CBD and the Mechanisms (plural) of Anxiety

CBd and the mechanism of anxiety

 

We started 100,000 words ago with our top-level review of CBD benefits for anxiety.

 

After that, we did deep dives into many specific attributes that drive anxiety.

 

The actual gears and widgets!

  • Glutathione and anxiety
  • Microglia and anxiety
  • Hippocampus neurogenesis

 

Just to name a few of dozens.

 

Some were downright fascinating!

 

After dozens of articles following any thread we could find in NIH research, it's now time to revisit the mechanism of anxiety.

 

We're in a much better place to do so after looking at the various pieces that feed into it.

 

Some of the research is brand new (within the last few years if not months).

 

Other research on the mechanism of anxiety has been around for a while, albeit it, with revisions and tweaks.

 

If you really want to address anxiety, you first have to understand its roots.

 

Certain "pathways' came up again and again so we're going to summarize that here.

 

We're going to cover these areas: 

  • Why anxiety
  • What is the brain area mechanism for anxiety
  • What is the neurotransmitter mechanism for anxiety
  • What is the stress and inflammation mechanism for anxiety
  • What is the gut and microbiome mechanism for anxiety
  • What is the hormonal mechanism for anxiety
  • Finally...what is the mechanism for anti-anxiety medications
  • What is CBD's mechanism for anxiety
  • How much CBD for anxiety based on research
  • What's the best CBD for anxiety 

 

LIke we said...no stone unturned.

Why anxiety

Let's start with the basics.

 

Why do we even have the feeling of anxiety?

 

How can that possibly be needed?

 

It's downright essential in healthy proportion!

 

In fact, we looked at people who can't feel anxiety or pain in this review here.

 

They are missing a gene called FAAH (happens to be an endocannabinoid) which eats up Anandamide, our "bliss" molecule.

 

The woman in the example can not feel anxiety or pain EVER!

 

Most people with this extreme genetic deficiency do not survive.

 

Pain and anxiety are there to steer us away from danger!

 

Obviously, there's a spectrum of response out there as evolution asks like a bookie...taking all bets.

 

Some people will fare better in a safe environment if they are adventurous and fear nothing.  We all have THAT cousin.

 

Those same people may not be around long in more dangerous situations.

 

No worry...a whole other subset of people are more cautious and will do just fine.

 

Unfortunately, the rules of survival we're written 10's or 100's of 1000's of years ago.

 

Our anxiety response still functions but there are new dangers.

 

Some of them are unknown to our body (pesticides, chemicals, drugs, infections, antibiotics, etc).

 

Others are chronic...stress and inflammation that never goes away.

 

As with all things in our body, it's half genes and and half environment.

 

For example, people with high levels of NPY who came back from war did not develop PTSD while those with lower amounts, were more likely to respond poorly.

 

Check out CBD and Performance Anxiety 

 

That's on the gene side.

 

Then there's trauma, chronic stress, infection...things we can't control in our environment.

 

In fact, the effects of past trauma can go back generations!

 

It's called epigenetics and you carry that "coloring" in your genes right now.

 

The good news….we can also affect these same epigenetics with our actions now.

 

That's what we'll get into towards the end.

 

For now, just know that there can be root drivers of increased anxiety: 

  • Trauma, infection, chronic stress
  • Genetic variations that weaken or strengthen key pathways

 

The knock-on effect from these conspirators and insults then show downstream in various pathways.

 

That's where we're going to focus since we can actually have some impact there.

 

We'll start in the brain (of course!).

What is the brain area mechanism for anxiety 

The anxiety circuit in the brain is pretty well established (compared to the gut, etc).

 

We've covered it in detail at our CBD and general anxiety disorder article but a quick recap.

 

You have key players: 

  • Amygdala - our emotional and fear processing center
  • Prefrontal cortex - our rational constraint on the Amygdala
  • Hippocampus - The "decider" on what should elicit a fear response

 

There's lots of connectors between these including the ACC (anterior cingulate cortex) and white matter tracts in general.

 

Most of the research points to some aspect of the following happening in the anxiety mechanism. 

  • Too strong a response from the amygdala
  • Too weak a reply from the prefrontal cortex
  • Weakened response or damage in the hippocampus
  • Poor activity in the connecting tissue

 


Remember how we talked about "past insults" driving the anxiety mechanism?

 

Our brain is plastic.

 

This word just means that it changes based on inputs over time.

 

In fact, taxi-cab drivers were found to have enlarged hippocampus areas which makes sense once you know that spatial mapping is primarily held there.

 

You can also learn fear response.

 

We see this all over the research from general anxiety to PTSD: 

Notably, many neuroimaging studies have demonstrated that patients with PTSD have greater amygdala activation compared to controls  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882379/

 

Chronic stress is the same thing as trauma...just in slow motion: 

We found a mechanism for the effects of chronic stress on amygdala activity, specifically that chronic stress increased excitability of LAT pyramidal neurons recorded in vivo.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882519/

 

The word they used was "hyperexcitability". 


"Stress" can also take the form of infection in terms of how the brain's immune system looks at it.

 

Especially if during key times of brain development: 

 Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume 

https://www.pnas.org/content/pnas/109/20/E1312.full.pdf

 

Check out CBD and cortisol for anxiety here.

 

The opposing and constraining area of the brain is the prefrontal cortex.

 

This is the last brain area to develop (usually wraps in our mid-20's!) which is why the teenage years are so fraught.

 

Check out CBD and teen anxiety to watch this fascinating and horrifying process unfold!

 

What's the importance of the prefrontal cortex (sits right behind your forehead)?: 

In particular, recent studies suggest that the prefrontal cortex of the brain normally “gets a grip” on excessive anxiety by moderating the activity of a more primitive region known as the amygdala. When this prefrontal-amygdala connection is weak, excessive anxiety can be the result. 

https://www.dana.org/News/Details.aspx?id=43024

 

This area is literally shut down for remodeling during puberty.

 

Go figure!

 

Finally, the area of the brain that is most vulnerable in the anxiety mechanism.

 

The hippocampus.

 

It's the seat of memory and a master regulator or our fear and anxiety response.

 

There are actually two opposing sections that mediate the very adventurous/cautious decision we started with.

 

It's like a risk/reward circuit.

 

Check out CBD and hippocampus neurogenesis to learn more.

 

The key to our story here is this...the insults we mentioned above hit the hippocampus the hardest and the net effect of this can be anxiety or depression (among other mental health issues).

 

That's a good summary of the brain anxiety mechanism.

 

Let's now look at the chemicals that do all the heavy lifting within and between these areas.

What is the neurotransmitter mechanism for anxiety 

This is easier as we can take our cues from anti-anxiety medication targets (while avoiding some of the nasty side effects).

 

There are two main classes of anti-anxiety medications: 

  • Benzos like Xanax, Ativan, and Valium
  • SSRI's like Lexapro, Zoloft, and Effexor

 

  • Benzo increase GABA in the brain.
  • SSRI"s increase Serotonin in the brain.

 

Both neurotransmitters are incredibly powerful and essential workhorses in our nervous system.

 

The issue is that the medications have pretty severe downsides.  See CBD versus anti-anxiety medications here.

 

Let's focus on what they do right since that speaks to CBD's effects which we'll talk about later.

 

Benzos increase GABA which has an immediate anti-anxiety effect.

 

They also hammer dopamine which is why they're so addictive.

 

GABA is the "brake" pedal of our brain not only in terms of activity in the neurons but feeling calm (and eventually sleepy and catatonic with too much).

 

How do we figure this into our anxiety mechanism outlined above (past/current insults and genetic susceptibility)?

 

Think of a car where the gas pedal is jammed on or where every acceleration is pedal to the metal.

 

Jammed on is a pretty good representation of chronic stress.
Pedal to the medal and slamming on the brakes is akin to trauma and infection.

 

Your genes in the anxiety circuit can be a lead foot driver or cheap, crappy brake pads.

 

We're burning up GABA too quickly and easily.

 

Okay okay...we'll stop with the car metaphors but it helps to picture what's going on.

 

Check out Can CBD boost GABA for anxiety to really understand that pathway.  

 

There's an interesting review of how the different types of stress (chronic, acute, traumatic, psychological, etc) directly affect the Amygdala via GABA.

 

Their summary: 

studies showed that exposure to acute or chronic stress can induce morphological and functional changes in amygdala. These changes in amygdala can cause individual susceptibility to anxiety disorders 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103381/

 

Next up, we have serotonin (and BDNF).

 

We're told that serotonin is our "feel good" neurotransmitter but that's a bit misleading.

 

It's a workhorse transmitter in the brain and nervous system.

 

If any critical transmitter is too high or low, you're going to feel pretty crappy.

 

The side effects of too little or too much serotonin are devastating.

 

Check out CBD versus SSRI's for serotonin and anxiety to get more details.

 

Why even prescribe SSRI's which boost serotonin then for anxiety (especially since it's more in line with depression treatment)?

 

Great question!

 

Here's the part that your doctor isn't saying (or just plain doesn't know).  

 

The real lever that serotonin is pushing deals with brain repair!

 

Same thing for BDNF.  

 

If stress, whether acute or chronic destroys the brain (actual tissue loss), serotonin and BDNF are key to replenishing and building new brain.

 

It's called neurogenesis.

 

For a percentage of anxiety and depression sufferers, you can think of this being the result of a brain that's losing connectivity.

 

There are fascinating studies where neurogenesis effects from serotonin are blocked and the anxiety continues.

 

Check out the CBD and serotonin article for a full explanation.

 

This is the repair side of things.

 

Let's look closer at the damaging part.

What is the stress and inflammation mechanism for anxiety 

How do we get to that point where we have brain area irregularities and neurotransmitter imbalances?

 

A great deal of research points to stress, inflammation, and infection.

 

We covered each in detail here: 

 

Let's give just one example from each.

 

First stress.

 

Long term, chronic stress will depress GABA levels which is directly tied to anxiety. 

Chronic stress causes disinhibition of the hypothalamus-pituitary-adrenal axis. Consequently, the brain is overexposed to glucocorticoids which in humans may precipitate stress-related disorders, e.g. depression. 

https://www.ncbi.nlm.nih.gov/pubmed/1535533

 

The HPA axis is our fight or flight response system to fear and stress.

 


Inflammation is just our immune response to infection, toxins, and even stress itself!

 

There's an entire system at play involving strange actors like microglia (our immune cells in the brain), cytokines (little inflammatory assassins), and a host of very complicated chemicals.

 

The net effect is that an overactive immune system (triggered by a host of different insults) can attack the brain the same as stress itself.

 

You'll see the tell-tale signs throughout the brain: 

anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord) 

https://www.ncbi.nlm.nih.gov/pubmed/26296565

 

The microglia are even more fascinating.

 

If overactive, they literally attack our brain cells which causes the retrenchment we discussed above. 

 

It's not just infection though.

 

One study found that psychological stress caused the ramping up of microglia and a specific cytokine, IL-1B: 

Collectively, the development of anxiety during stress was caused by microglial recruitment of IL-1β-producing monocytes that stimulated brain endothelial IL-1R1.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628107/

 

Check out CBD and microglia for anxiety here.

 

It's all inter-related and if our repair systems (serotonin and BDNF as examples) aren't functioning adequately, we can literally have brain tissue loss and anxiety (or depression) response.

 

As for infection, we now have to travel further south in the body.

 

To the all important gut!

What is the gut and microbiome mechanism for anxiety

A great deal of our immune response to inflammation and infection starts in the gut.

 

The microbiome or the trillions of bacteria that populate our gut are key to moderating response to a host of insults.

 

This is the only area outside of the brain and spinal cord where we have neurons.

 

There's a reason it's called the second brain.

 

Here's just a taste of what our gut bacteria do for us: 

  • Make vitamin b12, thiamin, riboflavin, and vitamin K.
  • Make over 90% of our serotonin (the "feel good" neurotransmitter)
  • Synthesize GABA (calming neurotransmitter) and Glutamate (excitatory neurotransmitter)
  • Turn genes on and off in our gut and immune system 
  • Send signals to the brain to control hunger, saity, blood sugar, energy usage, and more 

https://howcbdworks.net/how-does-cbd-work-for-microbiome-gut-bacteria.html 


Did you catch the serotonin and GABA in there?

 

The effect gets more specific for anxiety.

 

Some good strains can help while bad strains can cause anxiety havoc.

 

There are lots of studies of animals raised with no microbiome.

 

Researchers can then turn anxiety on and off with specific strains: 

Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. 

https://www.nature.com/articles/nrn3346

 

Check out CBD and probiotics for anxiety to find out which strains (some of which you can actually supplement!).

 

So, we've looked at the brain, neurotransmitter, immune system, and gut bacteria.

 

One last (powerful) stop.

What is the hormonal mechanism for anxiety 

Hormones are incredibly powerful to all aspects of  the body and brain.

 

Anxiety is no different.

 

Just check out our comprehensive review of the precursor to all sex hormones, Pregnenolone.

 

From there, we drill only a bit into testosterone, estradiol, and progesterone.

 

There's a cascade effect on critical levers we looked at above.

 

For example, a key byproduct is pregnenolone sulfate...

 

It's effects on neurotransmitters are far and wide: 

Pregnenolone sulfate also has significant regulatory effects on the release of many important neurotransmitters, such as glutamate, GABA, acetylcholine, norepinephrine, and dopamine. 

https://www.sciencedirect.com/topics/medicine-and-dentistry/pregnenolone-sulfate

 

Don't get us started on estradiol and its relationship with key neurotransmitters.

 

Estradiol is especially nurturing towards serotonin – it stimulates TRPH expression to ensure that enough serotonin is made and suppresses MAO A levels to prolong the longevity of the neurotransmitter.  

https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression/ 


Look...the key takeaway is this...pregnenolone levels drop about 75% from our peak to age 70.

 

This gets to anxiety for the elderly and over time.

 

Check out the review of pregnenolone and we're working on a full review of estradiol and progesterone as well.

 

We've touch based a bit on the medications...let's look closer at the anti-anxiety medication mechanisms.

Finally...what is the mechanism for anti-anxiety medications 

We have comprehensive reviews of how the two main classes of anti anxiety medications work at our CBD versus anti anxiety medications.

 

There's also a deeper review at CBD versus benzos for GABA and CBD versus SSRI's for serotonin.

 

Those titles give it all away!

 

Benzos, generally the first line medication for anxiety, boosts GABA, our brain's brake pedal.

 

It also boosts dopamine and dopamine sensitivity which is why they are so addictive.

 

They won't do anything for the core mechanisms of anxiety that we mentioned above.

 

Just increase GABA.

 

You take away the benzo, GABA drops, and anxiety comes back.

 

It might come back even stronger since the body "normalizes" and actually drops GABA further to offset the drug's effect.

 

This and the dopamine effect is partially why it can be brutal to come off of benzos and they're generally only prescribed for short periods of time.

 

Check out how I used CBD to get off benzos here.

 

Then there are SSRI's.

 

They boost levels of serotonin primarily.

 

This may or may not help with anxiety and even if it does, it takes a few weeks to kick in.

 

Doctors usually prescribe benzos during this few weeks as anxiety can actually go UP!

 

Seem counter-intuitive?

 

Learn all about at our CBD versus SSRI for serotonin.

 

Serotonin has its hands in many pies across the brain and body.

 

It's not surprising that the potential side effects read like a bizarre laundry list of mishaps.

 

Research is pointing to one particular pie that appears to actually drive it's anti-anxiety (more so for depression) effect.

 

Serotonin and neurogenesis!

 

In fact, when researchers blocked CB1 receptors (the main endocannabinoid receptor in the brain), the neurogenesis effect from SSRI's went away.

 

So did the antianxiety effect!

 

Read that last part over.

 

The system that CBD bolsters is the KEY to how SSRI's have their core positive effect.

 

Check out CBD versus SSRi for serotonin to really be blown away.

 

Again, SSRI's don't have a dopamine addiction quality but that doesn't mean they're easy to stop.

 

In fact, doctors will warn you not to come off of them quickly.

 

You're messing with a pretty significant apple cart when you boost serotonin in one direction.

 

We wrote all about it in our CBD to wean off SSRI and serotonin syndrome.

 

So...GABA and Serotonin.

 

One pathway is to slow down brain activity.  The other is to boost repair.

 

What does CBD do for the various anxiety mechanisms above?

What is CBD's mechanism for anxiety

We're going to give the highlights and then point to much more detailed research on each section.

 

First, a refresher:

  • CBD and the brain area mechanism of anxiety
  • CBD and neurotransmitter mechanism of anxiety
  • CBD and the stress or inflammation mechanism of anxiety
  • CBD and gut microbiome mechanism of anxiety
  • CBD and the hormonal mechanism of anxiety

 

We'll start with brain area.

 

We've covered quite a bit of this at our CBD and anxiety benefits or CBD and general anxiety disorder.

 

There are two aspects to look at.

 

  • One is whether CBD can actually affect brain area connectivity and activity
  • Second is whether CBD can help repair or prevent the various insults we discussed above

 

The first really seems like a stretch.

 

How could CBD possible affect something as complicated and marbleized as brain area function??  Can it?

 

Yes!

 

A study took brain scans of people given CBD for anxiety.

 

They found very different and reduced brain activity as a result in specific areas of the anxiety circuit: 

These included a medial temporal cluster encompassing the left amygdala-hippocampal complex, extending into the hypothalamus, and a second cluster in the left posterior cingulate gyrus. 

https://www.ncbi.nlm.nih.gov/pubmed/14583744

 

Did you catch that?  

 

The amygdala (our fear center) and hippocampus (vulnerable to damage from stress).

 

The end result in that study…

 

CBD significantly decreased subjective anxiety and increased mental sedation, while placebo did not induce significant changes. 

 

Probably our favorite study deals with CBD normalizing brain activity for psychosis and schizophrenia.

 

You don't get more complicated than brain activity and psychosis!

 

This is really a departure from just pumping up GABA and serotonin as schizophrenia is known to have multiple mechanisms across a range of different pathways.

 

This speaks to the power of the underlying endocannabinoid system which is tasked with balancing key systems: 

  • Nervous system (neurotransmitters)
  • Immune system (microglia, cytokines, and more)
  • Endocrine system (hormones)

 

Check out the CBD and schizophrenia page for a full and fascinating review here: 

https://howcbdworks.net/how-does-CBD-work-for-psychosis-schizophrenia.html

 

We also go into brain areas tied anxiety in our CBD teenage anxiety since that's when these areas are developing.

 

Next up, CBD and neurotransmitters.

CBD and neurotransmitter mechanism of anxiety 

We discussed GABA and serotonin already since the common anti-anxiety medications both operate on those pathways.

 

What does CBD do there?

 

First GABA since it has an immediate effect.

 

CBD was shown to directly increase the GABA potential in neurons: 

The maximal level of enhancement seen with either CBD or 2-AG were on α2-containing GABAA receptor subtypes, with approximately a 4-fold enhancement of the GABA


https://www.ncbi.nlm.nih.gov/pubmed/28249817

 

By up to 4 times!

 

This "potential" is important as opposed to benzos which just increase GABA levels.

 

If you just keep ramping up GABA like benzos, you go through a series of responses: 

  • Calm
  • Drowsy
  • Sedated
  • Amnesiac
  • Anaesthetic
  • Dead!!

 

Meaning, you can keep ramping down brain activity till it stops.

 

That's the overdose.

 

CBD works on the endocannabinoid system which is tasked with homeostasis or balancing.

 

There isn't a reported incident of overdose with CBD with tests up to 1500 mg and even grams!

 

If GABA levels are low, it boosts.

 

If GABA levels are high, it doesn't just increase GABA levels along the same trajectory as benzos or barbiturates (even more precarious).

 

"Potential" GABA is like a reserve if needed.

 

What about serotonin?

 

You can see from our CBD versus SSRI's for serotonin that too much serotonin can be deadly!

 

There's a range of effect of CBD on serotonin: 

The acute effects of CBD clearly depend on facilitation of serotonin 5HT1A receptor-mediated neurotransmission in defense-related areas  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161644/

 

To simplify, CBD affects the "receptiveness" of neurons to serotonin.

 

Keep in mind that the brain has checks and balances to always find balance.

 

One study compared CBD versus a well known SSRI Fluoxetine (Prozac) head to head: 

Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST. 

 

More importantly, they were able to block the anti-depressive effects of both with a know serotonin blocker.

 

However, only PCPA treatment abolished CBD-induced behavioral effects in FST, indicating the participation of serotonergic mechanisms. None of the treatments induced locomotor effects. 

https://www.ncbi.nlm.nih.gov/pubmed/29885468

 

Interestingly, CBD doesn't have the initial 2-3 week boost of anxiety that SSRI's have.

 

Again, it's about "modulating" and not "boosting".

 

Check out CBD and serotonin for more detail.

 

These are just two players.

 

BDNF is another key actor for brain repair.

 

It's intimately tied with GABA activity as we get older for an anxiety mechanism: 

Reduction of BDNF results in GABAergic neuroplasticity dysfunction and contributes to late-life anxiety disorder. 

https://www.ncbi.nlm.nih.gov/pubmed/30714802

 

What does CBD do for BDNF?

The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus (HPC).  

https://www.ncbi.nlm.nih.gov/pubmed/29869197

 

The really cool part about that study...is where this occurred.

 

The prefrontal cortex is a key player in the anxiety mechanism.

 

It's the rational part of brain that puts a check on all the fearful chatter from the amygdala!

 

The hippocampus is that part of our brain that literally shrinks from acute and chronic stress!

 

See CBD for hippocampus neurogenesis.

 

Speaking of stress and inflammation.

CBD and the stress or inflammation mechanism of anxiety 

Let's look at just two players that are known to wreak havoc on our brain from stress, inflammation, and even infection.

 

Cortisol and Microglia.

 

One stress.  One immune responder.

 

First cortisol...what can CBD do there?

 

Another crossover study showed that plasma cortisol levels decreased more significantly when given oral CBD, 300 to 600 mg 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/

 

That's actually from a sleep study since cortisol is key to our sleep/wake cycle (with GABA being the sleep part of the equation).

 

Check out CBD and cortisol for anxiety to learn why this is so important.

 

Let's go further up the scale to corticotropin releasing hormone.

 

You probably haven't heard of this beauty but it starts the cascade of stress response to the body from the brain.

 

Too much of this hormone has actually been shown to increase the amygdala size (our fear and anxiety center).

 

What does CBD do there?

 

Follow us on this.

 

CBD increases Anandamide (our naturally occuring "bliss" chemical in the brain: 

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/

 

And what does anandamide do to for corticotropin releasing factor? 

Interestingly, cannabidiol at low (5 mg/kg) and intermediate doses (15 mg/kg) successfully blocked the effects induced by acute stress on corticotropin-releasing factor, pro-opiomelanocortin and glucocorticoid receptor gene expression. 


https://journals.sagepub.com/doi/abs/10.1177/0269881118805495?journalCode=jopa

 

Check out CBD for corticotropin releasing factor here to get full scoop for this stress response mechanism.

 

Finally, there's the microglia and neuroinflammation mechanism.

 

We have an entire article on CBD, microglia, and neuroinflammation but a quick example that's incredibly important as cannabis is legalized across the US.

 

Interestingly, THC was shown to dysregulate microglia activity which CBD helped to offset. 

In pilot experiments we have replicated the finding that adolescent, low-dose THC activates microglia in the prefrontal cortex via CB1 cannabinoid receptors and increases IL-6 mRNA. The increase in IL- 6 was prevented by concurrent cannabidiol.  

http://grantome.com/grant/NIH/R21-DA039463-02

 

Let's walk through this.  

 

THC caused microglia to over-react in the very part of the brain that tasked with countering our runaway fears (from the amygdala).

 

Incidentally, new research is showing this same effect in schizophrenia.

 

The last part is amazing.

 

CBD (cannabidiol) prevented the inflammatory agent created by this activation, IL-6.

 

That's just one example from our review which you have to check it out.  

 

It truly is cutting edge research on how THC, CBD, the brain work.

 

Let's travel back down south to the gut.

CBD and gut microbiome mechanism of anxiety 

This may be one of the most powerful effects of CBD.

 

As we saw above with microglia in the brain, CBD has a powerful anti-inflammatory effect across the body.

 

A great deal of inflammation starts in the gut and spreads from there.

 

Literally.

 

The gut has a barrier just like the brain does.

 

If it weakens, bad actors from our gut can escape across and travel to other parts of the body including the brain.

 

Can CBD help with this so-called "gut permeability"? 

cannabidiol accelerated the recovery from cytokine-induced increased permeability; an effect sensitive to CB1 receptor antagonism. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423254/

 

Let's see why this is important.

 

First, the gut bacteria actually produce many important chemicals including neurotransmitters we discussed above.

 

90% of your serotonin is made in the gut!

 

Working with healthy adult mice, the researchers showed that disrupting the normal bacterial content of the gut with antibiotics produced changes in behaviour; the mice became less cautious or anxious.  

https://fhs.mcmaster.ca/main/news/news_2011/gut_anxiety_link_study.html

 

When they removed the antibiotics, normal behavior returned.

Then there are the bad bacteria.

 

There's a known tie between bad pathogens such as Claudimum difficile (C.diff) and mental health issues including anxiety.

 

This is the antibiotic resistance bacteria in hospitals that's spreading.

 

It's the ultimate test for gut permeability.

 

What can CBD do there?

Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721977/

 

It's amazing this isn't front page for us since the all the scary news on C.diff has already made the rounds.

 

Check out CBD and probiotics for anxiety or CBD and the microbiome to really learn more about this gut and anxiety mechanism.

 

One more stop.

CBD and the hormonal mechanism of anxiety 

Hormones always get complicated.

 

Fast!

 

They are so powerful and interconnected across almost every system in your body.

 

We know that the endocannabinoid system is highly integrated with hormones: 

It appears to play a very important regulatory role in the secretion of hormones related to reproductive functions and response to stress.  

https://www.ncbi.nlm.nih.gov/pubmed/17369778

 

That corticotropin releasing factor above is such a stress hormone!

 

We know that CBD directly calms down its expression as a means to reducing anxiety.

 

Just to see how complicated and interwoven endocannabinoids and hormones can be, let's look at a wonderful review here: 

http://www.felicelgershmd.com/the-endocannabinoid-system-and-estrogen/

 

Estradiol is one of the three main flavors of estrogen.

 

It's known to have a powerful antianxiety and antidepressant effect.

 

It's also dropping as we get older and falls through the floor at perimenopause (see my experience here).

 

Interestingly, research is showing that it has this effect by increasing anandamide and reducing FAAH (two endocannabinoids).

 

We talked about anandamide up above (our "bliss" molecule).  FAAH is the chemical that breaks it down.

 

It's fascinating as we covered its effect on anxiety in our review of the woman who unable to feel pain or anxiety here.

 

Here's the important part. 

Further confirming these findings are studies showing that when a CB1 receptor antagonist was given to rats, the anxiolytic effect of estradiol was blocked, and when a blocker of FAAH (the enzyme which degrades anandamide) was given, and levels of the endocannabinoid rose, and an anxiolytic effect occurred, precisely like that produced by estradiol.

 

Let's decipher that please.

 

Estradiol matched the effects of reducing anxiety the same as blocking FAAH (like the woman who can't feel anxiety). 

 

This is about as succinct an example we can give on how endocannabinoids and hormones interplay.

 

Why is this important for CBD?

 

CBD boosts anandamide and reduces FAAH!!! 

Biochemical studies indicate that cannabidiol may enhance endogenous anandamide signaling indirectly, by inhibiting the intracellular degradation of anandamide catalyzed by the enzyme fatty acid amide hydrolase (FAAH). 

http://www.felicelgershmd.com/the-endocannabinoid-system-and-estrogen/

 

Check out the pregnenolone and CBD article since the cascade of many hormones start there.

 

Also… 

  • CBD and weight and obesity (hormones that govern energy and fat)
  • CBD and monthly cycles (ummm...hormones)
  • CBD for perimenopause (drop in key hormones)

 

Let's look at practical questions.

How much CBD for the anxiety mechanism based on research 

Here's where we can get technical.

 

We've looked at two various angles of anxiety:

  • Mechanism by which damage occurs leading to anxiety (stress, trauma, infection, etc)
  • Mechanism by which damage is repaired for anxiety (neurogenesis, serotonin, hormones)

 

The first really depends on your system, genes, and past!

 

Generally, people feel an immediate effect from 50-200 mg of CBD.

 

It's best to start low at about 25 mg to test your system.

 

Keep in mind that some of the studies went as high as 600 mg (CBD and public speaking for example).

 

The second item is more interesting.

 

Neurogenesis was shown to operate on a bell curve with CBD.

 

It would peak at about 300 mg and drop from 300 to 600mg even though the anxiety response would increase.

 

Ideally, we don't go higher than 300 mg for this reason.  

 

Check out how many mg of CBD for anxiety for more detail here.

What's the best CBD for the anxiety mechanism 

Beyond the basics: 

  • Organically grown in the US (can't buy from Amazon folks)
  • CO2 processed
  • 3rd party tested free of:
  • NO THC (see CBD versus THC for anxiety to understand why)
  • NO Pesticides
  • NO Heavy Metals
  • NO Mold
  • NO Bacteria

 

Those are the basics.

 

Then there are nuances brought out by research.

 

First, the whole full spectrum versus CBD isolate question for anxiety.

 

We described above how GABA is a critical level for anxiety.

 

Histamine is incredibly excitatory and actually eats up GABA.

 

We don't want a histamine response due to all the plant material in full spectrum CBD.

 

40-60% of the population has a histamine issue.

 

This only gets worse as we get older and for women.

 

Roughly 70% of those people are allergic to THC.

 

The problem is that many companies are pushing full spectrum out there.

 

Most!

 

That's why we come across so many people who have bad reactions at first to CBD.

 

We did.

 

That (and the 100's of NIH studies we've read) also drive why we focus on CBD isolate.

 

We crafted IndigoNaturals based on research so hopefully you can benefit the most.

1000 mg cbd isolate for anxiety2000 mg of cbd isolate for anxiety

6000 mg of cbd isolate for anxiety

 

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