your body with anxiety if unchecked.
Does CBD have an effect all the way up the chain at the start?
https://pubmed.ncbi.nlm.nih.gov/30324842/
Now…that's not the coolest part of the study.
CBD did not have this effect when stress was low! Only high. It's really speaks to the beauty of CBD and the only reason we're writing 1000's of words on this article.
Different effects depending on the state of the system.
Cortisol (stress hormone) is not the enemy. We don't want to hammer it in one direction like other meds (benzos, barbituates, THC, etc)
In fact, it governs the wake cycle and you need it to get going in the morning not to mention when something urgent needs to be done.
CBD keeps it from running amok! And it starts all the way at the beginning with CRF.
Check out CBD and CRF to learn more.
It's helps to look at extremes to tease out how body pathways work.
Hello FAAH!
There are a few people on the planet that can't make FAAH due to a genetic mutation.
FAAH is the chemical that eats up anandamide, our "bliss" molecule from above.
THC mimics anandamide (but too long and too strong) and CBD supports it when low.
These people can literally not feel ANY pain. Or anxiety. Or depression.
The no pain part is why there are so few of them alive…it's very dangerous to feel zero pain on this planet.
They can have a broken one and not even realize it till they see it. How many times have you touched a hot stove??? See the issue?
But…what if we can dial down FAAH…let a little more anandamide back up stress response in terms of anxiety?
Till we can genetically alter FAAH with CRISPR, we'll have to rely on CBD for now.
Check out the study on woman who can't feel pain to learn more.
Yes. If the THC level is below .03%, it's officially called hemp and hemp-based CBD is legal in the US.
The FDA technically treats it as a food supplement.
Our THC level is zero since it builds tolerance with time and many people have nasty histamine responses to it.
Otherwise, our hemp is grown at USA farms (very important) that are FDA-registered (important) and with 3rd party testing (the most important).
Legal is just the beginning as there's lots of crap product out there unfortunately.
Learn about the legality of CBD or what make's up quality CBD.
So…what do large numbers of people respond back with regarding CBD?
A recent study included more people on the primary endpoints including CBD and anxiety late 2021:
https://www.businesswire.com/news/home/20211207005368/en/
So…anxiety, sleep, reduction in pain, and well-being.
Translation???
GABA, serotonin, and anandamide, reduced inflammation and stress response.
We're starting to repeat ourselves?
We have a massive review on medicinal mushrooms for anxiety and brain repair.
We've mentioned early trauma and infection above ad nauseum.
The "markup" from these primarily reside in the immune system.
After all, our immune system is a recorded history of what we (and our ancestors) have encountered.
Our distant cousins (fungi) have powerful effects in re-balancing our immune system when it's hyperactivated.
You can see the results in GABA, serotonin, BDNF, and the whole suite of inflammatory assassins called cytokines.
Don't believe us??
https://pubmed.ncbi.nlm.nih.gov/28008811/
Did you catch that? "Comparable to the standard drug - diazepam. You know….Valium, the benzo with nasty tolerance and addiction baggage.
L Lucidum is reishi by the way. Just one of many species with fascinating properties. We use this blend here (also check out CBD + Turkey Tail and cancer).
Check out the medicinal mushrooms as this is key to re-balancing our immune system longer term.
Haven't seen it in the research. In fact, we're not aware of a single overdose reported for CBD isolate.
Studies have tested up to 1500mg and even grams (1000's of mgs of CBD) with a strong safety profile.
If you've read this far, you'll know that CBD supports a system which is tasked with balancing other key systems.
It's not pushing key systems in one direction…working one level up.
You can overdose on benzos or other substances that push GABA up, up, up (barbituates, opioids, alcohol, etc).
Here's the trajectory of constantly pushing the nervous system "brake" pedal.
We're slowly reducing nervous system activity until eventually we just stop breathing.
Remember, GABA is the "brake" pedal.
With CBD, it supports GABA WHEN LOW.
Technically, called a postive allosteric modulator. See..
We don't see this nasty cascade of reduced nervous system activity with CBD.
Generally, the range of dosages runs from 50mg (very low) to 300mg for peak neurogenesis longer term.
More serious issues or points of high stress can go up to 600-800mg in research.
That's why we have a 6000 mg bottle. Each dropper is 200mg so that we can actually get to those levels shown in actual research.
We've danced around this area but it needs a better intro!
Oxidative stress is the increase of oxygen in various forms which occurs as a byproduct of how our cells make energy.
The so-called "free radicals". Oxygen is very destructive if left unchecked and researchers have known for some time that increased levels are intimately tied to mental health issues and anxiety specifically.
We're finally understanding why:
https://pubmed.ncbi.nlm.nih.gov/29742940/
The "machinery" of the brain runs on proteins and fats and they can get damaged by these little molecular scissors (oxygen).
Our primary detox agent is glutathione (more on glutathione and anxiety here).
We all know Vitamin C and Vitamin E are powerful anti-oxidants but guess what has them both beat??
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
Check out CBD and oxidative stress for anxiety or CBD and glutathione for more info.
NAC is a powerhouse here as well!
Phobia is all about "learned fear".
Apply to whatever you like but the process is the same in the brain and it's anxiety attached to a specific subject matter.
The key to phobias is the cue or context that triggers a cascade of anxiety and fear responses in you brain.
So…does CBD have any effect on this process?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121237/
Let's break that down…it's too cool!
Remember the whole BDNF pathway which is key to writing and overwriting learned pathways directly in the brain??
That's the key piece to dislodging phobias and learned fears.
Check out CBD and phobias for more info.
Pharma scrambled to find new options for anxiety since benzos were such a nightmare.
Enter the synthetic GABA agents.
Gabapentin and pregabalin being the big ones.
These are essentially synthetic versions of GABA since you can't really patent GABA itself.
So…have we learned anything about juicing up a powerful (maybe the most prevalent) neurotransmitter pathway in the brain as an agonist?
Hopefully. Tolerance is the enemy!
We see the same signatures:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988915/
Remember how the body will compensate for too much GABA activity by boosting its opposing force, glutamate?
We've looked in detail at how CBD does not cause tolerance because it's a "modulator" of GABA function.
It supports it when low so the body doesn't have to push back!
Learn more about CBD versus gabapentin and pregabalin.
If you use our under the tongue trick (with CBD isolate oil), it can start to work in about 10-15 minutes.
Pretty fast! That's the beauty of the sublingual gland right below the tongue…it's direct access to blood bioavailability.
Think of it as an early detection system for the body that we can hijack (in a friendly way) with CBD.
If we ingest it, the effects are generally 20-30 minutes…similar to say a Tylenol which also has to pass through the gut and liver.
Of course, CBD doesn't build up the toxic metabolite that Tylenol does in fact, there's research on CBD protecting the gut and liver for aspirin, NSAIDs, and more.
See CBD and gut protection or CBD versus NSAIDs.
Peak CBD is 4-6 hours after taking it
We spend so much time on the front office….neurotransmitters and brain areas.
The real magic with anxiety may be in the deep underworld of the autonomic nervous system functioning.
The "fight or flight" versus "rest and digest" systems.
Adrenaline runs the former and acetylcholine runs the latter.
That chest pounding, heart racing physical response?? YES…that system.
Anxiety is intimately tied to this balancing act and we can positively sway it in our favor.
We have a huge review of how to support the vagus nerve (seat of acetylcholine) which connects the gut and brain but what about CBD specifically.
So…CBD must have some impact there if anxiety is in play.
Yes:
https://pubmed.ncbi.nlm.nih.gov/32965166/
It also supported acetylcholine directly in the brain as part of the "wake" cycle which is why you can take CBD in the middle of the day.
Check out CBD and acetylcholine for more info.
Also, Choline CDP is a great support of this entire pathway.
We've covered above how important estrogen, progesterone, and testosterone are to our mental health, function, and anxiety specifically.
Take studies on estradiol (T is very similar since it's converted to estradiol by aromatase in the brain).
When they supplemented estradiol, it resulted in anti-anxiety and anti-depression effects to counter the results of losing their ovaries.
Guess what happens when they block endocannabinoid function (CB1) to this effect of estradiol:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169112/
The endocannabinoid (CB1 receptor) is key to estradiol's powerful effect on mood and resilience.
We know that estrogen drives serotonin and if you block CB1, serotonin loses its anti-depressant effects from above.
We also know that CBD supports this whole complex when exhausted (the anandamide support from above).
Check out estrogen and mental health.The pieces of the puzzle are coming together!
We already looked at CBD and public speaking for people with diagnosed social anxiety.
A study looked at CBD specifically for social anxiety in a double-blind, placebo controlled study at 400mg.
The results for people with diagnosed social anxiety:
https://pubmed.ncbi.nlm.nih.gov/20829306/
More interestingly, they looked deeper into how it was working. Scans were taken to look at changes in brain flow to different areas of the brain from CBD.
The results:
SAD is code for social anxiety disorder (FEAR & LOATHING didn't really work).
Ah ha! Limbic and paralimbic is part of our "reptilian" brain….the much older part tied to fear and basic responses.
Remember from the anxiety circuit above that these areas are too strong when compared to our "rational" brain - the prefrontal cortex.
We literally see blood flow activity change with CBD between brain areas!
We have a whole review on the top 10 tips for tapering here.
A few highlights.
Benzos build a brutal tolerance very quickly (about 2 weeks generally) which means your natural GABA function will be suppressed.
On top of this, benzos spike dopamine, the reward circuit behind addiction.
Between these two aspects, tapering benzos can be very difficult…right up there with opioids.
In fact, cold turkey is not advised depending on how much and how long you used benzos.
Glutamate gets ramped up as a push back and seizures are possible as a result with cold turkey.
Here's the highlight reel with CBD:
There are other supporting tools as well at our top 10 tip guide.
We saw the shift in activity from our "old" brain areas in the social anxiety example above.
Let's focus down directly on the amygdala, our center for emotional response including fear.
CBD appears to disrupt the "fear circuit" between the amygdala and other brain areas:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412699/
It also reduces stress from fear especially when we're outgunned.
A study on post traumatic stress disorder:
https://www.sciencedirect.com/science/article/pii/S2667242121000324
People…this IS the anxiety circuit. The key to the long term resolving of anxiety
Basically, CBD helps to re-balance the tug-of-war between our older "fear" centers (amygdala) and our calmer actor (prefrontal cortex).
So so so cool. Remember, if we're in a constant state of anxiety (amygdala is over powering), this get's wired in. It can also cause damage - depression!
Connections that fire together wire together in the brain.
People are so used to sleep aids and anti-anxiety meds that pound GABA that they expect CBD to do the same.
It doesn't. You don't see the sledgehammer effect like with alcohol, benzos, THC (cannabis), gabapentin, barbituates, etc.
CBD isolate does have a calming effect but it doesn't keep pushing beyond that.
Really, this is the beauty of CBD because too much of a good thing in the brain…is bad!
You also don't see the reduced cognitive function, brain fog, or speech issues like with these other players.
This "balanced" approach feels like…a stress response backup! For lack of a better word.
The removal of anxiety is not the same as the sledgehammer of feeling.
More on what CBD fells like.
It's the oldest anti-anxiety med out there (maybe cannabis gives a run for its money).
Alcohol is a very small molecule that literally makes the walls of our neurons more "porous".
Our neurons are made out of fats and the alcohol just thins them out.
This allows for free-form orgy of neurotransmitter activity!
We have a whole review on CBD versus alcohol but many people self-medicate to get this "rush" of feeling something.
The problem of course is tolerance and eventually…addiction.
You even have a temporary exhaustion of these powerful players and hences, the rebound feeling of "frazzled" or irritated or down. Hangover.
Basicall the mirror image of what you experience with alcohol. There's also a depletion of our detox pathway (glutathione) so everything's going to feel worse.
CBD doesn't have this "rebound" effect while still supporting the same key pathways. It also support glutathione and detox!
Learn more about CBD versus alcohol. You don't have the "euphoria" CBD like with alcohol (or cannabis) but you also don't have the payback!
No. Depending.
With clean CBD isolate, there's no risk of failing a drug test. Drug tests don't look for CBD levels since it's federally legal and treated like a food supplement.
So why the "depending"?
Legally, CBD can have up to .3% THC and THC will show on a drug test.
.3% is a small amount but it can build with time. Unless a product specifically states that it has zero THC (like this one), you can't be sure and use may cause you to fail drug tests.
Hemp oil also falls into the same category. Zero THC must be tested by a 3rd party and easy to find (3rd party testing here).
No. CBD is not an agonist, antagonist, or inhibitor.
It doesn't push key pathways in one direction which lies at the heart of how tolerance occurs.
The body/brain will push back the other way when an outside drug or supplement pushes in one direction.
It's actually very common and one reason we focus on key tools that avoid this trap. We don't want to actually get worse with time!
CBD is technically an allosteric positive modulator for key pathways (CB1 being the root one).
This means it supports activity when running low. Feedback mechanism.
A list or pathways here:
Learn all about how CBD supports the endocannabinoid system without tolerance.
Stress is a big player with anxiety. You can think of anxiety as a state when our stress reserve is exhausted. Makes sense…it's a tripwire that something is really wrong.
We've talked about our list of stress response buffers:
Pretty much in that order with mag and GABA operating simultaneously…the front line if you will.
CBD bolsters GABA directly when low.
Serotonin is the next in line:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704602/
When it gets exhausted, anandamide is called into action on demand (and broken down almost as quickly):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677118/
CBD directly supports anandamide when it's overrun by stress.
But without pushing it too far (like THC) which causes tolerance and reduction/rebound effects.
Tryptophan is also interesting as a stress response buffer - check out the review on tryptophan and stress.
Also, our full review on how to build resilience (some interesting tools there).
The general rule of thumb is at least 4 hours away from other meds but it's important to either work with your doctor/naturopath and check the contraindication checker here.
The key consideration is that roughly 60% of drugs and meds use a specific liver pathway which CBD also uses for metabolism.
If the liver is busy with CBD, it might allow other meds to stay in the system for longer periods, at higher concentrations, or not be metabolized into useful substances.
Up above, we use this "busy liver" trick to boost CBD's availability by taking it after food.
Same principle but with medications, it's important to work with a professional and check the contraindication checker.
More on CBD and other meds.
Read our new review on how to reset recorded "markups" in our immune system and epigenome from past trauma/infection.
Very modern research is teasing out how CBD affects this pathway:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917759/
DNMT is short from demethyltransferase…the tools that make edits to our control system of how genes turn on, how long, and when.
Anxiety reflects a dysregulation of genetic expression generally triggered from trauma, infection, or stress.
CBD normalizes this! At the epigenetic level!
Cutting edge 2022 research!
Let's peel back the curtain a bit.
Notice how you can't handle much when fighting a cold or flu?
We know from above that serotonin is a powerful stress response buffer but the ingredients for its production get thrown under a bus when we're sick.
Serotonin is made from tryptophan, a common amino acid we consume.
When we're fighting infection, the body will pummel the tryptophan pathway to starve out bacteria/viruses which also happen to use tryptophan to make more of themselves.
The downside to sharing basic building blocks with our attackers. The result?
Less serotonin which translates into:
Goodness…bad timing.
Now…what if our immune system is chronically fighting…inflammation?
See the issue longer term for anxiety and depression when the immune system is hyperactivated??
Bonus nugget…you need carbs to get trypophan across the blood/brain barrier.
Every wonder why you want the donut and starchy badness when feeling sick? It also competes with other proteins for access to the brain.
Check out the tryptophan and inflammation connection.
If you thought tapering off of benzos was bad, wait till you see SSRIs.
Technicaly, it's called serotonin discontinuation syndrome but we have a different word for it.
Absolute hell!
Big review on tapering off SSRIs here but a few key takeaways.
Serotonin manages all human behavior…it's your "feel right in your skin" player for lack of a better word.
Since SSRIs build tolerance, you're flying without a net when tapering. It literally feels like you're coming out of your skin.
The number and sensititivy of serotonin receptors literally gets ramped down longer term.
We had to go very slow over 30 days with lots of support.
Work with your naturopath/doctor (hopefully not the one who prescribed them after a 10 minute consult).
CBD supports serotonin when low (the injury study above) plus there are other key tools to give you a fighting chance at our top 10 guide.
Just remember that the real star being serotonin is BDNF, our repair pathway, and the key is giving it a break from stress, inflammation, etc.
We've looked many times at how CBD can have different results depending on the state of our system. Even different areas of the brain!
The study on CBD's effect on GABA (key to anxiety) for people with autism is very instructive of this!
First, the results:
https://pubmed.ncbi.nlm.nih.gov/30758329/
So…basically, CBD boosted GABA in the control group but lowered it in people with autism specially in the prefrontal cortex.
Remember that GABA slows activity generally. People with autism generally have less activity in the pre-frontal cortex (our rational, thinking player) and CBD actually reduced GABA there!!
This reminds us of the dopamine effects in different brain areas for schizophrenia….raising it where low (pre-frontal cortex) and lowering where too high (striatum).
Why bring this up??
Our brain and its messengers are incredibly complicated. GABA alone can such disparate effects depending on where it operates and in what state.
CBD's nuanced effects are very powerful compared to say benzos which just spike GABA everywhere (so your thinking becomes sluggish, etc).
A perfect example of why we get so excited about CBD for anxiety which has a big GABA component.
Check out the review on autism anxiety for more info.
Great question. Quick answer. No!
CBD by itself does not have a feeling of euphoria or "high".
The "high" from THC (cannabis) is from mimicking anandamide, our "bliss" molecule.
CBD supports anandamide but when running low by interfering with FAAH…the substance that readily breaks down anandamide.
Since it doesn't drive anandamide up up and away…we don't get the high...or the tolerance!
Think of anandamide as just keeping you high enough! Feeling pretty good.
Euphoria is what happens when you push this pathway past the natural limits. The downside to this is that you exhaust it and with longer term stimulation, cause tolerance.
Actually less numbers and sensitivty for CB1 receptors where anandamide plugs in.
We don't want to whittle away our bliss molecule and a key anxiety push back buffer, do we?
Sorry…no "high" then. Learn how CBD can protect the brain from cannabis and THC.
PPAR is a fascinating pathway. A key manager of inflammation in the body and brain.
For anxiety, it's all about stress response:
https://www.frontiersin.org/articles/10.3389/fphar.2018.00998/full
PPAR is actually part of the endocannabinoid system that CBD works in so…what is CBD's effect on this stress response buffer?
https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13497
Let's translate.
When the block PPAR, CBD and other endocannabinoids lose some of their activity.
PPAR is key to how CBD helps with anxiety, inflammation, and a range of issues.
Just one more avenue on how it works for anxiety.
There's a lot of hype about hemp oil out there in the market. Basically, they're piggybacking the research (like above) on CBD.
We're not anti-hemp oil but let's be clear…it's like buying very expensive olive oil (similarly healthy Omega 3/6 makeup - see the role of fats in our mental health).
We enquired with a HUGE hemp oil brand into how much CBD they had in their product and they couldn't say!
In fact, many have about 80mgs for the whole bottle that might retail at $60.
Our 1000mg bottle is the same price. See the problem?
With research pointing to levels from 300mg for peak neurogenesis (the repair side), you'll never get there with hemp oil.
Then there's the whole histamine issue we've discussed above. The whole reason CBD isolate has such a better response for 40-60% of the population is the removal of plant material like you find in hemp oil.
Learn more about hemp oil versus CBD isolate.
GRRRRR. If we see this one more time.
Talk to anyone casually in the business and they'll parrot the statement "you need THC to activate CBD".
The whole "entourage effect" slogan.
Turns out that term was coined to reflect how CBD would COUNTER the negatives of THC by the Godfather of CBD research.
THC can actually cause anxiety in some people (the histamine aspect) and the two have very different responses in the body since THC pushes CB1 activity (where anandamide works) in one direction but for too long and too strong.
If anything, CBD "buffers" THC. We did a deep dive on why CBD is a must if you use cannabis.
The issues of course is that THC builds tolerance which means our natural anandamide function drops with time. That's the wrong direction to go!
Learn all about the THC activating CBD ruse.
Three key aspects to getting the most out of CBD and all the research you read above (you poor soul!
First, we have to make sure it's a good product.
The basics:
Those are the basic requirements and our third party testing is available here or at the top of ANY page.
There's lots of bad product out there so be careful. No third party testing of ALL the elements above is a deal-breaker.
Type of CBD
We've covered the full spectrum versus CBD isolate question for anxiety.
99% of the research is on CBD isolate (CBD by itself).
More importantly, histamine is such a big player, and the side effect profile between isolate and full spectrum are SO different. Just look at the product reviews.
Since hyperactive immune response is a big player with anxiety, histamine is probably an issue if you have anxiety. They go hand in hand.
CBD isolate actually calms this inflammatory response! Learn more about CBD, histamine and anxiety
Then, there's cost.
With peak neurogenesis (the long-term star for anxiety) at 300mg daily in research, cost per mg of CBD becomes key.
Huge differences out there on the market!
We price the 6000mg bottle at 2-3 cents per mg before discounts up to 50% since we've been there (rolling anxiety).
No. Studies have shown that CBD doesn't spike dopamine, our primary reward circuit for addiction.
In fact, studies such as the one on schizophrenia shows that CBD can balance dopamine differently in separate parts of the brain!
There's a ton of research on CBD for addiction itself as well as the withdrawals driven by tolerance.
Outside of psilocybin, CBD is probably one of the most promising tools for addiction.
As for CBD itself, it doesn't spike dopamine or build tolerance since it supports the system that balances other systems. Think of addiction as an imbalance (in the reward circuit).
Compare that with benzos (primary med for anxiety). Black box warning and brutal addiction there.
We've covered the main brain areas tied to the anxiety ciricuit.
Let's look at the communication links around the brain which can directly affect anxiety.
White matter is directly tied to anxiety states…especially trait or long term anxiety:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117387/
Remember how we said that CBD is not the same thing as THC?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150138/
Brain highways. White matter! One more issue with THC.
A study looked at 18-19 year old Japanese students with social anxiety disorder diagnosis for two important tests of social anxiety.
The results:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856203/
What is the dose? 300mg of course (remember, that's peak neurogenesis from above longer term as well).
If you have a stressful or social situation come up, 300mg about 30-40 minutes prior matches the research.
Longer term, 300mg daily works on changing long term brain pathways tied to anxiety.
Check out CBD and social anxiety or our review on self-esteem
We looked at how oxidative stress can directly feed the anxiety monster in the brain.
Glutathione is our primary detox (now you know where the "ox" comes from) in the body and brain.
They can literally see on a sliding scale the reflection of anxiety states by glutathione metabolites in urine:
https://www.hindawi.com/journals/omcl/2014/430216/
What about CBD and glutathione?
Thought you would never ask..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
Peroxidase and reductase are powerful weapons in the detox pathway.
MDA is a highly toxic substance reflecting we're losing the oxidation battle.
We mentioned above…CBD is actually much more potent as a anti-oxidant than either Vitamin C or E.
One note in the above… "in inflammatory conditions". This is critical.
The body uses oxidative stress to kill off cancerous or virally infected cells.
CBD is one of the few substances that will calm inflammation when too high but actually increase it in faulty cells! Check out CBD and cancer to learn more.
As for anxiety, hopefully we've established above that it is definitely an "inflammatory condition" in the brain!
Needless to say, we have an anxiety epidemic right now with young people and very poor tools (benzos and SSRIs).
An Australian study looked at CBD for people age 12-25 with anxiety and found the following:
https://pubmed.ncbi.nlm.nih.gov/35921510/
Similar results were found for depression which isn't suprising once you understand the inflammatory nature of both (everything above).
Exciting and we need more studies but expect more of the same. THC is a no-go under the age of 25! Can actually lead to increased future anxiety/depression risk.
Here's a weird one. Benzos, the biggest class of anti-anxiety meds pump up GABA (and tolerance/addiction).
Meanwhile, they're giving the complete opposite signal to our brain waves which reflect system-wide communications:
https://pubmed.ncbi.nlm.nih.gov/15223295/
Beta activity means - high alert! Danger!
While they're telling your brain to relax, they're telling your nervous system to panic!
Very strange and we did a full review of this benzo brain wave effect.
Strike 32??
Big review on top 10 tips to get off benzos but just the headlines:
It's the new Opioid crisis in the making!
More detail on each benzo taper tip.
Many people assume CBD feels like its cousin, THC.
Totally different and this also goes for motivation and focus.
THC works like a big wet blanket in the nervous system so it can definitely affect motivation.
In fact, we looked at whether this is why some people use cannabis daily.
CBD can actually give energy/focus during wake cycles.
This is partially by driving acetylcholine, our "calm and focus" manager (you'll want to get to know it if dealing with anxiety).
In the public speaking test, there was no impact on cognition, verbal/physical execution, or motivation. At 600mg!
It's just not part of how CBD works in the nervous system. We all know that anxiety is not the opposite of lazy…it's the opposite of calm!
Learn more about whether CBD will make you lazy.
Let's say you have a stressful situation coming up.
A date. A job interview. Intimate first with a parter! Just life!
You can take 300-600mg of CBD about 40 minutes prior to the event based on research.
This timeframe can be reduced by holding the CBD under your tongue up to 60 seconds.
Then, we're looking at 10-15 minutes due to the sublingal gland being directly tied to the bloodstream.
The tongue trick is great no matter what to boost bioavailability but it can also speed the anti-anxiety effects of CBD when needed.
This also works after the fact…say, when you just had a very stressful event like a car accident or a fight with a friend.
It's about re-balancing our various pathways from GABA/glutamate (excitability) to fight-or-flight/rest-and-digest (autonomic nervous system).
Our stress response buffers get exhausted in this order:
CBD supports all of these (sans magnesium so 300-400mg magnesium glycinate daily is great when under stress or as needed).
Tryptophan may also be a good support for stress response (the main ingredient for serotonin) but away from other protein.
More on tryptophan for stress or CBD for stress response.
Remember, anxiety is just stress run amok in terms of our basic hardware.
No. We did a deep dive on CBD and blood tests.
Many people are curious if it will "show" on a blood test and it doesn't.
Drug tests don't look for CBD.
As for your core blood panel work, CBD also doesn't alter the basic metrics they look at.
There can be positive effects (blood pressure, liver function, etc) with clean CBD isolate (can't speak for full spectrum) but it's pretty minor unless a person has significant issues.
For example, if your glutathione (detox pathway) is exhausted…say from chronic alchohol use, CBD may actually help there.
Otherwise, CBD doesn't not impact your standard blood test results.
No. CBD is treated like a food supplement by the FDA when it meets the less than .3% THC requirement.
That being said, we want ZERO THC for anyone with a developing brain (up to age 25 ideally).
There's pretty compelling research on THC having impacts on the developing brain (white matter, etc) and even possible risk for anxiety.
Studies show how CBD can actually counter this damage which is why it's so essential for people that use cannabis but again, no THC is critical for developing brains.
We have reviews on CBD and child anxiety or CBD and teen anxiety with lots of research.
Steroid hormone flux is a huge source of anxiety (say during puberty or perimenopause) so CBD comes up often during this time.
Also, trauma, early-life stress, and infection can hyperactivate the immune system which directly increases anxiety risk (as well as every mental health issue).
Calming this response is right in the wheelhouse of CBD (see CBD and neuroinflammation).
The whole PANDA issue (strep throat and OCD/tics in children) example is a powerful one.
The immune system responds to early infection about the same as early trauma. Act accordingly. Learn more about CBD and immune system review.
We covered why THC, longer term, is in the wrong direction since it builds tolerance.
Also, we looked at how THC doesn't "activate" CBD…in fact, they oppose each other in many pathways.
So…what about the often questioned "ratio".
You know our answer (zero to 100%) but let's be more nuanced.
IF a person wants THC in the mix, ideally, have a 1:1 ratio at least (more CBD, the better) to keep the excesses of THC under wraps.
Again, that was the original meaning of the "entourage effect".
THC should be less psychoactive with CBD as a counter. In fact, CBD (and pregnenolone) can help for THC excess (see CBD for greening out).
There are still downsides to long term THC but at least have CBD as a counter. For example, you can use the 1000mg bottle dropper after/with cannabis use as a buffer.
Look..just looking at how THC disrupts our mitochondria (all energy production) or sleep architecture is reason enough. Both are intimately tied to anxiety!
Learn more about the CBD/THC ratio for anxiety.
This is a horrible story. Significant abuse at an early age. Medications were not working.
CBD's effect:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101100/
Remember…early abuse, stress, and infection can upset the entire apple cart in our brain (see the very last blurb below).
This is the key to long term healing! Also, you can't fix anxiety without fixing sleep first!
Check out our CBD and sleep review or CBD versus ambien
Net net..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763649
More on sleep below.
We've tried it all! You name the supplement and it's somewhere in our pantry from the bad old days of rolling anxiety and panic attacks (that story is here).
There's lots of supplements that get glowing reviews online but can actually not feel great.
They fall into a few categories:
If they work for you, great. Here's the rub…
Some of these can build tolerance where you body will actually push back over time.
The body really doesn't like tinkering directly with key pathways like serotonin and GABA.
Tolerance is the enemy….that's why we only focus on tools that build tolerance like:
L-theanine (green tea extract) is billed as a calming agent but it can actually make you feel janky if you're body responds in kind with histamine.
Just a head's up…there are few substances that support key calming pathways WITHOUT tolerance and/or histamine.
The above toolkit are the key ones.
Anxiety tied to autism is a known source of distress for both the person and their loved ones.
Autism definitely shows powerful signs of early trauma/infection/stress (especially in utero) so all the usual suspects abound.
CBD's effects there:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675523/
Most importantly, longer term use (2 years plus) resulted in improvements in cognition! That's the OPPOSITE of tolerance. See can you use CBD long term.
Remember, we don't want to use tools that build tolerance and lose effects over time.
There's a big review of many studies surrounding autism anxiety and more here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563787/
Brain scans of people with sleep loss look just like…significant anxiety!
This isn't too surprising to anyone with a bad night of sleep.
Many of the same pathways are are at play with sleep and anxiety:
We have a huge review of CBD and sleep but a big study shows the cross-over:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/
CBD was well tolerated.
Many more studies at the link above.
We've seen multiple studies on children and teens above but let's recap.
The primary concern with any medication or supplement for children revolves around the following:
We've addressed the latter.
What about development?
Most of this data came from childhood epilepsy and keep in mind, that the side effect profile of synthetic cannabinoids is much different than pure CBD isolate.
The side effects from Epeliodex and other synthetics is night and day from pure CBD isolate (assuming good quality and 3rd party tested).
We don't have hard research on long term safety for children but we do know that CBD works like a feedback mechanism. Overdose would be an issue if not and we don't see that at very high levels.
The alternatives (benzos, SSRIs, anti-psychotics, etc) carry much higher burdens (tolerance being the gorilla in the room).
We look forward to further research and if we come across a study that shows negative effects on development, we'll add it.
As for steroidal hormones (big players in development), CBD isolate does not directly affect estrogen, progesterone, or testosterone (publishing soon - search here) in research.
We have reviews on each.
Check out CBD and child anxiety or CBD and teen anxiety for more detail. The tool kit above is also critical!
Remember, states of hormone flux (hello puberty!) are primary drivers of anxiety as we learned the hard way during a brutal perimenpapusel
Back to the reptilian brain. The memory and mood switching hub.
Because of it's role in forming memory, the hippocampus is very vulnerable to all the insults we've discussed (stress, infection, drugs, inflammation, etc).
It's also one of the few sites of significant growth/repair (BDNF) which we can take advantage of!
Mindful meditation and exercise both drive this. As does CBD!!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908414/
Okay…lets' break that down.
CBD drives more connectedness and in the all powerful hippocampus.
This drives its….anti-anxiety (anxiolytic) effects! Also…this is from prolonged use!
Prolonged benzo use will land you somewhere quite different.
Learn more on how to support hippocampus neurogenesis.
A lot has to go right for our brains to work correctly.
For clear thought (opposite of brain fog), we need the following:
That's just the start but a good one at that.
So…we saw from the public speaking study that CBD did not impact cognitive or verbal function during peak stress. Can't say that for THC, alcohol, or benzos.
CBD appears to help with cognition in times of stress or impairment:
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00034-0
Notice the THC note! THC longer term is not great for brain function. Too much of a good thing essentially.
CBD is just enough of a good thing…when needed (called alosteric positive modulator).
Remember that in people who were just on the cusp of psychosis…
Goodness. Check out CBD and psychosis.
Extreme anxiety is very similar to psychosis in terms of cognitive function…the thinking part (prefrontal cortex) is overrun (think..."freeze up") by the fear/emotional center (amygdala).
Estrogen and testosterone both drive serotonin. Progesterone drives GABA.
Outside of early trauma/infection, steroid drop is probably the biggest driver of anxiety (just look at the monthly cycle or perimenopause).
The last thing we want to do is monkey with these powerful players of mental health (see estrogen and mental health) as an example.
Does CBD affect them?
No. Even though the endocannabinoid system manages our steroidal hormone complex, CBD itself does not directly affect their levels.
Remember, CBD is a balancing feedback agent.
Unlike THC!
THC will suppress steroidal hormone function…again, it's a big wet blanket across the body (and ovaries/testes).
Get your steroid levels tested and learn about bioidentical hormones if low.
Can't stress how important these pathways are to anxiety and health in general. Learn more about steroids and longevity.
There's a mad rush to push other cannabinoids as magical things.
Delta8 is the new entry to this effort.
Look…we could easily offer options with any/all of these since they're all legal (Delta8…maybe not for long..it's basically discount THC).
The reason we don't is that they are mainly agonists. That's the technical term for pushing pathways in one direction.
When you do that longer term…the body strikes back (is it the Empire??).
We want postive or negative modulators. Feedback support when a pathway is too high or too low.
You can't monkey with serotonin in one direction, the manager of ALL human behavior and expect good things. Che
Too much serotonin (called serotonin syndrome) is even worse than too little. Trust us…worst few days in our founder's life!
Here's a look at how the cannabinoids work.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/
We want modulators. Not agonists/antagonists/inhibitors.
This is the way back to health and away from anxiety longer term.
We're in this to win it!
Let's go real obscure just to show off our chops before wrapping up with the most important take-away.
Sometimes called the "third cannabinoid receptor", GPR55 is fascinating and CBD is in love with it!
Scientists can trigger anxiety just by blocking it in certain parts of the brain tied to panic and anxiety.
Here's the interesting piece…
There's a gender difference in how GPR55 is expressed and where.
Women get hit by anxiety at a higher clip than men and GPR55 may be part of the puzzle.
Also, early life stress (we repeat ourselves) directly affects this pathway's function.
Learn all about GPR55 but CBD directly supports its activity…when low!
If your anxiety is just situational…say from a specific event, okay. CBD can help there as needed.
However, if anxiety is more established or long term (trait or general anxiety, etc), then we need to talk.
Outside of pretty extreme, genetic variations (which the body usually finds works around for), there are two big culprits in the newer research:
Steroid loss is how we found CBD to begin with…a brutal perimenopause when estrogen went on a roller coaster ride.
Testosterone drops 1% each year from around age 20
So…get your levels tested. Support when needed with bioidentical hormones (no synthetics…NIH studies show the downsides even if your doctor poo poos it).
Hormones are dropping across age bands these days due to the various chemicals we come in contact with (sunscreens, estrogens in food, etc).
The drop in average testosterone over the last 20 years is frightening!
Test…and support.
The other piece is more fascinating! And actionable!
A study looked at the longer effects of psilocybin (which is going to revolutionize mental health).
It turns out the LONG TERM effects were driven by genes being turned on/off…in the IMMUNE SYSTEM!
Think about that…why does the immune system drive anxiety and just about every mental health issue out there (yes…every)?
Let's introduce the epigenome…a set of instructions on what genes are turned on, how much, and for how long.
Picture the EQ board for stereo (bass goes up, mid goes down, GABA goes down???)
It's also a kind of adjustable history of how the body has interacted with the environment.
It turns out that early stress/trauma/infection can hyperactivate the immune system and cause a range off life-long changes such as:
Goodness. Can we drop the mic now!
Descendents of Holocaust survivors show increased risk of mental health and even changes to metabolism.
You have to "unwind" this effect to really address anxiety and mental health.
We all know PTSD which is a sudden "rewrite" or hard edit to immune response but we're all walking around with some epigenetic baggage (maybe our parents…they're nuts!!).
Remodeling our immune response is critical and we have tools for this:
Yes, we want to feel less anxiety now (CBD and mag) but we also want to become more "resilient" longer-term (CBD, mushrooms, steroidal hormones, vitamin d, NAC, etc)
Steroidal hormones and epigenetic editing via the immune system is how we do this. Big review here or here.
It's the future of mental health (but now!!!!). There's never been a more exciting time to have anxiety. And squash it!
Use FIRST50 code to test below. We'll cover half because...well..the research is on our side.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
Let's just call it the Five Horsemen of the Medical Establishment Apocalypse...
Clippity Clop. Clippity Clop.
You can hear beating hoofs just around the bend.
Our introduction to the current state of medicine - treatment for anxiety as an example, was poor at best. The current status is woefully flawed and reflects 60 years of stagnation.
Actually, the new additions (Xanax and Ativan) are much more addictive and problematic (see benzo review).
Big advances are ahead in how we view and treat health with CRISPR and Yamanaka factor work coming online.
We'll get into those below but till then, there are pretty amazing tools available….right now!
Tools that have powerful effects on every pathway of your body and brain for the better. General longevity and health!
In this case, it's five horsemen!:
If I had to choose 5 supplements to take to a desert island (Vitamin D is covered with the sun, right??), it would be these fivw currently.
We'll get into why below along these topics:
It's an exciting time to take back your health and this is at the top of the list of tools.
Pharma and traditional medicine's time is coming due! Queue the hooves.
Okay…these 5 players…why did they make the list?
First, some requirements.
CRISPR promises to revolutionize medicine but Yamanaka factor research is even more exciting.
We have a whole review on Yamanaka for longevity but the quick skinny.
Our DNA is a hard set of instructions to make/run each of our cells. It doesn't change much.
That's nature.
Our epigenome sits right on top (figuratively) and determines how, when, which of those genes get turned on.
Our interaction (and our parents and their parents…etc) directly change this layer.
Little "mark-ups" to this layer also accumulate as we age which drives…aging!
We did a huge review on editing our past's health code.
Yamanaka research (attracting billions of as we speak) aims to strip these mark-ups away which is showing powerful effects to make bodies/brains appear more youthful!
Like we said…exciting stuff. Till that's ready (almost all disease is tied to aging), we need some interim players for longevity and health.
That's this list! We have 1 million+ words of research across many pathways and 1000's of hours buried in NIH research.
These players are the most exciting!
Let's get into it.
Originally billed as an anti-fungal, rap has the best track record for longevity gains.
This is reflected by the ITP (Interventions Testing Program - the gold star of longevity testing) and countless studies across multiple species from yeast to humans!
ITP's result:
https://www.nia.nih.gov/research/dab/interventions-testing-program-itp
So…what is rap?
Essentially, it blocks a pathway called mTOR which functions as a nutrient (protein) sensor in the body.
A quick intro is needed…
All living things (that scientists have looked at) have this system in place in case of hardship.
Famine. Drought. Heat. Cold. Bad times to reproduce essentially.
mTOR runs hot during good times and slows down during bad times which throws the body from growth..to housekeeping.
The net effect? Huge changes in just about every metric of aging and health.
Too much to go into here but there's a great hub here:
The current approach till we have more guidance is the following:
One note…rap is known as an organ rejection drug but that's at higher levels/daily. Forever!
The pulsing option (once per week with washout) has actually been shown to improve immune response!
Check out the link above. You can go to pushhealth.com and request it with the reason being "longevity". GoodRx offers discounts if your insurance doesn't cover it.
There's fascinating studies on topical applications as well.
We take one 2mg tablet and dissolve the outer shell. We then place the rap without the coating in a 2000mg CBD bottle and use topically with microneedle device.
A study with rap and ECGC (green tea extract) showed interesting results for regrowing hair and microneedle device (which boosts absorption).
I'm currently in the washout period…and I'm missing how Rap feels! One more week to go. Very exciting tool across just about many metric you want to look at:
Rap is front and center.
A few key notes:
Rap can suppress steroidal hormones and you know how dearly we view them (see steroids and longevity).
For this reason, we're actually switching to 2mg one week and then a week off. Run your labs (metabolic, lipid, steriodal hormones, etc) and adjust accordingly.
Next up, closest to our heart.
Sure…we're partial here. After all, CBD isolate helped up navigate a brutal perimenopause.
For good reason. CBD isolate is a gift down here for health.
We have 100's of reviews across almost any category you want to look at but a quick intro into why it's so fascinating.
Every living animal has an endocannabinoid system…it dates back about 600 million years evolutionarily speaking.
This system is tasked with balancing just about every other system after stress including:
We use the word "stress" generally…meaning anything that pushes a key system in one direction or another.
For example…you have a date.
After the date (or hopefully before it ends), this whole "crap, we're on a date" cascade needs to return to normal.
You can't stay in that state forever or you'll burn out.
In fact, constant stress…becomes anxiety! Essentially, our stress response buffers (serotonin, GABA, anandamide) exhaust.
CBD supports this balancing system when it's outgunned!
Unlike its cousin THC, it doesn't push in one direction (hence the side effects and tolerance with THC). It supports when low!
A feedback mechanism. Technically, a positive allosteric modulator.
It's a beautiful thing because very few supplements/medications we have work this way.
They usually push key pathways in one direction and tolerance/side effects result.
In today's world…balance is sorely in need!
To learn more, check out:
The last one is all about the epigenetic markups we discussed above.
The trauma one is even more exciting. Remember the "markups" to our epigenetic layer?
Trauma, infection, and early stress also brings out the red pen! CBD and psilocybin are powerful tools to erase these edits.
We take 300mg daily (this one) which matches research on peak neurogenesis (brain repair/replenishment).
Next up…to the gut!
We're slowly learning that metabolism IS health. Especially on the longevity front.
Remember how mTOR's primary signal to ramp up is insulin? Glucose is an Enemy of the State (the state being our body).
We did a deep dive on the problem with glucose.
Akkermansia is an example of a gut bacteria strain that has powerful effects on:
Wait what??? Why mental health?
The gut is our "second" brain with the 2nd biggest number of neurons behind the skull.
They communicate together directly through the vagus nerve (more here - get to know it!).
Akkermansia is partially why metformin and berberine show their powerful effects across the body.
Gut inflammation states directly drive:
Check out our reviews to learn more:
Pendulum has a great akkermansia supplement or their Glucose Control which combines akkermansia and other butyrate forming bacteria.
We lost 10 pounds after starting glucose control. The gut microbiome IS part of the future of better health.
Check out probiotic review to learn more.
Next…to the brain (via the immune system)!
Big review on Psiloycbyin since it's going to revolutionize mental health shortly.
The primary substance of magic mushrooms, psilocybin is showing impressive results across almost every facet of mental health and addiction (intimately tied).
It's an explosion of BDNF, our brain's repair/growth factor plus a reset of the connectome…how our brain is integrated system wide.
When you dig down into any substance that is used for mental health (CBD, SSRIs, Exercise, Mindful Meditation, etc), you find this pathway!
It doesn't have to be a full trip. The future for people over a certain age will be about maintenance doses (.1-.5 grams) to keep the brain more "plastic".
This is basically a cheat code to function in a more youthful state when BDNF is flowing (the reason you can learn a language so much earlier when young).
Yes…we all have it and it may go back to in utero or even past generations (up to 10 in studies).
Do we have a clear explanation of how our past affects our present and the key pathway?
The immune system records the damage.
Here's the fascinating part with psilocybin or medicinal mushrooms in general.
A study found that the long term effects of psilocybin were due to genes being turned on and off…related to the brain's immune system!
Yes…rebalancing immune function drove the positive benefits long term.
Learn why the immune system is the future of mental health or better yet, read our simple summary review.
Finally….the workhorses of the body and brain.
We need a whole rethink on estrogen, progesterone, and testosterone.
So much misinformation.
This has nothing to do with reproduction, libido, or muscles (even though they directly benefit).
Every cell in your body has receptors!
So how to view them?
Let's take one example (of thousands)
Serotonin. Our master regulator of ALL human behavior. It's not the "feel good" neurotransmitter.
More like feel "right". Right in your own skin player.
It also drives BDNF, the brain's fertilizer from above with psilocybin.
Here's the rub:
The research on supplementation is just ridiculous. Dr. Attia's rewind podcast gives a good review.
You can almost pick any issue and find a positive impact.
So why aren't we all on it? Why hasn't you're doctor been prescribing instead of drugs to address the symptoms of its loss (SSRIs, benzos, sleep aids, blood pressure, statins, etc)?
A bogus WHI study in 2001-2002 scared everyone off of estradiol (big review here)
Similar hit pieces in 2013-2014 did the same for testosterone.
It gets worse. These were primarily based on synthetics which do not function the same as bioidentical (just look at NIH studies).
For example, the new Bijuva (bioidentical oral estradiol and progesterone) actually showed BETTER profiles for ovarian cancer and blood clots (the two boogeymen from 2001 study).
Read the research!
Make sure it's bioidentical.
Estrace for estradiol and prometrium for progesterone.
We had to get a sublingual testosterone from a compounding formulary since the creams don't absorb well.
The Dutch test is a great way to see your results and don't take the "your numbers are fine for your age" nonsense.
Does 50 feel like 25?
Related Research:
Okay…some honorable mentions.
If we were allowed a bigger bag on the desert island, we'd bring the following:
Big reviews for each of those.
Finally, we have a giant guide on cold exposure and mental health in the works. Goodness...it's a monster hack down here!
Otherwise, the big 5 are as close today as we have to bridge over to Yamanaka factor options and CRISPR…the next revolution of health care.
And they're available RIGHT NOW!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
Learn how the great switch from omega 3 to omega 6 heavy seed oils have ruined health for a generation
]]>We're going to start this review with a few visuals to get the ball rolling.
https://www.nature.com/articles/s41599-018-0201-x
This is interesting on a few levels.
The obesity hockey stick is what we want to focus on. Right around the '70s-'80s period.
We can also see that sugar predates this explosion by decades. HFCS's (high fructose corn syrup) drop around 2000 but doesn't really dent the obesity rise.
We already covered the damage with glucose but there's another fascinating player.
Fats. The kind of fats specifically.
Take a look at this and see if it's a closer fit to the obesity epidemic:
https://www.researchgate.net/figure/Annual-added-fats-and-oils-availability-per-capita-from-1909-to-2019-Source-USDA-ERS_fig5_357837179
Any connection with obesity?
https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/obesity-adult.htm
Look at the green line. Up up and away.
What about diabetes prevalence?
Okay…uncle.
Alright…roll up the sleeves…we're going deep to see if the massive switch to why seed oils is at the root of many ills.
Wait till you see the effects on appetite and dopamine (addiction) below! You're going to be hungry…for revenge!
We'll cover the following topics:
Let's look at the biggest con game in food and health…maybe ever!
One year ago, I had no idea how critical this was to health.
Like a good majority of the population.
We've been bashed over the head for decades now that fat is fat and it's all bad for you.
Our bodies have immediate uses for protein…and fat. Protein runs the machinery of the body while fat provides the architecture and scaffolding of our cells.
Sugar and carbs (just a more complicated version of sugar) are not directly needed as is evident from keto. Our body can convert protein into glucose to power its activity.
Fat, however, is essential. Steroidal hormones are derived solely from…LDL cholesterol. Yes…the so-called "bad" cholesterol.
The literal walls of your cells are made from fat. Your brain is approximately 75%...cholesterol!
But not all fat is equal!
A quick history.
As you can see from the chart above, our primary source of fat for…ever, was animal fat. Butter. Lard. Tallow. Etc. Sure…some coconut, etc depending on where in the world you were cooking.
Two brilliant marketers realized they could take industrial oil (cottonseed oil) and add flavor plus color. Voila! A ridiculously cheap form of cooking oil!
You're witnessing the explosion of Proctor and Gamble as an economic powerhouse.
There's a great run-down at this link but the takeaway:
https://www.theatlantic.com/health/archive/2012/04/how-vegetable-oils-replaced-animal-fats-in-the-american-diet/256155/
The processing of seed oil to cooking oil is a nasty process with solvents and chemical extractions.
It's factory food. Plain and simple.
As you can see above, it exploded in terms of share of fat calories around 1965 and the marketing prowess of Crisco sits front and center with this growth.
It never looked back.
Julia Childs once said she would never eat McDonald's french fries (she was a fan) again after replacing lard with vegetable oil.
The tide was never going to turn…cost of this factory oil was just ridiculously lower than animal based fats.
Take a look at almost any packaged/processed food. Seed oils are there.
Sunflower. Safflower. Rapeseed. Canola. Vegetable.
We'll ignore that most of the seed is raised with glyphosate, pesticides, GMO, and a brutal chemical extraction process.
Let's turn to the chemistry of the fat at the heart of this massive transition.
There's a great intro to the whole sordid history here:
https://drjasonfung.medium.com/the-shocking-origin-of-vegetable-oil-garbage-1c2ce14ae513
The charts will start to make more sense.
Fat actually has different forms and makeup with the basic categories being:
The unsaturated fats are broken into monounsaturated and polyunsaturated fats (PUFA)
Trans fats are cooked in the presence of hydrogen essentially to keep them from breaking down (spoiling).
The only thing everyone agrees on with fats is that trans fat is the Devil! (to quote Waterboy).
The other items are open for debate, unfortunately.
Saturated fats (animal fat essentially) have been the target of ire and derision for decades now but research is flipping on this.
The much supported PUFAs are actually not so great.
A pretty good explanation of the fats can be found here:
https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/
The whole keto movement has obliterated much of what you'll read there and it's clear that glucose, inflammation, and processed food is really where the focus should be.
There's so much confusion on fats and a great deal of this comes from cholesterol.
As we mentioned, cholesterol is the root ingredient for all steroidal hormones and they directly drive every pathway in the body including….cardiovascular health!
We learned that the hard way from a brutal perimenopause (see perimenopause cardiovascular when estrogen leaves the scene).
Let's take one example.
Coconut oil.
If you go by the basic guidelines, coconut oil should be a veritable poison. Loaded with saturated fats.
A study on people who exclusively use coconut oil (fruit oil along with avocado and olive) found they have higher cholesterol but NOT the cardiovascular risk.
To point:
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.043052
So much more cholesterol but no impact on inflammation or obesity.
Hmmm.
Clearly, fat is more complicated than we thought! Key differences are finally coming out.
Let's look at a big one.
The simplest hierarchy is that of omega 3 and omega 6.
We'll leave the chemistry to other sources (basically where bonds occur in the chain) and focus on the health effects.
The general public is starting to recognize some of the big players:
Let's focus on LA and ALA since these must be sourced from diet.
You hear about the ratio of omega 3 to 6 quite often. Why?
Because these both depend on the same shared pathway for metabolism:
https://www.eufic.org/en/whats-in-food/article/the-importance-of-omega-3-and-omega-6-fatty-acids
That's a great intro to the fats by the way!
The more omega 6 we take in, the less omega 3 we can process. So far so good.
So… let's take this back to our original charts. What changed?
https://pubmed.ncbi.nlm.nih.gov/34658440/
Well, that's not good.
Where is all this omega 6 coming from since animal products have a natural ratio more in line with our original intake.
https://pubmed.ncbi.nlm.nih.gov/34658440/
Goodness. We're slowly being poisoned…to cut costs.
Before we dive into the health effects, let's dive deeper into linoleic acid, the primary omega 6 intake.
First, take a look at linoleic levels by type of oil (very insightful):
https://www.news-medical.net/health/Oils-Rich-in-Linoleic-Acid.aspx
Look towards the bottom and you'll see the animal fats. There's coconut! Hmmm.
It's a fruit after all and olive and avocado also have similar profiles.
The interesting turn however involved soybean oil. Take a look at how big ag just fell in love with it!
See the timing on the inflection point? About 20 years before our health parameters went nuts.
A generation raised solely on seed oils.
What about soy's LA composition?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773065/
55% LA. Uh oh. Linolenic is also omega 6 so now we're 68%.
What's the problem with LA compared to other fats?
Oxidation. OXLAMs
Oxidated Linoleic Acid metabolites.
The percentage of linoleic acid in the fat profile of any oil directly drives how stable it is:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773065/
We'll get into it more below (the inflammation section) but increased LA consumption results in increased oxidative stress..system-wide (yes…in the brain as well).
https://pubag.nal.usda.gov/catalog/6122034
You're exhausting your primary detox pathway (glutathione) on a daily basis.
https://pubmed.ncbi.nlm.nih.gov/9844997/
That's not the only by-product of all this LA swirling around but it's a glaring example since oxidative stress is such a powerful force.
To show just how powerful this shift to Omega 6 is, let's look at just a few key systems knowing that every system is involved.
What on Earth is going on with testosterone?
The 1987-89 levels matches early century (1920-1934) levels. So…something really took a dip in the 80's. About 20 years after the big jump in seed oils!
This reflects a generation solely raised (birth, puberty, etc) with lots of linoleic acid.
It's only gotten worse from 2000-2020.
(yellow being latest and red being earliest)
Okay…obesity, smoking, and other attributes affect testosterone levels but even the researchers above admit they can't explain the drop.
Is there any data on omega 6 (like linoleic acid) excess and T loss?
Hello!
Among healthy, young men:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312216/
The reason is many fold: inflammation, upstream hormone changes, oxidative stress, etc.
What about estrogen?
This may speak to the testosterone changes:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846030/
LA drives estrogen which antagonizes both testosterone and progesterone.
This excess estrogen activity shows in specific E-sensitive cancers:
https://pubmed.ncbi.nlm.nih.gov/10806298/
Since BRCA1 is an estrogen-sensitive pathway, it's logical to assume that omega-6 fats are estrogenic in nature.
Linoleic acid can actually bind to the estrogen receptor which allows more estrogen to be available!:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846030/
Does this hold for the seed oils directly?
So…estrogenic. We could spend all day on hormones but we have to move on!
Big reviews:
Let's turn to probably the biggest difference between Omega 3 and 6.
The linchpin for much of what see with seed oils comes down to inflammation.
Omega 6 and 3 fats have almost opposite effects on the immune system:
https://www.mountsinai.org/health-library/supplement/omega-6-fatty-acids
What about linoleic acid specifically since it's all the rage on the food aisle?
Let's look at a few different tissues.
Let's start in the gut since it acts as a inflammation thermometer across the body (and brain):
https://gut.bmj.com/content/58/12/1606
Um...30%?? How is this not front page (right below the fried chicken sandwich ad. Oh...forget it).
And the little inflammatory assassins called cytokines?:
https://pubmed.ncbi.nlm.nih.gov/30672576/
Goodness. Too much linoleic acid (omega 6) increased inflammation (IL6), blood sugar, and other important inflammatory agents (TNFa).
"Systemic inflammation" is the key there as this drives aging and ALL illness.
Let's look at Rheumatoid Arthritis:
https://www.mdpi.com/2072-6643/14/5/1030/htm
Remember that Omega 3 and 6 compete for the same metabolic pathway.
A great deal of the inflammation comes down to Omega 3/6 ratio but we'll touch on more specifics as they apply to the areas below.
Let's turn now to metabolism.
We started this whole review with obesity.
So…what's the connection?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808858/
Goodness. Lowering the ratio of linoleic acid to alpha-linolenic acid "prevents" obesity.
There's actually a type of fat that burns energy…called brown fat. Babies have lots of it. Cold exposure increases it. So does Omega 3!
Our theory? Fish are rich in Omega 3 as a protection from the cold! Omega 3 is thermogenic (creates heat). Brown fat in humans is also thermogenic.
We digress…
Omega 6 intake directly affects this:
https://www.nature.com/articles/s41598-022-08125-z
To translate...people with more brown fat (burns glucose) take in less omega-6.
What about the whole insulin energy complex?
https://watermark.silverchair.com/D37.pdf
Okay…just for shits and giggles…let's bring back up the diabetes levels over the same time frame we looked at in terms of the rise of seed oils.
Hmmm…notice the hockey stick around 2000 also:
https://www.cdc.gov/diabetes/statistics/slides/long_term_trends.pdf
This zoom out helps:
Sure, sugar is not great but sugar went up quite a bit before diabetes followed (1850).
The real jump was right around the same period that seed oils were substituted.
We have a whole review on why glucose is so destructive in the body.
Remember that omega 6 increases the production of insulin and the eventual sensitivity to insulin (hello…diabetes!!).
Personally, looking at the research, the difference between our bodies in the 70's and now…is the addition of seed oils and omega 6 balances being way out of whack.
Don't take our word for it…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624939/
One more stop…an insidious one at that. If you wanted to make your food product super addictive, what would you do?
Let's introduce you to ghrelin. Your hunger hormone.
Literally, if it's released, you want to eat…regardless of nutrient absorption, satiety (being full), caloric intake, etc.
Hmmm….
https://pubmed.ncbi.nlm.nih.gov/30261617/
When you eat food that boosts ghrelin, you want to eat more. Talk about improving your market share!
Maybe that's why seed oils are in every processed food you can find (in addition to it being so cheap). You literally want to eat more and more regardless of being full.
What about the hormones that tell your brain that you're full? Leptin?
https://pubmed.ncbi.nlm.nih.gov/17647039/
Almost by design. Food scientists. You've been fighting an uphill battle!
Look…willpower is no match for appetite hormones.
It gets worse.
The heart of addiction revolves around substances that spike dopamine, our primary reward circuit in the nucleus accumbens.
Well well well...
https://www.mdpi.com/2072-6643/11/11/2785/htm
Dopamine is there to reward food, water, sex, etc. Things that help us survive. Linoleic acid is tricking this system just like alcohol, benzos, opioids, cocaine, and more.
Just like high fructose corn syrup:
https://www.jstage.jst.go.jp/article/bbb/77/11/77_130234/_pdf
That's fast! Like…still eating the meal fast!
Let's put that in context so you understand what's happening TO you.
Chocolate can spike dopamine by 50% if you really love chocolate.
Sex can spike dopamine by 100%
Okay…so 125% with linoleic acid.
Methamphetamine is close to 1000% (hence the brutal addiction risk).
Still…on par with sex from consuming linoleic acid!
So…trick your brain into thinking you're hungry and make it think you need it for SURVIVAL.
Dopamine isn't a pleasure neurotransmitter. That's more opioids and anandamide (our bliss molecule).
Dopamine is the "do that again" pathway. For increasing survival odds.
Do that again. Think about that when you're eating something with omega 6 and/or seed oils. Can you just have ONE potatoe chip?
So…just add linoleic acid in the form of seed oils to your product and it will be craved…on par with sex (actually higher).
Take a look at the ingredients now.
We got PLAYED.
Let's turn to the head…mental health.
We have big reviews on how brain inflammation is so important to mental health.
Better yet, early trauma, infection, or stress can ramp up the immune system in the brain and drive mental health risks later in life.
The immune system is the future of mental health tells the story.
Does the omega ratio figure into any of this equation since we know there's an inflammation piece?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611753/
Okay...that's odd.
They dug deeper in a study and found the following:
There's a fascinating cascade from omega 6's versus omega 3's.
It comes back to the inflammation piece.
Omega 6 are made into prostaglandins, pain signallers first and inflammatory signals beyond:
https://www.psychologytoday.com/us/blog/evolutionary-psychiatry/201701/your-brain-omega-3-balancing-the-o3-o6-ratio
Stress is key to our mental health response and addiction for that matter.
The whole stress cascade is set in motion by omega 6.
So…do we see results from this?
https://www.frontiersin.org/articles/10.3389/fnut.2022.841282/full
Our favorite superstar for mental health and addiction is BDNF, the brain's fertilizer.
Omega 3 directly supports the repair/growth pathway:
https://link.springer.com/article/10.1007/s00213-019-05258-4
We know that omega 6 (like linoleic acid from seed oils) crowds out omega 3. They compete!
Brain inflammation is the future for mental health.
So…
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01742-3
This is key for all mental health plus the neurodegenerative diseases like Alzheimer's, dementia, etc.
Let's zoom out to a 40,000 foot view.
Let's lead in with this:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533819/
Okay…so we just listed off the major killers of people.
We also see signs of inflammatory imbalance (asthma, autoimmune, arthritis, etc).
Mental health is front and center there as well.
We like to look at double-blind, placebo studies since there's some questionable research out there.
A study looked at replacing animal fats (saturated) with seed oil fats high in linoleic acid:
https://www.bmj.com/content/346/bmj.e8707
17.6% (seed oil) versus 11.8% (control) for ALL cause mortality!
A great deal of this was driven by cardiovascular risk.
There's a great review of the effects of linoleic acid (omega 6) and arteriosclerosis and cardiovascular function at this link but the net net:
https://openheart.bmj.com/content/5/2/e000898
It's all about inflammation and oxidative stress!
Stroke operates on the same principles but in the brain.
We just had an eye exam and it's fascinating! It's an internal lens to see how your vascular health is.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215739/
Multiple signs of damage to vascular health!
What about cancer?
Understand that the immune system is tasked with detecting and removing faulty pre-cancerous cells.
Inflammation is the key weapon of the immune system and we know that omega3/omega6 directly affect this pathway.
So…
https://www.sciencedirect.com/science/article/pii/S1665114616301423
They go on to look at research on different kinds of cancer.
Part of the issue may be high heat and seed oils.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155260/
Oxidative stress is highly destructive (more on it here) and heat just ramps up levels in cooking oil.
Remember…it's the ratio between Omega 6 and 3 (as we need both of them in the body).
In fact, studies can pinpoint the effects of changing this ratio:
https://iopscience.iop.org/article/10.1088/1755-1315/217/1/012055
MDA is a great tool for viewing oxidative stress and damage in the body.
You can actually test your MDA levels.
It's a signal for fat oxidation. The worst type of actors in the body (the real culprit for arterioschlerosis). We have a massive review on cancer.
Okay…we have to wrap at some time (if you've made it this far).
There's just so much data out there, we could write 10 fold on this subject.
There's a great review of lots of research here:
https://pinboard.opera.com/view/18bd6393-8296-4b72-9a1a-42eb050c6b4a
Again, carbs and sugar have their role but the advent of cheap seed oils and their skew of omega 3 and 6 fats is front and center for many of the ills that have spiked over the last 60 years.
Be well. Take care of each other. Take care of yourself.
Read those labels!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
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Powerful and safe ways to calm mast cell activation and histamine
]]>
We have deep dives on mast cell activation pathways but we wanted to get to the toolkit for offsetting this whole process below.
First...the mast cell cheat sheet:
Now, a quick look at the tools found in research that can actually reverse this hyperactivation of our immune system response without tolerance, addiction, and side effects.
Otherwise, we're just creating a worse problem in the future!
We'll run the gamut from steroidal hormones (especially important for women 40's and older) to unwinding the effects of past trauma/infection (very exciting).
Here's a quick list of tips for mast cell mitigation!:
Let's get started!
For women, you have to start with progesterone.
We have a deep dive but understand that progesterone is the master calming agent for immune response including histamine and mast cells.
In fact, estrogen drives the immune system while progesterone calms it.
It all goes back to pregnancy!
The amniotic sac is actually created by the father's DNA and as such, it's seen as a foreign entity by the mother's immune system which wants to attack it (the main role of histamine by the way!).
Progesterone calms this response..disabling the alarm so to speak.
That's why the autoimmune diseases can go into remission during pregnancy and
Check out our autoimmune review.
Also...huge ties to preemie births and low progesterone (immune system is winniing!)
Here's the issue…
And the percentage creeps up during the 40s and beyond. Hmmm.
Make sure it's bioidentical and oral. Prometrium (or generic) is an option. Work with your naturopath but progesterone is a total game changer for mast cell activation.
Interestingly for men, testosterone calms immune function as well (just not as pronounced)!
Okay… let's look at issues that apply to everyone (unfortunately).
This is the big one. The newer research is all around the immune system and epigenetic changes.
Don't leave! We'll explain it all.
Early trauma and/or infection (in utero or even past generations) can upregulate inflammation in the body.
Don't take our word for it:
A 30% increase in mast cell activity but this is only one aspect of a litany of insults from early stress and trauma:
Much of what we talk about below is either unwinding this heightened immune response longer term or calming the immediate histamine response now.
Our experiences (good and bad) affect the epigenome which turns our genes on and off.
Think of it as an equalizer for music. Dials (say bass or treble) get moved up and down and directly affect the sound of the music.
Your mast cell response is the music and we need to change those dials!
Check out our review on trauma or how the immune system is the key to mental health (and histamine response).
One more stop before we get into the tools.
The gut is our early detection system for outside intruders which makes sense since it's the site for first contact for most bacteria/fungi etc free-riding on our food.
The problem is that our gut constantly deals with chemicals and substances it has no clue what to do with.
Check out our review on CBD and the gut barrier to learning more.
The gut barrier is critical because when it's weakened, bacteria can escape into our bodies and the immune response including histamine is fast and furious.
In fact, a range of very common diseases are showing signs of bacteria influence including ones you wouldn't suspect:
Remember, the core role of histamine is to rid the body of foreign intruders!
This becomes a constant signal of intrusion across the body and it all starts from the gut (and occasionally the mouth, urinary/reproductive tracts).
Some of the tools below really focus on the gut inflammation states and the protection of the barrier.
Let's get into it!
Mag is awesome and so many people don't get enough since the conveyor belt from soil to food (ground bacteria and fungi) has been broken from pesticides and monocrop rotation.
Mag acts like a powerful calming agent across the body including its support of GABA, our primary "brake" pedal.
In fact, histamine and GABA are opposing forces in the sleep/wake cycle which is why histamine is so tied to insomnia (more here).
Mag deficiency directly drives mast cell activity (where histamine comes from).
Check out the review on magnesium glycinate. We focus on glycinate since it crosses the blood brain barrier and is key for mental health, sleep, and a range of excitability issues such as migraines.
We take 3 - 100mg daily to keep migraines at bay.
One note…when you're under stress, you just dump out magnesium via urine. It's a primary stress response buffer!
As for mast cells when mag drops:
https://www.sciencedirect.com/science/article/pii/S0925443900000181
Check out the big review on magnesium glycinate with practical guidance.
Next up…the system that balances our immune response.
We have huge reviews on CBD and mast cells or CBD as a mast cell stabilizer.
CBD isolate works within our endocannabinoid system which is tasked with balancing other key systems including the immune system (which features histamine).
The best part is that it doesn't push in one direction but calms histamine response when too high.
Speaking to this balance (don't worry…we'll translate!):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433789/
PPAR is a powerful pathway for "resolving" inflammation including histamine.
MDSCs are the counterbalance to mast cells. They basically push back on histamine response to bring it in balance.
Resolution! Again, this fits right into the endocannabinoid system's wheel house.
One important note…full spectrum CBD can have opposite effects due to the plant material.
There is a very different response between CBD isolate (by itself) and full or broad spectrum. More on full spectrum CBD versus isolate for histamine.
We take between 100mg-300mg daily as part of our regiment. CBD Isolate here. More on CBD for histamine here.
Also, check out CBD and asthma or CBD and psoriasis (autoimmune).
Next up…the forgotten steroid.
Vitamin D is actually a steroid. It governs over 1000 different processes in the body including DNA repair and yes…immune function.
In fact, it's a master regulator of immune response on both the good (fighting cancer/infection) and bad side (histamine and mast cell response).
Recent research from the pandemic sheds direct light on it:
https://covid19-evidence.paho.org/handle/20.500.12663/1569
Goodness. "Vitamin D deficiency results in mast cell activation"
For that reason, your doctor has been testing Vitamin D levels for years, right?
Wrong!! So many people are Vitamin D deficient and that's based on the ridiculous RDA levels of under 30 ng/ml. Endocrinologist want us closer to 70-80.
See our full review on Vitamin D (huge for sleep and mental health as well). Get tested. Get your levels up.
One more stop at our endocannabinoid system.
PEA is a backup player called in when the primary endocannabinoids (anandamide and 2ag) are running low. Exhausted.
Anandamide, named after the hindu goddess of "bliss" is a powerful backup when inflammation runs high.
It's there to "resolve" or bring it back down. CBD supports anandamide, which act like a big wet blanket of inflammation including histamine.
PEA is a backup backup to anandamide. Calling in the reserves!
The results:
https://www.frontiersin.org/articles/10.3389/fphar.2017.00857/
Full review here. You can supplement PEA here. CBD supports anandamide when low while PEA is a supplement to it. Very different from THC which pushes too hard/long as it mimics anandamide. This causes a rebound and tolerance longer term!
Let's turn to the gut now since it's a huge player in our histamine response.
We have a huge review on Medicinal mushrooms.
Fascinating effects across the range of mushrooms with huge implications on modulating or balancing our immune response.
Just a few examples….
Chaga:
https://pubmed.ncbi.nlm.nih.gov/29175507/
Cordyceps:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570676/
Again..we can go on and on as the a range of mushrooms show anti-inflammatory (including histamine) effects and powerful abilities to re-balance our immune system.
Read the big review here. We take a mix of medicinal mushrooms here.
Still in the gut…next up is berberine.
Berberine is a natural analog for metformin.
Both have powerful effects on calming gut inflammation and protecting the gut barrier (so bacteria, etc can't escape into the body).
Akkarmansia, a unique probiotic that increases with berberine or metformin, may be at the heart of these effects but either way, it's beneficial for mast cell activation issues.
https://pubmed.ncbi.nlm.nih.gov/30861392/
This is the short term effect. The longer term effect is reducing the "assault" so that the immune system isn't always code red.
Big review on berberine and this is the one we take.
Finally…the war party so to speak.
These players may have some benefit and are generally good for health anyway. There's a good review of different mast cell stabilizers here but the potential rising stars…
Let's jump in.
NAC supports glutathione, our primary detox pathway in the body.
Nitrous Oxide (NO) can suppress mast cell activity.
NAC's result there:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697744/
Vitamin C supports the glutathione pathway as well. See glutathione or oxidate stress.
The "good" fat can have a powerful effect on inflammatory response via its alpha-linoleic acid metabolites:
Fish oil is a great source of Omega 3 and watch out for the seed oils (and the highly industrial "vegetable" oil) with their Omega 6 profiles. Highly inflammatory.
We did a huge review on Omega 3's.
Quercetin (and fisetin) are fascinating plant-derived substances with effects across the inflammatory spectrum including…mast cells!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384425/
We really like "super" quercetin - called myricetin for it's powerful effect on dopamine!
That's a wrap! We focused on substances that don't build tolerance but calm "excessive" histamine response.
Keep in mind that histamine is a very important player in protecting us so we don't want to hammer it down (say with antihistamines) completely. Histamine is excitatory in the brain and key to the sleep/wake cycle.
We need it to be alert and engaged during the day. These players are backups when there's imbalance and that's ideal in such a complicated web as the immune system.
Don't forget....
The Cheatsheet:
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
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Easy walk-through on what research says about CBD and anxiety
]]>It's a classic mismatch.
The amount of research on CBD and anxiety does not match people's knowledge on the subject.
Huge misunderstandings on key points like dose, how to take, when to take, and the big one…what to take.
Time to bring everyone up to where research (NIH no less) sits. We may need a step-ladder!!
Here's the listing of the top 10 tips:
If you want a really eye-glazing review on CBD and the pathways of anxiety, go here.
We have 1000's of words reviewing every aspect you can imagine on CBD and anxiety. We'll link to our favorites towards the bottom.
Let's get started!
This is by far the biggest disconnect.
Many people will try 20-30mg of CBD for anxiety and wonder why it's not working.
Keep in mind that everyone's system is different and some may actually get some benefit with low levels but this does not match the research.
Most of the issue comes from people's expectations of what CBD will feel like. THC has crashed the party in this regard!
CBD does not create a "high". It doesn't build tolerance. It's not addictive. There's no rebound.
In fact, CBD has been found to counter THC's effects on that front and this is the true meaning behind the term "entourage effect" from the Israeli Godfather of CBD research.
So…how to look at CBD dosage for anxiety?
First, a general wellness test is around 30-50mg. This is to see how you respond and dispel any worries!
The higher level of CBD is generally around 300mg daily based on research.
This is peak neurogenesis, the key to long-term improvement.
We'll look below at times of intense stress/anxiety below.
Many people find benefits at 100mg daily so you really need to play with the range to see how you respond.
This definitely doesn't match 30-ounce bottles with 250mg total CBD out on the market!
That's about 9mg per dropper. Total ripoffs.
Check out our Top 10 Tips on CBD Dosage Guide for more.
The type of CBD is another big issue.
Most of the market is pushing full or broad-spectrum CBD.
This is usually CBD added back into hemp oil with or without other cannabinoids and/or cannabis plant material (terpenoids, etc).
What's not being discussed, especially in terms of anxiety, is histamine.
Histamine is excitatory in the brain…it actually eats up GABA, our key calming pathway (and target of benzos - see CBD versus benzos here).
All the plant material in full or broad-spectrum can make anxiety worse or cause it! Not to mention insomnia (see histamine and insomnia).
Most importantly, almost all the research is on CBD isolate…CBD by itself.
We have a whole review on full-spectrum versus CBD isolate for anxiety.
It's the #2 biggest disconnect on the market for people dealing with anxiety.
Let's get practical now.
CBD has a peak level in the blood after 4-6 hours. This times perfectly with meals (more on that below).
If 300 mg per day is the peak level for neurogenesis (key to mental health and addiction) 100mg after each meal would hit this target and spread the level out through the day.
Some people will save the third "installment" for nighttime (see CBD and sleep).
CBD should be taken at least 4 hours away from medications (check with doctor or naturopath) so skipping one of these and having 150mg/150mg for the other two would address this.
Again, everyone's system is different and you may get benefits at 100mg daily. In which case, just break it up!
Of course, you can take it at one time (strong safety profile up to 1500mg in NIH research) but test and adjust.
For how long?
There are two critical pathways (of many) that directly impact anxiety:
GABA (target of benzos) works very fast…almost immediately.
Serotonin builds over time which is why SSRIs don't kick in for 2 weeks (till tolerance kicks in).
It turns out that the real magic behind serotonin is actually BDNF, our brain's fertilizer and that takes time to "build". Literally building new brain connections!
CBD supports both pathways in a feedback mechanism which is why you don't see tolerance, addiction, or bizarre side effects like with anxiety meds.
Big review on CBD versus benzos or CBD versus SSRIs.
Let's tease out ways to make CBD work best for anxiety.
Most CBD is taken orally and the oils are generally how we can achieve levels actually shown in research.
Here's the deal. The liver processes CBD (and about 60% of medications).
Very little CBD gets past the gauntlet of the gut and especially the liver.
To counter this, you can take CBD after meals. Why?
The liver also breaks down fat in our meals and if it's busy with this task, more CBD gets through!
So…CBD after meals can boost the bioavailability by significant amounts.
That combined with the next key trick can drive up levels by 4x's.
With CBD oils, holding the oil under your tongue for up to 60 seconds does two things...
The real impact is allowing more to absorb before the gut gets to work on it.
Again, between this method and taking after meals, research shows a 4x's boost in availability.
That means you can take less and save money!
Okay..what if we have something really stressful coming up (social situation, etc).
There's an interesting study on CBD and public speaking that we can lean on.
Basically, they gave CBD to people with diagnosed social anxiety before public speaking.
Literally the worst fear of anyone with social anxiety (or without apparently).
Check out the full CBD and public speaking study.
What can we take from this if we have a very stressful situation coming (or going)?
600-800mg mirrors levels in research for more serious issues so it's definitely within bounds.
If you hold the CBD oil under your tongue, it can speed availability if you don't have 1 ½ yours to wait!
Peak CBD is about 4-6 hours after usage.
This brings up an interesting strategy if we're new to CBD.
Mirroring what we see in studies on drug withdrawal (opioid, alcohol, nicotine, etc), there's an interesting pattern:
Beyond that, you can test how you feel and always adjust accordingly.
Anxiety can be overwhelming so there's merit in hitting with a higher dose at first to right the ship and then settling down to the 300mg since neurogenesis and BDNF are the key drivers for long term change.
Along the way, there are other tools to look at which also don't build tolerance.
We have a visual guide to anxiety tools here but the cheat sheet:
That last one is a great lead into to the final section!
We have massive reviews on the immune system and mental health or early trauma and mental health.
Early trauma or infection (even in utero) can cause havoc in almost every system tied to anxiety:
And much more!
Getting to the root of this is critical to affecting long term change.
The mushrooms are interesting to rebalance these effects since the mark-up from early trauma/infection is primarily "written" in the immune system's record.
It's important to understand "why" we get anxiety!
Okay…that's a wrap. We have lots of research backing all these sections with dozens of NIH studies.
Be well. Take care of each other. Take care of yourself.
The Ridiculous Guide to CBD and Anxiety
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>Understand how trauma, infection, and stress leave marks on our health...which can be erased!
]]>Out of the 1 million+ words on research we've written, the following 2000 words may be the most important.
We have deep dives with the research that supports everything below here:
Dozens of NIH studies but… it can get overwhelming.
This review is our attempt to slow-cook this information in an easily accessible format to reach the widest swath of people.
For good reason.
Spending 2-3 hours a day in NIH studies, we keep coming across the same dynamic that secretly guides all things health and mental health.
Outside of pretty significant genetic differences which the body usually finds workarounds for, steroidal hormone loss and early trauma/infection/stress are THE drivers of how we manage stress and the world.
The two are even intertwined!
The most exciting part is that we can actually "overwrite" a great deal of the latter since it's encoded in our immune system and the epigenome (don't worry…we'll explain it all).
Let's get started…here are the topics:
Let's get started! Stay with us…this is the biggest key to markedly changing your health trajectory.
Before we get into the really exciting new frontier of editing your past, we have to take a quick detour to steroidal hormones.
After all, they're just for reproduction.
Not!
It's probably the greatest failing of our healthcare system bar none. The average doctor has a few hours of instruction on them but mainly around reproduction.
They are so much more!
Estrogen and Testosterone are powerful drivers system-wide of:
One example (of thousands…every cell in your body has receptors).
Looking at the brain, they both drive serotonin…the manager of ALL human behavior.
Serotonin is your new best friend:
Serotonin is the target of SSRIs, but they build tolerance (see SSRI review).
Progesterone is fascinating for women. It actually ramps up to protect the amniotic sac from being attacked by the woman's immune system.
Generally, it calms inflammation and pushes back against estrogen. A huge supporter of GABA, our brain's "brake" pedal (target of benzos).
It drops 1% each year and hits 50% by age 40. Hello, autoimmune and anxiety, etc.
That's just a smattering. Gut. Heart. Bone. Muscle. Organs. Brain. You name it…they are intimately involved in supporting every cell!
We did deep dives here:
Here's the rub and why you're probably not on them (if your doctor even tests the levels!).
We looked at the estrogen one specifically in our guide above but the new Bijuva study showed results were actually BETTER with bioidentical oral estradiol/progesterone.
You'll probably have to fight with your doctor (or find a new one) to get Estrace, Prometrium, or bioidentical Testosterone.
Put up your dukes! Check out steroidal hormones and longevity. It really is the first shoe to drop!
That's just a function of aging…we're all on the same boat and it's taking on water. Get your levels tested and supplement as needed. Bioidentical only!
Lots of research in the links above.
Also, Vitamin D is a Steroid! So many people are deficient and it manages around 1000 "transactions" in the body including DNA repair.
Get tested. Support as needed. Check out the review for more guidance.
Let's now turn to the exciting piece with a focus on mental health (Descarte ruined us…the body and brain are cut from the same stuff).
We need to introduce the most exciting playing field in medicine's future. Your epigenome.
In the next few years, you'll see headlines about massive companies (Calico, Altos labs, etc) promising (and probably delivering) on reversing aging. Maybe even back to age 25!
This centers around new understanding of the epigenome.
Stay with us…it's pretty cool!
You have your DNA. Think of it as a hard-coded set of instructions to run every one of your cells.
It doesn't (shouldn't) change much barring mutations.
That's the "nature" side of things. What you're born with.
Then there's the much more exciting "nurture" side. This resides on the epigenome, a set of instructions that determine how those underlying genes are expressed.
Which genes? How long? How much? When?
The difference between your body at age 25 and 50 lies in the epigenome and pretty brilliant scientists may have stumbled on how to remove the "edits" that accumulate as we age.
More on this Yamanaka Factor Research.
That's exciting but our interest in this "setting" is more…practical.
Let's turn there now.
The brain is essentially a prediction machine. Its immediate goal is to predict situations that will help or harm your chances of survival.
This prediction is based on past experience!
Little "markups" or edits will be made to your settings based on what happens to you.
In fact, the markups can happen in utero or even be passed down from past generations (up to 10 generations in some studies)!
Think of the EQ setting on a stereo. You can boost bass or treble to change the sound (epigenome) for the exact same song (DNA).
The effects are powerful and directly drive health and mental health.
It turns out that infection (viral or other), trauma, and stress early in life can cause life-long shifts.
This trickles down to key pathways we can see (and feel) directly:
Goodness…what a cluster-you-know-what!
Why would the body put our backs to the wall this way?
Prediction machine.
If things were bad (or dangerous or without food or abusive, etc) in the past, the brain wants to be ready. Settings adjusted. Be vigilant. Be on guard. Be…anxious!!
Here's where it gets even more interesting!
How would stress for Holocaust survivors be passed down to later generations and drive increased risk for mental health issues and changes in metabolism??
The DNA isn't changing. There must be a way for this information to pass down from generation to generation.
Very similar to a recording of past interactions with different viruses. Hmmmm. The immune system!
New clues are teasing this out.
For example, new research on psilocybin (which will revolutionize addiction and mental health) shows that the long-term effects were due to epigenetic changes to genes….in the immune system!
Insult to injury…early trauma, stress, and infection can also reduce…steroidal hormone function!
One note…the immune system is super complex but it responds to infection or psychological stress about the same!
Childhood abandonment ramps up inflammation just like strep throat!
Understanding this is very important.
That all sounds pretty depressing but it's so so exciting!
Why??? Because we can calm the storm!
There are ways to re-tool the immune system and "forget" the past edits that drive physical and mental health issues.
One important warning!
We MUST avoid tolerance and addiction.
Tolerance is what happens when a substance (drug, med, or supplement) pushes a key pathway in one direction.
The body strikes back! It will actually reduce receptor activity and numbers for that given pathway which means we end up worse off than when we started.
You see this everywhere:
Some of these also spike dopamine which drives addiction but tolerance is enough to make you miserable.
So…our toolkit to rebalance our immune system and also support key pathways:
A quick intro since we have deep dives for each.
Mag is our mineral stress response buffer. A metallic wet blanket for inflammation, stress, and glutamate!
Many people are deficient because mono-crop farming and pesticides kill the conveyor belt (bacteria and fungi) that move it from soil to food.
Glycinate gets across the blood-brain barrier best.
It directly supports GABA, calms glutamate (which just leaks out from hyperactive immune response), and calms inflammation.
Mag works fast and slow. 3 x 100mg daily is great support.
We use this one here. More research here.
Sure, this is close to our heart but only because the research is ridiculous.
CBD is a feedback player in our system that balances other key systems including:
Again, this occurs since the endocannabinoid system is tasked with balancing the immune, endocrine, and nervous system.
No small task and CBD doesn't build tolerance like THC does. It supports when low!
Its support of BDNF may be the biggest coup since BDNF is THE key to mental health and addiction!
Research shows that peak neurogenesis is at 300mg daily.
We use this one here and more research herek regarding edits to our past.
Our distant cousins are so fascinating for retooling our immune response and supporting repair/replenishment.
They support BDNF, calm inflammation, and affect so many different pathways.
There's a great blend which we use here.
Lion's mane, Reishi, Turkey Tail, and more all in one capsule.
Learn all about medicinal mushrooms and mental health medicinal mushrooms and health.
Vitamin D is actually a steroid…one we get from the sun!
But we're not in the sun like our ancestors and our D reflects this.
D is a massive manager of the immune response, sleep, and mental health.
1000s of chemical processes and a slew of DNA repair pathways require D to work.
Get your levels tested and aim for 50-60 ng/ml.
Then question why your doctor never tested you before!
D is also critical for your steroidal hormones to function correctly. Go figure.
Learn about D here.
So much exciting research is further South…to the gut!
Berberine is a powerful player to calm inflammation there.
The gut works like a thermostat…setting the inflammation setting for the rest of the body and the brain via the Vagus Nerve.
Gut inflammation and breaks in the gut barrier cause a host of different issues to the…host!
Learn all about the vagus nerve support and berberine.
This is the one we use.
NAC is a powerful supporter of our entire detox pathway which centers around glutathione.
More importantly, NAC acts like a sink for excess glutamate (the brain's gas pedal).
When the immune system is ramped up, its sentinels called microglia just leak out glutamate which is toxic to our neurons when excessive.
There's interesting research on NAC and mental health reflecting this calming effect.
This is the one we use, and there's more research here.
We covered this!
It must be bioidentical. You can get your levels tested (the Dutch test is the best option) and adjust accordingly.
Don't go for the "your levels are fine for your age" if older. Do you feel the same at 50 that you do at 25? No!
Find a better doctor. Better yet…a naturopath who actually learns about hormones.
Finally…we can dream…
The key ingredient in magic mushrooms is a total game-changer for everything we discussed above.
It's as close to an epigenetic "eraser" that we have till Yamanaka factors just scrub it clean.
We even looked at whether psilocybin is a form of Yamanaka factor effect we can have now.
It's not legal yet but that's coming and the question will then be…why did they suppress the research and access for 60 years with a tally of suffering and loss that's unrivaled?
Yes…it's that powerful. A new study on heavy alcohol use saw an 88% reduction!
Pitchforks time.
If you're not comfortable with psilocybin when it comes online, CBD does the same thing…just at a slower pace (BDNF is the big "editing" player).
We looked at CBD and epigenetic remodeling but its effect on "fear extinction"...essentially "forgetting" traumatic experience write-up is a great example.
That's a wrap!
You are now at the cutting edge of mental health and health generally. Not just masking the symptoms while making the underlying storm worse.
If you want to read the deep dive with dozens of NIH studies, enjoy here.
Welcome to the future. Take it back from the past!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>
Third Party Test Results - Transparent , Complete, and....Readily Viewable!
Indigo Naturals aims to be transparent and provide our customers with the information they need to feel confident in their purchases with us.
No pesticides, fertilizers or other chemicals!
We use the supercritical carbon dioxide extraction process and never use solvents.
Each batch of Indigo Naturals CBD oil goes through rigorous testing and following strict hemp production laws.
The Test results are for the final formulation found in each bottle. Each batch is tested for CBD potency and purity.
If you need help understanding these reports or have questions, please email us at: support@indigonaturals.net
Don't worry...we'll walk through how to read the reports by section.
This should match the number on your product. Each batch is tested separately.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
New research is pointing to 300 mg/day as the peak dosage for neurogenesis, the process of brain repair so critical to mental health and addiction.
This quickly becomes expensive!
Since we found CBD as a result of trauma and suffering, we want to go further.
So...
Set up a subscription and save 10% right away and ongoing!
You can change or cancel (or restart!) a subscription anytime! You'll have access to your account via the account icon at top of any page or just reach out to us via message button or support@indigonaturals.net
It's easy to setup...when making a purchase, just click on the subscription box:
That's it. 10% off your favorite CBD.
Let's see if we can one-up that option.
When you refer a friend to Indigo Naturals CBD, they will receive 20% off their first order and you will receive 20% off your next order.
This option is part of how we're able to offer high quality CBD at lower cost per mg of CBD. We can't advertise CBD so you're the only way to get the word out!
It's PERSONAL for us!
Leave a review on a product page or on Google here.
You will receive a 20% off promo code generally within 48 hours or EACH review.
Just email us at support@indigonaturals.net when review is submitted and we'll get the discount code right over to you!
The google option is really important to help get the word out!
Again, we were reeling from a traumatic health event when we found CBD so it's really important to us that we make this option as affordable as possible for the best quality product.
There's lots of questionable CBD product out there.
Our goal is simple:
The only way we can really do this is with our awesome customers spreading the word. Getting back to Health...is a movement!
]]>We can help with any website or production questions plus send specific research based on your needs
]]>
Please contact us regarding questions on products, orders, or general CBD information.
1 million+ words of research across a range of topics.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
]]>How CBD went from My Story to Our Story
]]>Our CBD Story Started With Trauma
One door opens and another one closes.
In our case, the closing door was slammed shut by a brutal perimenopause in 2018.
Multiple doctors. Benzos. SSRIs. Heart and blood pressure meds. Sleep drugs. You name it.
Almost broke me.
The saying goes…a healthy person has a 1000 wishes. A sick person has but one.
This opened the door…really a scramble through it to learn everything we could. About everything we could.
Deep dives into NIH research on hormones, the gut microbiome, neurotransmitters, and key pathways tied to what I was feeling.
It was truly sink or swim.
After the horrible withdrawals and weaning from benzos, SSRIs, and even the blood pressure meds, it became clear that there are only a few options that don't build tolerance.
Tolerance is the enemy!
If there were chapters to our CBD story, it might go like this:
It's a quick read but our story is quickly becoming 1000's of people's way back to health.
One of the tools we came across in our journey was CBD (and our pantry is littered with various bottles, vials, and elixirs…Thank goodness the witch hunts are over :)
It took some deep dives as we're not pot people but the research was ridiculous.
CBD has nothing to do with the standard responses from cannabis!
If you tease out the subtleties of how they work, you can't help but get excited about CBD across a range of pathways.
A quick detour to explain why we were practically thrown through that door!
Our bodies have an ancient (estimated at 600 million years old) pathway that's tasked with balancing every other system.
The endocannabinoid system.
There are two big players:
Anandamide is a backup supporter when other pathways are stressed, exhausted, or under duress.
It's a chemical version of resilience!
Here's the deal to understand…
THC mimics anandamide and fits into the same CB1 receptor.
The problem is that it hits too hard and for too long. Hence, the side effects (both desired "high" and not).
That's tolerance and your natural anandamide levels slowly goes down with prolonged use.
You end up worse than when you started!
Anandamide's role is to keep us "just high enough".
Think of those days where you feel really good. If you're on this page, those days may seem far in the past.
What about CBD?
This is why you don't see overdoses with CBD and it can even have different responses depending on the state of the system.
One of our favorite example from research (of dozens across very different pathways):
The latter makes sense once you realize that the immune system kills off faulty cells with inflammation (technically oxidative stress). See CBD and cancer
See why we got excited?? That's a very odd response. A gift down here really.
We have 1 million+ words of deep dive into 100's of different pathways and health issues. (search here).
A few key pathways...
So….we were excited back in 2018. Now how to buy CBD?
We did what most people do. We found the biggest brands online that have some type of 3rd party testing.
3-4 of them to be exact. The almost full bottles probably linger somewhere in the house.
There is a big push for "full" or "broad" spectrum CBD on the market.
All the plant material. Other cannabinoids. CBG/CBN, etc. Terpenoids.
The "entourage effect" which as we now know is misused from its original meaning.
I had a terrible response to all of them. Classic histamine (allergic) reactions.
Remember that I was in the throes of perimenopause and progesterone was rock bottom.
Turns out that progesterone calms the immune system and that includes histamine response!
I'm not alone!
Full-spectrum CBD may not feel so hot for those people. 75% of those people are allergic to THC as well.
I almost gave up…I actually didn't feel that great on CBD but this didn't match the research.
Finally, I stumbled on a CBD isolate brand in coconut oil.
Game changer!!
Totally different response and exactly in line with what I originally expected.
There's so much marketing for full or broad spectrum with almost no thought (or research) on the powerful histamine pathway which is curious to us.
We did a massive review on histamine looking at anxiety, insomnia, and pain (sound familiar??).
Histamine is excitatory in the brain and nervous system.
It eats up GABA, our calming agent (target for benzos).
That's only:
Pretty much 80% of why people take CBD to begin with.
Goodness. Look at the reviews on the product pages and you see tell-tale signs of this same trajectory for many people.
So…how does this go from My story to Our story??
The more we learned, the more excited we became.
CBD isolate was a life raft when I was drowning and 1000's of hours in NIH research just continued to cement this relationship.
But we wanted high quality CBD at a price per mg that we could afford.
There was some quality CBD on the market but it was very expensive.
It needed these essential requirements:
This was just the starting block.
CBD isolate of course since 99% of the research is on CBD by itself and this matches the histamine angle.
Then there was cost.
We found that we could provide higher levels of quality CBD with our 6000mg bottle at 2-3 cents per mg of CBD BEFORE discounts up to 50%!
Again, it helps to read the research and ½ the dropper of the 6000mg is 100mg. 3x's after meals hits the 300mg goal.
Lots of crappy product out there with 250mg…in a whole bottle! And it's expensive. Ripoffs.
On top of this (since we've stared into the health abyss), we added ways to save up to 50% via subscriptions, referrals, and reviews.
Sure…it's a business but go through one of our 100's of reviews and tell us this isn't more of a brute force to give back.
Some we're proud of:
In fact, we have dozens of reviews on non-CBD tools that we come across such as:
And on and on.
If there's something we come across that supports key pathways without tolerance, we're Periscope Down! Deep dive.
We were flying blind in the beginning…piecing together everything we could and trying every supplement out there. Most of it causes tolerance or histamine issues.
All the research here hopes to be Air Traffic Control….back to health.
At IndigoNaturals, we love to send out personalized research based on your situation…just email us at support@indigonaturals.net or use chat option bottom/right.
It's our way of giving back since our one wish was granted.
Be well. Take care of each other. Take care of yourself.
Our personal story really began here: Dre's Story.
(we're not big fans of getting our pictures taken :)
Andrea Goodacre Jarvis (left) and Sharon Gray (right) - IndigoNaturals founders
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