CBD and Stress Response with a Focus on Mental Health

CBD and stress response for mental health

 

It will all make more sense as dive down the rabbit hole of stress response in the body and brain.

 

Many people ask, "Does CBD really do anything?" and rightfully so.

 

There's so much bad information and hype out there.

 

The better question is...how can CBD affect so many different pathways positively?

 

We've covered research from traumatic brain injuries to gut inflammation to schizophrenia.

 

All are intimately tied together but at the heart of everything is stress!

 

This is also the connection with CBD and how it works as we'll dig into below.

 

As a reminder of just how important stress response is, look at the two leading triggers for addiction relapse: 

 

BDNF levels (we'll cover below)

 

And

 

Stress levels!

 

compare cbd isolate options 

 

Okay, so here are the topics we'll cover: 

  • A quick introduction to the stress response system
  • Key issues tied to stress overload
  • Stress and inflammation...especially in the brain
  • How CBD works for stress response
  • CBD and CRF
  • CBD and cortisol
  • CBD and serotonin
  • CBD and GABA
  • CBD and brain inflammation (immune response)
  • Steroidal hormones and stress response
  • How much CBD to take for stress
  • What's the best CBD for stress response support

 

Let's get started.  

A quick introduction to the stress response system 

Stress isn't all bad.  In fact, it's critical to survival which is why we have it to begin with.

 

It's a very primitive system to cue your body and brain into action due to perceived danger.

 

Back in the day, this might be hunger or conflict within a tribe but now, it's more likely to be traffic or a job interview.

 

The body's systems can't distinguish between the two so we're addressing the modern world with pretty old machinery.

 

There's a cascade of neurotransmitters, immune responders, and hormones that all kick in throughout the process.

 

We'll zero in on the big players to avoid falling down the complex chemical rabbit hole.

 

We need to introduce the following: 

  • CRF - corticotrophin-releasing factors
  • Cortisol
  • Glutamate
  • Cytokines
  • Serotonin
  • GABA
  • Anandamide

 

We have 4 players that initiate and carry out our stress response (the first four) and 3 that push back.

 

Both sides are important and extreme or chronic stress reflects a mismatch of these opposing forces.

 

Let's get a quick introduction to these main players.

 

First, the stress pathway players!

 

CRF

 

This starts the ball rolling. CRF is a hormone that initiates our stress response: 

Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress.

https://pubmed.ncbi.nlm.nih.gov/16423710/

 

The party starts here so we'll want to include that in our discussion.

 

A quick side note from our review of SSRIs.  There's a strange quirk that SSRIs can actually increase anxiety and depression during the first 2 weeks.

 

The doctors will generally prescribe benzos (see CBD versus benzos) for this initial period under the excuse of "it takes the SSRI a few weeks to kick in" but that's the real reason for the benzo roll-out.

 

SSRIs boost serotonin which can actually cause more CRF release (serotonin is a master regulator of all human behavior after all with different effects throughout the brain).

 

The benzo is to camouflage this stress initiation till the other effect kicks in (see how SSRIs really work) till it doesn't due to tolerance.

 

Back to our stress story.

 

Once CRF kicks up, the henchmen kick in...cortisol!

 

Cortisol is our primary stress response agent...this is the one you feel and it doesn't walk softly!

 

The mean cortisol level was found to increase approximately 9 times in stressful periods compared with that in relaxed periods. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371989/

 

Here's the issue...cortisol does many more things than just stress!

 

It's your key "wake" chemical along with histamine.  It should spike in the morning (to wake up), slowly trail off, and recede at night.  

 

It's also intimately tied into metabolism, sugar, and more since stress was supposed to reflect times of danger and your muscles may need more energy for running from that tiger.

 

Not so much for the final exam test!

 

There's a mismatch between our 40,000-year-old blueprint and our modern life which we'll see later.


Where CFR and cortisol are very stress-specific, the foot soldier is glutamate.

 

Glutamate is our nervous system's "gas pedal".  

 

Mounting evidence suggests that acute and chronic stress, especially the stress-induced release of glucocorticoids, induces changes in glutamate neurotransmission in the prefrontal cortex and the hippocampus, thereby influencing some aspects of cognitive processing. 

https://pubmed.ncbi.nlm.nih.gov/22127301/

 

More specifically…

 

both stress and corticosterone treatment induce enhancement of activity-dependent glutamate release. 

https://www.sciencedirect.com/science/article/abs/pii/S0197018611001690

 

To boil this all down…

 

Stress causes the nervous system to light up... the "on" button is being jammed on.

 

This makes sense...with the tiger situation, you need all systems firing and indeed, glutamate is the fuel for this!

 

This brings us to our next section...the immune system and inflammation.

 

All the new exciting research on mental health and stress has been around the immune system.

 

Dementia.  Anxiety.  Depression.  Bi-Polar.  Trauma.  You name it...the immune system is front and center.

 

We think of it as just a responder to colds and flus but there's so much more to unpack there.

 

In the brain, our immune system is multi-tasking!

 

It's in charge of literally the physical construction, pruning, and repair of our brain pathways!

 

This brings back glutamate.  A big source of glutamate is our microglia, the key sentinels of the brain's immune system.

 

To wit…

 

Similarly, Fontainhas et al. [32] demonstrated that microglial process motility is significantly increased in response to ionotropic glutamatergic neurotransmission 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788324/

 

So glutamate ramps up the immune response (microglia activity) and that brings the next piece of the puzzle...inflammatory agents called cytokines...

 

The vast majority of studies have demonstrated that stress promotes significant structural remodeling of microglia, and can enhance the release of pro-inflammatory cytokines from microglia.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788324/

 

Goodness...the brain has only a few tricks and it responds to the stress of a final exam in the same way as the stress of an attacking bacteria or virus.

 

More glutamate and more inflammation (cytokines).

 

So...that's the pro-stress response players.

 

Let's look at the other side.

 

We'll start with our big stress-response buffer...serotonin.

 

Serotonin and stress

 

We have a whole review of serotonin since it is intimately tied into every mental health issue.

 

Serotonin is our first line of defense against stressors of all kinds including pain, trauma, psychological stress, and more.

 

Not only does it dictate our stress threshold but also our stress mitigation.

 

In fact, gene studies on serotonin processing genes show direct effects on our stress response: 

In this sample of newborn babies, the 5-HTTLPR genotype affected the HPA stress response to painful stimulation irrespective of additional influence of pre-or perinatal environmental factors we measured. 

https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.452.5135&rep=rep1&type=pdf

 

5HT is the scientific name for serotonin.

 

HPA is the vast hormone activation system that includes stress hormones like cortisol and CRF.

 

Interestingly, early trauma (even infection in utero, especially the 3rd trimester) can downregulate serotonin function...for life!

 

We have a whole review on unwinding the effects of trauma here.

 

Serotonin is our longer-term stress response player (see full review on serotonin here)...what about right now!

GABA and stress 

Think of GABA as our nervous system's "brake pedal".

 

Learn about GABA here but it's key to understand that it's the primary inhibitory neurotransmitter engine in the brain and nervous system.

 

The key understanding with stress is that GABA directly opposes Cortisol, our primary stress mediator.

 

It even calms the initial trigger of stress, CRH (sometimes called CRF for "factor": 

GABA reduces the secretion of corticoliberin (corticotropin-releasing hormone, CRH), which triggers a series of consecutive hormonal changes, leading to secretion of cortisol by the adrenal cortex [44, 45]. 

https://link.springer.com/article/10.1007/s00217-016-2772-3

 

When things are stressful, you see these two battle out for brain supremacy (or state control) but in a more nuanced way, they also manage the sleep/wake cycle.

 

Cortisol isn't all bad...we need it to wake up and be alert at lower levels.

 

Too much GABA isn't good either as we can see from overdose effects from benzos and barbiturates (even alcohol - see CBD versus alcohol).

 

Benzos directly spike GABA (along with dopamine...hence the addiction risk) but they hit like a hammer which causes tolerance (longer-term reduction of natural GABA - see CBD versus benzos).

 

GABA has an almost immediate effect on stress.  If we can support this pathway without tolerance and addiction, that's a powerful tool (more on that below).

 

Think of serotonin as our ocean of stress response and GABA as individual waves.  Long-term and short-term effects (tonic versus phasic).

 

Finally, let's look at our backup stress response player.

Anandamide and stress 

This is one of the two heavy hitters in the endocannabinoid system.

 

The endocannabinoid system is a very old system (about 600 million years old) that we all share with every animal on Earth...highly conserved.

 

It's tasked with balancing other key systems when they come under stress: 

  • Nervous system - neurotransmitters like GABA, serotonin, and more
  • Immune system - inflammation and cellular birth/death cycle
  • Endocrine system - hormones such as cortisol, CRF, and more

 

Now, we have to clarify our use of the word "stress" here.

 

This is anything that pushes one pathway in the body up or down away from balance or homeostasis.

 

For example, if we hear rustling in a bush, there's a sudden startle response, and the cascade of stress (right up to fight or flight) kicks in.

 

Once we realize that it's just a rabbit and not a tiger, this whole escalation needs to calm back down.

 

That's the endocannabinoid system!  Back to balance.

 

The issue is with chronic stress or traumatic stress.  Too long or too much.

 

The endocannabinoid system can't keep up.

 

Anandamide is one big player here (2AG being the other).

 

Almost every cell in your body has CB1 and CB2 receptors where anandamide interacts.

 

Anandamide is named after the Hindu goddess of bliss, Anand so that gives you some indication of how it "feels".

 

THC, the cousin of CBD (See CBD versus THC) mimics anandamide and plugs into the same receptor.

 

Anandamide can be thought of as the chemical that keeps you just high enough (upbeat, satisfied, curious, etc).

 

When things get stressful, it has a direct response of calming our response down.

 

Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD. 

https://www.nature.com/articles/s41380-018-0215-1

 

Ahhh...FAAH, the best-kept secret in health.

 

See our review of the woman who can't feel anxiety, depression, or pain (no FAAH).

 

One note...anandamide is made on-demand and almost immediately removed by FAAH.

 

THC hits like a hammer and can't be removed as quickly, hence the "high" effects and other issues (tolerance being the big one).

 

You'll see anandamide spike in situations of severe stress such as with schizophrenia as the endocannabinoid system is desperately trying to right the ship (see CBD and schizophrenia).  In that case, the S.S. Dopamine.

 

We'll look at CBD's effect in this pathway below.

 

Okay...so those are the players both PRO and AGAINST stress.

 

What happens if there's a mismatch (too long or too much stress)?

 

Just about every health issue you can think of!

Key issues tied to stress overload 

A series of issues arise from elevated and protracted stress.

 

Again, stress here and there - episodic - is fine as long as it's not overwhelming (trauma) but chronic stress really is the enemy.

 

So much for our modern lifestyle!

 

To put a point to it: 

Stress is the common risk factor of 75%–90% diseases, including the diseases which cause the foremost morbidity and mortality. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476783/

 

Let's just hit some highlights: 

  • Heart
  • Mental health
  • Auto-immune
  • Metabolic disorders

 

We just ticked off probably 80% of our chronic health issues so it's a good start.

 

First, heart.

 

Heart and chronic stress

 

Cortisol is a chemical call to action.  Danger!

 

Needless to say, the heart responds with increased blood flow, heart rate, and blood pressure.

 

All the things needed to get things moving.

 

Chronic stress has been shown to increase the heart rate and blood pressure, making the heart work harder to produce the blood flow needed for bodily functions. Long-term elevations in blood pressure, also seen with essential hypertension (high blood pressure not related to stress), are harmful and can lead to myocardial infarction (heart attack), heart failure, abnormal heart rhythms, and stroke. 

https://jamanetwork.com/journals/jama/fullarticle/209139

 

It's like red-lining an engine every time you drive.

 

Long term exposure to cortisol, our primary stress player is also suspect: 

Studies suggest that the high levels of cortisol from long-term stress can increase blood cholesterol, triglycerides, blood sugar, and blood pressure. These are common risk factors for heart disease. This stress can also cause changes that promote the buildup of plaque deposits in the arteries. 

https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=1&ContentID=2171

 

We'll look at the effect of stress on immune function and inflammation which is key to this whole process.

 

Let's turn to the brain.

Mental health 

The two biggest factors for drug relapse?

 

 

Since stress directly eats up GABA and serotonin, it's very simple to see how chronic states (or very intense) would cause issues.

 

Every mental health issue has some tie-in with stress.

 

We'll look quickly at the big ones: 

  • Anxiety
  • Depression
  • Schizophrenia (as a developmental example)

 

First anxiety.

 

The transition from stress to anxiety is pretty straightforward (see pathways of anxiety).

 

Stress eats up GABA, our immediate calm agent, and also serotonin, our longer-term calm agent.

 

We're more curious about early stress and anxiety states later in life.

 

For example: 

Early life stress produces long-term alterations in cognition, emotionality, and stress responsiveness. 

https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.20862

 

We looked at how to unwind this "Trauma" here.

 

In fact, a major mood hub in the brain called the hippocampus gets "remodeled" from stress early on.

 

The amygdala (our fear center) also becomes hyperactive or "vigilant" as a result of stress.

 

See CBD and anxiety pathway 

 

What about depression and stress?

 

We did a deep dive into CBD and depression.

 

You can think of depression as a slow disengagement of the brain.

 

This can be due to the harmful effects of overactive immune systems, chemicals, and….chronic stress!

 

Literally, stress ramps things up and burn out the brain.

 

Serotonin is a big player here.

 

SSRIs, the most common medication for depression, work for the estimated 30% of people by boosting serotonin (till they don't due to tolerance - see CBD versus SSRIs).

 

Serotonin wears many hats and not only is it a stress response buffer, but it drives BDNF, our brain's fertilizer.

 

This is key to keeping the brain "engaged" in the face of so many assaults (inflammation, infection, injury, stress!).

 

See how SSRIs really work or CBD and brain repair.

 

What about auto-immune?

Auto-immune 

We did a deep dive on auto-immune here.

 

The root of this class of issues (from arteriosclerosis to psoriasis to dementia) is inflammation and hyperactive immune response.

 

Gut inflammation and gut barrier breakdown is really the Trojan horse.

 

First, a walk through the data.

 

Is stress tied to autoimmune? 

Comparing more than 106,000 people who had stress disorders with more than 1 million people without them, researchers found that stress was tied to a 36 percent greater risk of developing 41 autoimmune diseases, including rheumatoid arthritis, psoriasis, Crohn's disease and celiac disease 

https://www.webmd.com/balance/stress-management/news/20180619/severe-stress-may-send-immune-system-into-overdrive

 

The more severe, the higher the risk.

 

What's going on here?

 

It's about ramping up the immune system into overdrive!

 

Like we said...you have to go to the gut which acts as a thermostat for inflammation throughout the body: 

A recent study in mice reveals that persistent social stress changes gut microbiota, or microorganisms, in ways that can trigger certain immune responses. 

https://www.medicalnewstoday.com/articles/325193

 

We're not surprised.  See CBD and gut inflammation or CBD and probiotics for anxiety.

 

Speaking of the gut...

Metabolic disorders 

Diabetes and the entire suite of metabolic dysfunction (cholesterol, blood sugar, etc) is directly tied to chronic stress.

 

When your body is constantly in a low-level fight or flight (chronic stress) the body makes distinct changes to our metabolic process...

 

After all, if you're about to be eaten by a tiger, energy is needed now!

 

The effect of cortisol and stress hormones on diabetes is bad when long term: 

Specifically, cortisol is negatively associated with potential compensatory mechanisms for insulin resistance, such as increased β-cell function and increased insulin release to a glucose challenge, by exacerbating the progression toward insulin resistance in this population.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050109/

 

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It's across the board for metabolic agents: 

There was statistically significant increase in serum cortisol, adrenaline, Total cholesterol, HDL-cholesterol and LDL-cholesterol levels in students under examination stress compared to the non examination period 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370130/

 

So were just three big examples of health effects from prolonged or traumatic stress.

 

Let's zero in on inflammation...the axis through which this all interacts.

Stress and inflammation...especially in the brain 

All the exciting new research is around the immune system.

 

Turns out it's not just about fighting infection.

 

Stress is intimately tied to inflammation and heightened immune response.

 

Chronic stress leads to low-level chronic inflammation...and that's not good.

 

Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476783/

 

This chronic inflammation is tied to just about every problem you can think of.

 

Even aging itself!

 

During aging, chronic, sterile, low-grade inflammation — called inflammaging — develops, which contributes to the pathogenesis of age-related diseases. 

https://www.nature.com/articles/s41574-018-0059-4

 

We looked at Vitamin D here and Steroidal hormones here on whether decreasing levels of these are tied to this inflammaging.

 

Let's go one level down...to cytokines.

 

Cytokines are the actual foot soldiers of inflammation.

 

Stress, she says, causes the body to release pro-inflammatory cytokines, immune factors that initiate responses against infections. 

https://www.scientificamerican.com/article/stress-dangers/

 

This makes sense.  If there's danger, we may infection or injury to come.

 

The immune system ramps up.  If this happens chronically, you get… low-level chronic inflammation.

 

Let's take a quick detour to the brain.

 

Stress in the brain ramps up inflammatory generals called microglia: 

There is consistent evidence that a range of psychosocial stressors lead to elevated microglial activity in the hippocampus and good evidence that this is also the case in other brain regions.  

https://link.springer.com/content/pdf/10.1007/s00213-016-4218-9.pdf

 

Remember...the microglia not only respond to infection but they manage the architecture of the ever-changing brain: 

Interestingly, psychological stress can perturb the function of microglia in association with an impaired neuronal plasticity and the development of emotional behavior alterations. 

https://d1wqtxts1xzle7.cloudfront.net/43470667/Microglia_in_neuronal_plasticity_Influen20160307-19062-7029y0.pdf

 

"Impaired neuronal plasticity" basically means the inability to change and adapt within the brain.

 

It's at the heart of depression, anxiety, and every mental health issue you can think of.

 

Brain inflammation is bad for business.

 

Neurogenesis is the opposite...making new connections and even neurons. 

 

To learn why this is important, check out CBD and neuroinflammation or CBD and brain repair.

 

Let's finally move to ways to counter stress and its effects.

How CBD works for stress response 

Finally...if you've stuck with us this long.

 

Where does CBD fit into this whole equation?

 

Remember the endocannabinoid system with anandamide (the bliss molecule)?

 


It's tasked with balancing other key systems...all tied to stress response and suppression.

 

CBD is one cannabinoid or a chemical from outside the body that impacts this system.

 

What makes CBD so interesting for health is how it interacts with the above system.

 

CBD's primary driver is that it slows down FAAH (the chemical that eats up anandamide, our stress response backup system).

 

This manifests in almost every pathway of the body and brain.

 

For example.

 

CBD is a positive allosteric modulator of GABA, serotonin, and glycine in the brain and nervous system.

 

This is very important...let's explain.

 

Basically, it works like a feedback mechanism when these key neurotransmitters get exhausted.

 

We don't want to just boost these important chemicals in one direction or we run into the same issues with benzos/barbiturates (GABA) or SSRIs (serotonin).

 

Tolerance.

 

Basically, when a substance pushes a key pathway in one direction, the body starts to push back over time and you actually get less natural production.

 

This is why you have withdrawals (along with any pumping of dopamine...our reward pathway).

 

The actual DNA gets turned off to make the 5 proteins that make up the GABA receptor after prolonged benzo use.

 

It can take 30 days for those to get replenished (see how we weaned off benzos).

 

Same if not longer for serotonin receptors and SSRIs.  

 

CBD will support GABA (and its inhibitory compatriot, glycine) and serotonin when low but not when high.

 

We'll look at the studies below.

 

CBD also operates this way for the opioid system (physical and psychological pain), inflammatory pathways (tied to anandamide), and other smaller pathways.

 

Basically, anywhere anandamide functions (we have CB1/CB2 receptors on every cell of the body except red blood cells), CBD supports balance.

 

Learn how CBD actually works here or what exactly is CBD.

 

Okay...enough of the broad strokes… let's get down into the stress weeds.

CBD and CRF 

Let's start at the start.

 

To cut to the chase: 

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/

 

The fascinating piece is that CBD did not affect CRF in non-stress periods.

 

Further confirmation that it supports when needed!  We can't tell you how important this is due to the tolerance effect.

 

An example with inflammation and CBD below (for cancer) will put a point to it.

 

The study also showed how serotonin was critical in this effect on the stress cascade.

 

See CBD and CRF for more info.

 

The next step in the cascade...our major stress responder.

CBD and cortisol 

Speaking of mental health, a study looked at people at high risk of psychosis (see CBD and psychosis).

 

We'll walk through these studies: 

The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113209/

 

To translate this (please!!), there were three groups responding to stress: 

  • Control group 
  • High risk with no CBD
  • High risk with CBD 

 

Essentially, the addition of CBD brought the high-risk group closer in response to the control group!

 

It normalized their response.

 

Check our CBD and public speaking review which really dives down into this process.

 

Especially, the subjective (everyone's looking at me… I'm stressed) effect of CBD.  Very fascinating.

 

The key piece is this...CBD calms cortisol activity when too high it doesn't sedate and messes up the sleep/wake circadian cycle.

 

Remember that cortisol is important to make us alert/awake during the day.  We don't to be "sedated".

 

Check out Can you take CBD in the middle of the day to see this research.

 

However, at night time when cortisol can be the enemy to sleep (exhausted GABA), there's a clear rebalancing from CBD.

 

Check out CBD and sleep here.

 

Let's turn to our stress response systems.

CBD and serotonin 

This may be for favorite for stress response...especially long-term healthy stress response.

 

Serotonin is the master regulator of ALL human behavior.  Period.

 

Check out our serotonin review.

 

It's the big defense against too much stress.  Hence all the hype around tryptophan, 5HTP, and SAMe.

 

Tryptophan is great but the other two can have weird effects depending on histamine response.

 

Again...we don't want to just pump serotonin in one direction as too much serotonin is just as bad as too little  (see serotonin syndrome).

 

CBD supports serotonin when low and here's a wonderful example: 

Overall, 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/

 

Let's break that down because it's pretty impressive.

 

They basically cause a depletion in serotonin function due to an injury.

 

Serotonin also manages our pain threshold (go figure).

 

CBD was able to reduce pain (support threshold) and reduce anxiety (the psychological effect of physical pain). 

 

How did it do this?

 

"Rescue" of serotonin (5-HT) function.

 

Goodness.  We can drop the mic right there.

 

Here's the bigger picture piece.

 

Serotonin is key for shaping how we respond to stress now AND in the future.

 

It drives BDNF (brain fertilizer) which rebuilds, replenishes, and grows our brain's connectivity.

 

Simply put:

Activation of postsynaptic 5-HT1A receptors improve stress adaptation 

https://pubmed.ncbi.nlm.nih.gov/24258351/

 

Stress isn't going away...our adaptation to how we deal with it is key!

 

Serotonin takes time to work since the heavy lifting is actually BDNF (about 2 weeks).

 

What about right now?

CBD and GABA 

GABA is the immediate stress responder since it pushes back on cortisol.

 

Check out GABA and anxiety here.

 

CBD is technically a positive allosteric modulator of GABA.

 

This means that it supports it when out of balance (on the low side).

 

Studies on anxiety have also pointed to this pathway since GABA exhaustion also figures in strongly there: 

The anxiolytic effects of systemic CBD partially depended on GABAA receptor activation in the EPM model  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

 

Anxiolytic just means anxiety-reducing.

 

You can see CBD's direct effect on pathways here: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/

 

You'll see CBD's effects on both GABA and glycine.

 

This also figures into sleep.  Just a head's up...the main anxiety and sleep meds work like sledgehammers on GABA pathways but they cause tolerance (and addition from dopamine spiking) as a result.  See CBD versus benzos or CBD versus Ambien.

 

CBD doesn't build tolerance, doesn't cause addiction (actually normalizes dopamine), and it not hedonic (pleasurable).

 

Keep in mind that GABA is integral to pain (especially neuropathic), stress response, sleep, mood, and brain integrity.

 

Let's turn our attention to the endocannabinoid system.

CBD and anandamide 

We mentioned anandamide up above….the heavy hitter in our balancing system.

 

If GABA is overwhelmed and serotonin gets exhausted, anandamide is called in to assist.

 

Anandamide has powerful stress buffer effects as we can see from its corresponding receptor: 

CB1R activation is essential to negative feedback of the neuroendocrine stress response and protects against the adverse effects of chronic stress 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/

 

Goodness...push back on immediate stress and protection from chronic stress.

 

This may be the linchpin for poor stress response in our hurried world!

 

Let's set up CBD's effect here.

 

Remember that FAAH eats up anandamide.  People with less FAAH have less anxiety, depression, pain, inflammation, etc.  This can be a genetic trick.

 

What does CBD do here?

 

CBD increases anandamide levels by inhibiting its transporter-mediated reuptake and degradation by FAAH 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486906/

 

That in itself is interesting but look at the net result of this (and BDNF neurogenesis): 

Evidence from preclinical studies has shown that the non-psychotropic phytocannabinoid cannabidiol and the endocannabinoid anandamide have acute anxiolytic effects and also regulate learned fear by dampening its expression, enhancing its extinction, and disrupting its reconsolidation.

 

Anxiolytic just means anti-anxiety.

 

Been there...done that.

 

But keep reading...CBD via anandamide aids the reduction in response to current and PAST fear.  Fear extinction...forgetting stressful or traumatic events.

 

Even blocking it from being locked into our memory including the emotional coloring of it.

 

Again, see our CBD and trauma to learn more.

 

So, that runs the gamut from immediate stress response to chronic stress to unwinding traumatic stress effects.

 

Anandamide's a pretty special guest!

 

Let's go to the absolute extreme in stress levels...to the point of psychosis.

 

This is most telling for CBD and stress response:


Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

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

 

See CBD and schizophrenia (where anandamide is woefully trying to right the ship) for more info.

 

Finally...you can't talk about stress without bringing up brain inflammation.

CBD and brain inflammation (immune response) 

Remember how stress hyperactivates the immune system in the brain including the microglia?

 

Microglia release glutamate (opposing force to calming GABA) when in this state.

 

Excess glutamate is highly toxic to the brain and has implications from depression (brain retrenching) to anxiety to just about every mental health issue you can think of.

 

First, cortisol release causes a spike in oxidative stress: 

The prolonged exposure to elevated cortisol levels has been shown to cause an increase in reactive oxygen species (ROS) at the cellular levels and increased oxidative stress 

https://www.tandfonline.com/doi/abs/10.1080/10538712.2016.1123790

 

ROS are little chemical scissors that cut through anything around them. We have a whole system to keep these under wraps since they're destructive to our brain's valuable real estate.

 

CBD is a powerhouse here even compared to the common anti-oxidants we all know and love: 

CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C [4]. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/

 

Check out CBD and oxidative stress or CBD and glutathione.

 

Many studies have looked at CBD's ability to reduce general brain inflammation and this is no more apparent than studies following stroke (ischemia): 

Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia 

https://pubmed.ncbi.nlm.nih.gov/27889412/

 

Not only did it calm the inflammatory storm but it bolstered BDNF, the repair crew after injury.

 

See CBD and brain repair or CBD and TBI.

 

What about those hyperactive microglia?

 

cannabidiol (CBD) has emerged as a promising strategy to treat inflammation that results from microglial hyperactivation [78], with no psychotropic side effects. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386505/

 

Check out our review on CBD and neuroinflammation!

 

One final aside on hormones and stress.

Steroidal hormones and stress response 

We won't belabor this too much but you have to evaluate levels of steroidal hormones when talking about the stress response.

 

  • Estrogen directly drives serotonin
  • Progesterone directly drives GABA

 

They both modulate immune response (yin-yang) and nervous system function.

 

Testosterone is a whole different deal that's integral to stress response...even in women!: 

the androgen steroid testosterone, the end product of the hypothalamic–pituitary–gonadal (HPG) axis, down regulates the integrated stress response at multiple levels. 

https://tahomaclinic.com/Private/Articles4/Stress/Hermans

 

The net effect of testosterone on stress?  "It's all going to be fine".  

 

Seriously, to a fault as many women can contest with their significant others.

 

Progesterone and testosterone drop significantly from around age 20 while estrogen goes on a roller coaster ride in your late 40's before plummeting.

 

Learn more at our progesterone, estrogen, and testosterone reviews.

 

Especially...if you're in your 40's or later.

 

Let's get to practical questions.

How much CBD to take for stress 

This depends on the severity of the stress and resulting symptoms.

 

Baseline levels of CBD for immediate stress response are likely between 30-50 mg daily.

 

Studies looked at very serious stressors (such as public speaking) at 600 mgs about 1 hour before the event.

 

Check out CBD and performance anxiety to learn more.

 

Withdrawal from opioids (just a tad stressful) pointed to 600-800mg the first 10 days and then 300mg after.

 

See CBD and opioid withdrawal or CBD and addiction (which has a huge stress component for relapse).

 

Peak neurogenesis, the repair process, is around 300mg daily.

 

  • For general stress response, the levels are likely between 50mg and 300mg...again depending on severity.
  • For extreme stress, research points to up to 600 mg.

 

You can hold the CBD oil under your tongue for up to 60 seconds to boost availability and even break up doses within a day.

 

What about the type of CBD?

What's the best CBD for stress response support 

There are basic requirements with CBD: 

  • From organically grown US Hemp at an FDA registered farm
  • CO2 processed
  • 3rd party tested
  • No THC (builds tolerance on the anandamide pathway)
  • No Heavy Metals
  • No Pesticides
  • No Bacteria
  • No Mold

 

We make sure all these requirements are met for IndigoNaturals with 3rd party testing at the top of every page.

 

Then there's full spectrum versus CBD isolate.

 

All the research (100's of studies) are on CBD isolate.  CBD by itself.

 

More importantly, 40-60% of the population has histamine issues and that number goes up as we get older and for women (thanks for leaving progesterone!).

 

Histamine (player behind allergic reactions) is incredibly important in our stress response.

 

In the brain, it's excitatory just like glutamate.

 

In fact, histamine opposes GABA in a similar fashion to cortisol.

 

To make matters worse...acute stress causes a rush of histamine response (be more alert for the impending danger): 

These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL-1 and secondly of CRF. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2343625/

 

We see many people who have pretty strong side effects to full-spectrum CBD only to see those go away with CBD isolate.

 

It's likely the histamine response!

 

Check out CBD isolate versus full spectrum to learn more.

 

Finally, there's cost.

 

The key metric there is the cost per mg of CBD.

 

We specifically price our CBD between 2-6 cents before discounts up to 50%.

 

Our discovery of CBD was due to a brutal perimenopause experience so if we can help people find relief, it's well worth it.

 

Reach out to us (chat to the right...we always respond with lots of detail).

 

Be well. Take care of each other.  Take care of yourself!

 

shop cbd isolate oil online 

 

Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

 

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