CBD and Anxiety - The Ridiculous Guide

  

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.

1 - GABA - the immediate hammer for anxiety

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.

2 - Serotonin - the longer term player for anxiety

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.

3 - Steroids - the anti-anxiety players

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.

4 - The Sublingual Trick

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!

5 - Exhausted serotonin after pain (physical or psychological)

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:

repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.

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:

• Reduced anxiety (ding ding ding)
• "Rescued" serotonin function (5HT)
• Improved pain sensitivity

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

6 - CBD versus THC for anxiety

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.

7 - Early trauma/infection and anxiety

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:

• Downregulate GABA, serotonin, and others
• Upregulate stress hormones, inflammation, glutamate (HUGE player)

We'll be talking about all of these below since this is CBD's wheelhouse.

Let's check that house out now.

8 - CBD and anandamide

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:

• Nervous system - GABA, serotonin, glutamate, etc
• Endocrine system - hormones including steroidal and metabolic
• Immune system - inflammation and cellular birth/death cycles

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!

9 - Full spectrum versus CBD isolate for anxiety

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!

10 - Anxiety and CBD Study #1

The above is all well and good but what about studies on people?

Okay tough guy!

Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration.

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).

11 - How much CBD for anxiety?

• The low level is generally around 20-50 mg daily.
• Sleep studies (also GABA) around 150 mg daily
• Trait or more serious anxiety around 300 mg daily

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!

12 - Due South! The gut and anxiety

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:

Here, we showed that mice with low levels of fecal Akkermansia spp. exhibited decreased center time during the open field test, which is indicative of increased anxiety-like behavior,

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.

13 - One of our favorites - CBD and Public Speaking

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:

Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech.

Interesting Items:

• Single-dose of 600 mg 1 hour prior to simulated public speaking
• One group of participants had been diagnosed with social anxiety disorder
• 24 participants
• Double-blind, Placebo

Big mic-drop moment:

The SSPS-N scores evidenced significant increases during the testing of a placebo group that was almost abolished in the CBD group.

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.

14 - Take CBD after Food

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.

15 - BDNF, your new best friends

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):

• Stress
• Trauma
• Infection
• Hyperactive immune (the early trauma/infection piece)
• Glutamate (from the hyperactive immune)
• Drugs/meds
• Poor sleep
• Loss of steroids

And on this side:

• BDNF!
• Serotonin (which drives BDNF)
• Anandamide (which supports BDNF)

So…BDNF!

Yes…it's that big of a player and we'll cover it in detail.

As for anxiety??

16 - BDNF and Anxiety Study #1

These findings indicate that longer periods of maternal separation are necessary to increase anxiety-like behavior, elevate CORT levels, and further suppress BDNF levels in the PFC, providing a possible mechanism to explain why more severe forms of ELS lead to more significant psychiatric and medical consequences later in life.

https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00709/full

2020 paper. Lots of goodies here.

• ELS is early life stress (remember the trauma/infection piece!!)
• Higher stress (CORT)
• Higher anxiety
• Lower BDNF in the prefrontal cortex, just the rational seat of the brain that keeps our fear center under check.

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:

• CBD calms cortisol (see CBD and stress)
• CBD supports BDNF (see CBD and BDNF)
• CBD calms immune hyperactivation (see CBD and neuroinflammation)

So…good stuff? Make a checkmark by BDNF.

17 - Magnesium glycinate - the mineral "CBD"

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:

mild deficiency can remain undetected as it often occurs with nonspecific symptoms such as irritability, nervousness, mild anxiety, muscle contractions, weakness, fatigue, and digestive troubles

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).

18 - The Anxiety "Circuit" in the Brain

We need an introduction since the players are going to keep cropping up.

You could say there are two brains in your head:

• The "modern" brain (behind the forehead and outer layer) with the prefrontal cortex - our "rational" player
• The "reptilian" brain (inner and back) with the amygdala/hippocampus - our "emotional" player including…fear

Don't glaze over…we'll walk you through it.

The snapshot:

• Our prefrontal cortex keeps a check on our "animal spirits" including fear
• The prefrontal cortex is vulnerable to damage (glutamate, drugs, stress, etc)

.

 

 

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?

19 - CBD Study on the prefrontal cortex

In the prefrontal cortex, the area of the brain used for planning and decision making, CBD caused a significant increase in blood flow in the orbitofrontal cortex.

https://www.technologynetworks.com/neuroscience/news/cannabidiol-significantly-improves-blood-flow-to-brains-hippocampus-new-findings-show-338619

Okay, and what about brain repair?

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex

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.

20 - CBD versus benzos

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:

• Come on fast
• Last a shorter period of time
• Fall off a ledge in levels

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!

21 CBD and cortisol

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!

Increased levels of cortisol following induction of the stress response stimulates the production of 2-AG in the hypothalamus and other stress centers of the brain, increasing CB1 signaling. This applies negative-feedback inhibition of the HPA axis and can facilitate termination of the stress response

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!

CBD's effect directly in this hocus pocus:

CBD treatment attenuated the abnormal cortisol response and reduced the acute stress-associated increase in anxiety, as measured by the STAI

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.

22 - the THC anxiety connection

In that same study above, they looked at THC and stress specifically.

The results:

THC is known to induce stress in healthy people as demonstrated by an increase in cortisol and transient anxiety-like behavior in people with no anxiety disorders

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.

23 - How often to take CBD?

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…

24 - can you take CBD in the middle of the day?

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.

25 - CBD and histamine for anxiety

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)?

altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control.

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.

26 - CBD versus SSRIs for anxiety

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

27 - CBD Study #2 - Direct DNA management

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:

using a rodent model of brain iron loading, CBD normalized the methylation levels of mitochondrial DNA in the hippocampus

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)

28 - Vitamin D - The Steroid from the Sun

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)

A study looked at Vitamin D supplementation and anxiety with a 2.4 point drop in the HAMA score (measure of anxiety).

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:

A 1 ng/mL lower 25[OH]D was associated with 0.043 and 0.040 higher DASS-21 Anxiety and PHQ-9 Scores (p-values=0.052 and 0.029, respectively).

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.

29 - CBD and Fear Extinction

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:

Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression.

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.

30 - Can you get rebound anxiety from CBD?

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:

• Benzos - brutal GABA tolerance…and addiction
• SSRIs - tolerance with our most powerful neurotransmitter out there
• Alcohol - GABA and serotonin tolerance
• Antihistamines - hence the sluggish, brain-foggy feel
• Gabapentins and other synthetic GABA agents
• Various supplements from SAMe, 5HTP, and herbs

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

31 - CBD and Negative Thoughts

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.

This is a systemwide "setting" in the brain where you usually daydream, think about the future, ruminate on the past, etc.

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!

If CBD can restore disruption to the salience network, this could be a neuroprotective mechanism to explain its potential to treat disorders of salience such as psychosis and addiction,”

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.

32 - The First 30 Days

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.

33 - Study #2 - CBD and fearful faces

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:

Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdala and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations

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!

34 - What Does CBD Feel Like for Anxiety?

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

35 - Does CBD Work Immediately?

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.

36 - Glycine - GABAs calming cousin

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
• Glutamate
• Cystiene

 

 

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!

CBD exerts a positive allosteric modulation of α3 glycine receptors (pooled EC50 = 11.0 μM, n = 3 studies

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)

37 - NAC, CBD's partner in criminal calming

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!

N-acetylcysteine was found to be superior to placebo in reducing anxiety symptoms in secondary outcome analysis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217900/

We have a monster review of NAC for mental health but the detox piece alone is critical.

38 - Can you buy CBD on Amazon

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.

39 - Can you take CBD daily?

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:

• SSRIs - tolerance
• Benzos - brutal tolerance and nasty addiction (fast - 2 weeks)
• Alcohol - tolerance and addiction longer term
• Gabapentin and synthetics - tolerance
• Antihistamines - Benadryls, etc - hence the rebound and they rip acetylcholine, your nervous system calming agent longer term

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.

40 - The Achilles Heal of SSRIs

An interesting study genetically blocked CB1 receptors. This is where CBD and other cannabinoids do their work in the nervous system.

Moreover, CB1 knockout mice displayed functional impairment of 5-HT1A and 5-HT2A/C receptor-mediated neurotransmission in the hippocampus [117] while a loss of antidepressants behavioral effects were described after genetic blocked of CB1 receptors

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.

41 - The "Rest and Digest" system for anxiety

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.

 

Some of this is due to our background systems being janky.

 

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??

These findings demonstrate that CBD can normalise muscarinic neurotransmission imbalances in male poly I:C offspring in regions of the brain implicated in cognition.

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!

42 - CBD and Stress - the first shoe to drop

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!

CBD also acts to reduce stress and its manifestations by non-endocannabinoid receptors (Figure 3). Even at low doses, CBD acts as an agonist at serotoninergic 5-HT1A receptors and blocks stress-induced changes in 5-HT1A receptor gene expression, which reduces anxiety associated with the stress response

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…

43 - CBD and stress response in high risk individuals

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:

Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p’s < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change.

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….

44 -Early life stress and anxiety later

We have to unwrite the effects of trauma, stress, and infection from early on.

Or we're just spinning our wheels.

To point:

We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood

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:

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

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.

 

See CBD and trauma or why the immune system is the future of mental health.


Okay…let's come up for air!

 

45 - Can CBD help you last longer?

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….

46 - what does CBD taste like?

It depends on the product as some can be downright wheatgrassy (hemp oil base).

Our CBD isolate has just two ingredients:

• CBD isolate
• MCT oil from organic coconut oil

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.

47 - CBD and Brain Inflammation for Anxiety

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:

Higher levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-8) would be associated with more severe psychiatric symptoms (i.e., level of depression, stress and anxiety).

https://www.sciencedirect.com/science/article/pii/S2666354620300107

Okay….and CBD's effect?

The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.

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.

48 - What about CBD versus Benzos?

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.

49 - CBD Study - Why People Use CBD?

Big shocker…look at the results were why people continue to use CBD:

Respondents reported that CBD use was effective for stress, sleep problems, and anxiety in those who used the drug for those conditions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893882/

This really points to stress related issues!

Cortisol eats up GABA (and magnesium).

• Sleep - yes, GABA is the main manager
• Anxiety - yes, GABA is the "now" player for anxiety
• Stress - well…yes!

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:

• CBD and serotonin
• CBD and GABA
• CBD and endocannabinoid system (anandamide)

Speaking of stress

50 - CBD and CRF connection

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?

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://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.

51 - The woman who can't feel anxiety (or pain or depression)

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.

52 - Is CBD legal?

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.

53 - CBD Study # 4 - 2021 review of results

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:

• Participants experienced a 71% improvement in their well-being, on average
• 63% experienced a clinically meaningful improvement in anxiety
• 61% experienced a clinically meaningful improvement in sleep quality
• 47% experienced a clinically meaningful improvement in pain
• 61% reported an effect within one to four hours of taking their product

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?

54 - Friends of CBD - Medicinal Mushrooms

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??

The results showed that the methanol extract of G. lucidum at a dose of 200 mg/kg, administered orally, shows a significant increase in the average time spent in the open arms of the EPM when compared with the control; this was comparable to the effect of the standard drug (diazepam, 2 mg/kg by mouth).

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.

55 - Can you overdose on CBD?

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.

• Calm
• Sedated
• Hypnotic
• Amnesiatic
• Anaesthetic
• Catatonic
• Dead

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.

56 - CBD and oxidative stress for anxiety

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:

Studies conducted over the past few years suggest that anxiety disorders may be characterised by lowered antioxidant defences and increased oxidative damage to proteins, lipids, and nucleic acids. 

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??

CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C

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!

57 - CBD and phobia

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?

The evidence indicates that cannabidiol reduces learned fear in different ways: (1) cannabidiol decreases fear expression acutely, (2) cannabidiol disrupts memory reconsolidation, leading to sustained fear attenuation upon memory retrieval, and (3) cannabidiol enhances extinction, the psychological process by which exposure therapy inhibits learned fear.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121237/

Let's break that down…it's too cool!

• CBD directly reduces the feeling of fear
• CBD breaks the cue-anxiety cycle
• CBD slowly reduces the "learned" fear process in the brain

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.

58 - CBD versus gabapentin and synthetic GABA's

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:

Gabapentin loses efficacy over time after nerve injury in rats: Role of glutamate transporter-1 in the locus coeruleus

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.

59 - How fast does CBD work for anxiety

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

60 - CBD and acetylcholine - our calm and focused player

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:

We found CBD exhibited direct excitatory effects on vagal afferent neurons that required TRPA1, were augmented by TRPV1

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.

61 - the CBD trick with steroids

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:

Interestingly, however, anxiolytic- and antidepressant-like effects produced by estradiol administration are attenuated by CB1R blockade [112], whereas estradiol administration increases AEA levels

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!

62 - CBD and social anxiety

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:

Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001),

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:

These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

 

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!

63 - CBD to taper off benzos

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:

• CBD supports GABA when low.
• CBD support glycine which keeps glutamate in check
• CBD helps to balance dopamine (see study on schizophrenia)
• CBD supports neurogenesis to "overwrite" the learned addiction pathways that dopamine carved out

There are other supporting tools as well at our top 10 tip guide.

63 - CBD and the amygdada (our fear hub)

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:

In healthy volunteers treated with CBD and submitted to a model of the presentation of fearful faces, a decreasing of the amygdala and anterior and posterior cingulate cortex activities and a disruption in the connections between the amygdala and the anterior cingulated cortex were observed

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:

Acute effects of CBD reduce DRN-amygdala excitatory signaling to lessen the activity disparity between amygdala and mPFC.

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.

64 - What does CBD feel like for anxiety

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.

65 - CBD versus alcohol

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!

• GABA
• Serotonin
• Glutamate
• Adrenaline even!

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!

66 - Will you fail a drug test with ls CBD

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).

67 - Does CBD build tolerance longer term?

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.

68 - CBD and stress reserve

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:

• Magnesium
• GABA
• Serotonin
• Anandamide

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:

Even at low doses, CBD acts as an agonist at serotoninergic 5-HT1A receptors and blocks stress-induced changes in 5-HT1A receptor gene expression, which reduces anxiety associated with the stress response

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):

AEA may function as a mediator of ‘emotional homeostasis' (Haller et al, 2013; Marco and Viveros, 2009), functioning to keep anxiety at bay in resting conditions, from which disruption of this signal by stress could contribute to the generation of an anxious state

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).

69 - Can you take CBD with meds?

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.

70 - CBD and the genes of anxiety

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:

These preliminary findings raise the possibility that the observed anxiolytic effects of CBD may rely on the action of DNMTs that restore DNA methylation levels at aberrantly regulated genes contributing to anxiety disorders.

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!

71 - Why we feel stressed when sick (hello tryptophan)

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:

• More aches and paines
• Lower mood and energy
• Less stress resilience
• More anxiety
• Poorer sleep

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.

72 - CBD  to taper off SSRIs

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.

73 - The GABA quirk for autism

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:

Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant.

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.

74 - Will CBD make you feel "high"

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.

75 - The PPAR connection for anxiety

PPAR is a fascinating pathway. A key manager of inflammation in the body and brain.

For anxiety, it's all about stress response:

PPAR–α activation has been shown as a natural response to stress, having the ability to mediate and modulate the 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?

cannabidiol (CBD), abnormal CBD, cannabigerol, cannabigerol quinine, cannabichrome and ajulemic acid (a synthetic analogue of a tetrahydrocannabinol metabolite, AJA) can all bind to, increase the transcriptional activity of and exert effects that are inhibited by selective antagonists of PPARγ

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.

76 - Hemp oil versus CBD isolate 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.

77 - Do you need THC to activate CBD for anxiety

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.

78 - Best CBD for anxiety

Three key aspects to getting the most out of CBD and all the research you read above (you poor soul!

• Quality of CBD
• Type of CBD
• Cost of CBD

First, we have to make sure it's a good product.

The basics:

• From organically grown hemp in the US at FDA registered farms
• 3rd party tested
• CO2 cold-processed
• No THC
• No pesticides
• No solvents
• No heavy metals
• No mold
• No bacteria

 

 

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).

79 - Is CBD addictive

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.

80 - CBD and brain white matter

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:

Non-clinical individuals with high anxiety already have white matter alterations in the thalamus-cortical circuit and some emotion-related areas that were widely reported in anxiety-related disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117387/

Remember how we said that CBD is not the same thing as THC?

THC strongly disrupts striato-cortical networks, but this effect is mitigated by co-administration of CBD in the limbic striatum network.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150138/

Brain highways. White matter!  One more issue with THC.

81 - The social anxiety connection

A study looked at 18-19 year old Japanese students with social anxiety disorder diagnosis for two important tests of social anxiety.

The results:

SAD symptoms were measured at the beginning and end of the treatment period using the Fear of Negative Evaluation Questionnaire and the Liebowitz Social Anxiety Scale. CBD significantly decreased anxiety measured by both scales.

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

82 - CBD and glutathione, our primary detox system

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.

 

What about Glu and anxiety?

 

They can literally see on a sliding scale the reflection of anxiety states by glutathione metabolites in urine:

We found that normal anxiety state values corresponded to low urine redox potentials, whereas higher anxiety states were associated with high urinary redox potential.

https://www.hindawi.com/journals/omcl/2014/430216/


What about CBD and glutathione?

Thought you would never ask..

Repeated doses of CBD in inflammatory conditions were found to increase the activity of glutathione peroxidase and reductase, resulting in a decrease in malonaldehyde (MDA) levels, which were six times higher in untreated controls

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!

83 - CBD study for young people with anxiety

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:

OASIS scores decreased from 10.8 (3.8) at baseline to 6.3 (4.5) at week 12, corresponding to a -42.6% reduction

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.

84 - benzo's and brain waves (not what you would expect)

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:

While a decrease in high frequency EEG activity is associated with a decrease in arousal in drug-free conditions, sedative benzodiazepines increase beta activity

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??

85 - top 10 tips to get off benzos with CBD

Big review on top 10 tips to get off benzos but just the headlines:

• Go slow (very slow) on the wean - timetable below
• Tool #1 magnesium glycinate - supports GABA
• Tool #2 CBD isolate - feedback mechanism for GABA, serotonin, and more
• Tool #3 NAC - keeps excess glutamate at bay
• The Pillcutter is your best friend
• Daily timing
• The first 10 days versus the back 20
• Addressing why GABA was down to begin with
• Steroidal hormones are critical
• Focus on the immune system and erase early trauma/infection
• Learn about each one here.

It's the new Opioid crisis in the making!

More detail on each benzo taper tip.

86 - will CBD make you lazy

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.

87 - CBD marching orders for stressful situations

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:

• GABA
• Magnesium
• Serotonin
• Anandamide

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.

88 - Can CBD affect blood tests

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.

89 - Is there an age requirement for cbd

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.

90 - What's the best ratio for CBD to THC

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.

91 - An anecdotal case of CBD for girl following abuse

This is a horrible story. Significant abuse at an early age. Medications were not working.

CBD's effect:

A trial of cannabidiol oil resulted in a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient’s sleep.

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..

a crossover trial comparing CBD (40, 80, and 160 mg) with placebo and nitrazepam (5 mg) among 15 insomniac volunteers revealed that duration of sleep significantly increased following administration of the high-dose CBD (160 mg)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763649

More on sleep below.

92 - CBD versus 5HTP, l-theanine, SAMe, etc

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:

• Supplements that boost serotonin (SAMe, 5HTP, etc)
• Supplements that boost GABA (l-theanine, valerian root, etc)
• Supplements that affect steroidal hormones (ashwaghanda, black cohash, etc)

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:

• The other big issue is histamine response (I know…broken record).
• Many "natural" supplements can cause a histamine response which…feels like anxiety!

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.

93 - Studies on CBD and autism anxiety

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:

Considerable improvement in behavioral problems was noticed in 61% of patients. Improvement in anxiety and communication problems was seen in 39 and 47%, respectively.

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/

94 - Sleep benefits- the 2-fer for anxiety

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:

• GABA manages both sleep and clam
• Cortisol (stress hormone) is involved in both
• Histamine - drives insomnia as well as anxiety when excessive
• Inflammation is the enemy of both

We have a huge review of CBD and sleep but a big study shows the cross-over:

Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%)

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

CBD was well tolerated.

Many more studies at the link above.

95 - Can teens and children use CBD for anxiety

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:

• Effects on development
• Effects on steroidal hormones
• Tolerance, addiction, and cognitive function

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

96 - The hippocampus - our very vulnerable mood switch

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!!

Preclinical studies have shown CBD to induce synaptic plasticity and facilitate hippocampal neurogenesis,29,30 with some evidence suggesting that the proneurogenic action of CBD via the hippocampus may underlie its anxiolytic effects

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.

97 - CBD and cognitive function (thinking clearly)

A lot has to go right for our brains to work correctly.

For clear thought (opposite of brain fog), we need the following:

• Serotonin in good range
• Acetylcholine (calm an focused) humming
• Low cortisol (stress) and inflammation
• Good balance of glutamate (gas pedal) and GABA (brake pedal)

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:

Recent reviews suggest that CBD has no effect on cognition in healthy individuals, but can improve cognitive processes including attention, executive function, working memory, and episodic memory in various pathological conditions including acute THC intoxication

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…

acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance.

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).

98 - Does CBD affect estrogen or testosterone

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.

Men's testosterone has dropped significantly across every age band during the last 20 years!

 

Can't stress how important these pathways are to anxiety and health in general. Learn more about steroids and longevity.

99 - CBD versus CBN, CBG, CBC, etc

There's a mad rush to push other cannabinoids as magical things.

Delta8 is the new entry to this effort.

• CBN will do this
• CBG will do that
• Delta8 is a unicorn

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!

100 - GPR55 - not another droid

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!

101 - If we had one final thing to say!!

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:

• Steroidal hormone loss
• Early trauma, stress, infection

Steroid loss is how we found CBD to begin with…a brutal perimenopause when estrogen went on a roller coaster ride. 

25% of women will have debilitating perimenopauses (mid-late 40's).  Learn why here.

• Progesterone drops 1% each year from around age 20 and by 50% at age 40
• Estrogen drops through the floor late 40's (perimenopause)

Testosterone drops 1% each year from around age 20

• P directly drives GABA, our primary calming agent (and target of benzos)
• E and T drive serotonin, our stress response buffer and repair manager (BDNF)

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:

• Reduced GABA (less calm - target for benzos)
• Reduced serotonin (lower stress response buffer - target for SSRIs)
• Reduced BDNF (less repair)
• Increased cortisol (stress)
• Increased inflammation (collateral damage in the brain)
• Increased glutamate (burns out neurons)

Goodness. Can we drop the mic now!

This early "ramp-up" can even be in-utero. In fact, the "markup" can go back 10 generations!

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:

• CBD isolate - powerful balancing agent across all the pathways above
• Medicinal mushrooms - helps to rebalance our immune system response
• Magnesium glycinate - calming agent for both nervous system and immune system
• Psilocybin - game-changing editor coming soon

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.

Related Research:

CBD and anxiety

CBD and anxiety research

CBD versus anti-anxiety meds

 

 

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.