How Exactly Does CBD Work in The Body and Brain
February 07, 2021
We're finally in a good place to write this.
1 million-plus words on CBD research with deep dives across multiple pathways sheds quite a bit of light on exactly how it works.
There's quite a bit of hype surrounding CBD these days.
A modern cure-all. That's how it's positioned by marketers.
The truth is quite a bit more subtle but very intriguing.
Once you understand how CBD works within a key system of our body, the endocannabinoid system, it all starts to make sense.
The biggest trick up CBD's sleeve is what it doesn't do...build tolerance. We'll explain below why this is so important.
Let's get into it!
These are the topics we'll cover:
- A quick intro to the endocannabinoid system
- How does CBD work in the endocannabinoid system?
- What pathways does CBD affect in the body and brain CBD boosts BDNF
- CBD blocks FAAH and boosts anandamide in a natural way
- CBD balances and supports serotonin
- CBD boosts BDNF
- CBD balances GABA and glutamate
- CBD calms immune response under chronic conditions
- CBD supports gut health and gut barrier
- CBD calms excess glutamate for nerve damage and repair
- CBD calms oxidative stress
- CBD calms Calm systemic inflammation
- CBD supports mitochondria health
- The real difference between CBD and THC
- How much CBD is needed to work
- What's the best CBD to have positive effects
Let's get started...lots to cover.
A quick intro to the endocannabinoid system
First of all...what exactly is an endocannabinoid system?
You have one working in you right now (hopefully!).
It dates back about 600 million years and we share it with all animals.
Your cats and dogs also have one!
Simply put, it's the system of balance.
Bringing other key systems back to normal after they run hot or cold.
Scientists use the term "stress" but not in the way you think of it.
Any external push on a system up or down is countered by the endocannabinoid system.
For example, if you (or our ancient ancestor) hear stirring in a bush, we immediately have a flight or fight response.
- Heart rate quickens
- Blood pressure goes up
- Pupils dilate
- Cortisol (our stress hormone) shoots through the body
We know the drill.
When you realize it's a squirrel and not a tiger, all this needs to come back to baseline...it's not intended to stay that way (which is the issue with chronic stress).
The endocannabinoid system is in charge of this "rebalancing process".
Technically, it's called homeostasis and there are 100's of pathways that operate on push-pull mechanisms that need constant balancing.
The three big systems that we focus on under direct supervision of our endocannabinoid system is:
- The nervous system - neurotransmitters and more
- The endocrine system - hormones including those dealing with metabolism, energy, and stress response
- The Immune system - immune response, inflammation, and cell birth/death cycles
Pretty important and directly tied into almost every modern disease you can think of.
- Autoimmune? Check
- Mental health? Check
- Cancer? Check
There's a whole suite of chemicals naturally occurring in your body right now which carry out the orders of this system.
Anandamide and 2AG are big players with a slew of supporting role agents.
Anandamide is called the "bliss" molecule and literally named after Anand the Hindu goddess of bliss.
It's a powerful anti-stress agent. Its goal is to keep us a little bit "high" - you know, that feeling when you're positive, upbeat, and resilient!
We'll get into how THC carries this whole process a bit too far below.
2AG is more nuanced and acts as a workhorse for this balancing act system.
We have two main receptors that they interact with:
- CB1 found primarily in the nervous system
- CB2 found throughout the body with strong effects on the immune system
Let's zero in a bit to add some detail.
GABA and glutamate (the "brake" and "gas" pedal in our brains) are a perfect example.
There are system-wide and even minute neuron-by-neuron ebbs and flow between these two that are key to your brain functioning correctly.
We covered this in detail at our CBD and GABA or CBD and glutamate.
Sleep. Anxiety. Even depression all rely on a balance between these two.
In fact, benzos directly target GABA. So do sleep medications. Till they don't due to tolerance.
That's a great segue into CBD.
How does it work in the endocannabinoid system?
This is why we wrote a million+ words to begin with!
How does CBD work in the endocannabinoid system?
CBD is a member of the cannabinoid system. Basically, chemicals found in the cannabis plant are able to fit into the receptors of our endocannabinoid system.
THC and CBD are the dominant cannabinoids with some lesser-known side-players (CBC, CBG, CBN, etc).
By volume, it's a THC and CBD show, however.
THC mimics anandamide in structure so it's able to fit right into our CB1 receptors.
This is the basis for the "high" feeling as it directly promotes activity in a very strong manner (compared to anandamide).
CBD is much more nuanced and that's really its power in terms of use.
Technically, it's called an allosteric modulator.
Goodness, what does that mean?
Essentially, it's a feedback mechanism!
Where THC says "more more more CB1 activity", CBD send a message backwards and says:
- "we're fine over here, stop sending"
- "We're running low, send more"
We see this feedback response across every pathway we've investigated.
Inflammation and cancer is a perfect example:
- Healthy cell or neuron with low inflammation - CBD has no effect
- Healthy cell or neuron with high inflammation - CBD reduces inflammation
- Cancerous or virally-infected cell - CBD INCREASES inflammation!
Read that back over - three different responses depending on the state of the system.
The third one makes sense once you realize that our immune system's natural way to get rid of awry cells is to jack inflammation and kill them.
It does this in the form of oxidative stress (see CBD and oxidative stress).
Chemo and radiation are essentially massive doses of oxidative stress. We have a massive review on CBD and Turkey Tail for cancer pathways.
This feedback mechanism is why we don't see overdoses at pretty high levels in research (1500 mg doses).
In fact, the side effect profile doesn't change much as we go up the scale which is fascinating.
On the flip side, there are powerful effects on the pathways directly tied to mental health, inflammation, and more.
This speaks to the pathways directly affected by CBD.
Our favorite chart is here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/
CBD affects the widest swath of pathways including some real powerhouses:
- GABA - target of benzos and key to mental health, pain, and sleep (see CBD versus benzos)
- Serotonin - master regulator of all human behavior and target of SSRIs (see CBD versus SSRIs)
- Opioid system - key to pain, both physical and psychological
- Anandamide reupdate - very different than directly boosting like THC
The other cannabinoids might hit 1-2 pathways...which are already covered by CBD!
Here's the key….the other cannabinoids, especially THC, operate as agonists.
This means that they boost levels in one direction!
CBD doesn't...it operates in its feedback way (allosteric modulator).
This is the most important aspect to understand across our entire website and here's why...
When you boost a pathway in one direction, the body panics and actually counters the effect long-term.
Let's take GABA as an example.
Benzos will jack up GABA levels...one direction.
Feels great for anxiety and sleep at first but then the body starts to panic from this outside influence way beyond its natural bounds.
It will literally reduce the sensitivity and number of GABA receptors down to the genetic level (stops making the 5 proteins needed for the GABA receptor).
That's why a person who's been on benzos long term can have brutal withdrawal symptoms and even seizures (no more "brake" pedal naturally).
The body goes so far as to boost glutamate (the "gas" pedal in our nervous system).
We've actually made the whole situation much worse! The opposite of what we were trying to do.
Of course, benzos also jack up dopamine, which is key to addiction (see CBD and addiction or CBD and dopamine).
What about CBD?
Research shows that:
- CBD does not cause tolerance
- CBD is not addictive
- CBD can help to normalize and balance these systems
In fact, there's quite a bit of fascinating research on CBD and addiction as re-wiring the "learned" process of addiction in the brain is critical as is normalizing the systems such as GABA above.
Again, this process of tolerance occurs with more long-term use but there's a black box warning on benzos beyond 2 weeks so it's not that slow!
Almost every drug in our arsenal works in one direction.
That's why you have side effects...the key to our very complicated health is a balance which as we now know, is the direct result of a healthy endocannabinoid system.
We did deep dives into endocannabinoid deficiency.
Let's highlight some of these pathways since you may not be researching this stuff hours a day like we do (a compliment, not an insult).
What pathways does CBD affect in the body and brain?
We're going to hit some of the highlights that are really powerful for health and wellness.
Our top 10 pathways would be as following:
- Blocking FAAH and boosting anandamide in a natural way
- Balancing and supporting serotonin
- Boosting BDNF
- Balancing GABA and glutamate
- Calming immune response under chronic conditions
- Supporting gut health and gut barrier
- Calming excess glutamate for nerve damage and repair
- Calming oxidative stress
- Calming systemic inflammation
- Supporting mitochondria health
We had to cherry-pick our favorites since there are hundreds of discrete systems affected.
To some extent, many of these are knock-on effects from the above 10.
Let's explain why they're so important.
CBD blocks FAAH and boosts anandamide in a natural way
FAAH will be one of the first targets for CRISPR gene editing.
You could literally dial down pain, anxiety, inflammation, depression, and more.
Read about the lady who can't feel pain or anxiety due to a rare FAAH gene variant.
CBD eats up FAAH which allows anandamide to hang around longer.
This has really powerful effects when we're under "duress". I put that in quotes because duress can come in many forms depending on the system in play:
- Trauma
- Infection
- Chronic stress
- Pain
- Social rejection
Again, think of something bad and it's probably taxing anandamide.
For an extreme example from research on CBD and schizophrenia:
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316151/
We have a monster review on CBD and schizophrenia and psychosis.
Interestingly, too much THC can actually induce psychosis (temporarily) which shows you how powerful the feedback mechanism of CBD is compared to one-direction pushing of anandamide's pathway.
It's not just that though...anandamide is a key calming agent across the body and brain. This is probably the furthest reaching effect of CBD.
Read the article on endocannabinoid deficiency to learn just powerful it can be.
Let's to turn one of our favorite targets.
CBD balances and supports serotonin
We did a deep dive on CBD serotonin for an important reason.
Serotonin governs all human behavior!
That's not hyperbole.
It's called the "feel good" neurotransmitter but that doesn't do it service.
Too much or too little serotonin feels really bad!
"I feel like I'm dying" bad.
SSRI's, the most common antidepressants, boost serotonin...but in one direction!
That should start up some warning bells. We did a look at CBD versus SSRIs here.
Besides, genetic differences, the various assaults we listed above can draw down serotonin:
- Trauma
- Pain (physical and psychological)
- Infection
- Stress
Here's a perfect example where injury was used to eat up serotonin function with CBD's effect:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
So…
- CBD restored the pain threshold
- Reduced anxiety
- Balanced serotonin (5HT)
Goodness. See how pain can really send ripples across the body and brain.
Psychological pain has the same effect . The body's systems (such as serotonin) can't really tell the difference.
We have big reviews on CBD and depression and how SSRIs really work to showcase how CBD interacts with this system.
It turns out that serotonin has a very powerful downstream effect which is key to all of this.
That's our next section.
CBD boosts BDNF
The new hot topic in mental health is neurogenesis.
It's a technical word for brain repair/replenishing.
Our nervous system is in a constant battle between cellular death and birth.
The death side may sound familiar:
- Injury
- Stress
- Excess glutamate
- Trauma
- Inflammation
- Infection
- Oxidative stress
It's a constant tug of war between the forces of good and evil...in our brain!
We did a huge review of how early trauma, infection, or stress can upset the entire apple cart (and how to reverse it).
The wear and tear of just supporting our most energy-hungry part of the body (the brain...close runner up is the heart) changes with every sentence you read.
What keeps the forces of darkness at bay?
BDNF and the neurotrophins. It may sound like a poorly-named rock band but it's key to healthy brains and nervous systems.
BDNF is the brain's fertilizer. Point.
It's why SSRIs take about 2 weeks to start working (before tolerance kicks in) ...building a brain is not an overnight thing.
It's key to mental health (all mental health).
- Depression is brain atrophy (loss of connectivity and brain mass in the pre-frontal cortex)
- Anxiety is brain loss in the hippocampus and hard-wired anxiety circuit
- Addiction is literally a learned behavior wired into the brain
In fact, the most addictive drugs (meth, cocaine, opioids, etc) have been shown to turn down neurogenesis!
That's why people feel like they're stuck. They are...in the brain itself!
The two most common traits for lapsing recovery?
- Stress hormone levels
- BDNF levels
Why is exercise and mindful meditation so powerful for mental health?
BDNF
Why is psilocybin from magic mushrooms going to be the mental health blockbuster over the next decade?
BDNF.
Neuropathy? Pain syndromes?
BDNF.
Okay...okay...we'll stop. Just don't stop BDNF.
As for CBD's effect there?
Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex
https://pubmed.ncbi.nlm.nih.gov/29869197/
Synaptogenesis just means building new brain connections...literally the opposite of depression.
Check out CBD and neurgogenesis or CBD and BDNF!
This whole pathway gives us good guidance on the dosage of CBD which we'll look at later.
Next up, the delicate balance of GABA and glutamate.
CBD balances GABA and glutamate
This pathway is key to almost all mental health.
There's a delicate and complex balance between our primary excitatory (glutamate) and inhibitory (GABA) transmitters.
This balance can flux in different parts of the brain and drive the basic machinery of our brains.
We did deep dives on CBD and GABA as well as CBD and glutamate.
The big one is anxiety. Followed by sleep.
GABA is the target for benzos, the leading anxiety med, and sleep aids.
The issue is that they push GABA in one direction...up up up.
The body pushes back which is the basis for tolerance.
You end up worse than when you started over longer periods of time.
In the pathway chart above, we can see that CBD works in its feedback way for the GABA pathway.
Supporting GABA has a direct effect on anxiety, panic attacks, PTSD, OCD, and more.
Let's look at a study that ties it all together.
Researchers exposed mice to bacterial infection while in utero. There's a known risk between early infection and developmental mental health issues such as autism or schizophrenia.
We go deep into this at our CBD and autism or CBD and schizophrenia studies but here's the basic mechanism.
Remember above how we said that certain insults (trauma, infection, immune hyperactivation, etc) is overwhelming BDNF?
Excess glutamate is highly destructive in the brain. In fact, we have multiple systems working to keep it dialed in.
There's a great deal of buzz around NAC which acts as a sink for excess glutamate.
When the immune system is "primed" to run hot by early exposure to virus/bacteria, our main immune system responders called microglia to respond with inflammatory agents and….GLUTAMATE!
In the study with mice, look at CBD's effect:
Overall, these findings show that CBD can restore cannabinoid/GABAergic signaling deficits in regions of the brain implicated in schizophrenia pathophysiology following maternal poly I:C exposure.
https://pubmed.ncbi.nlm.nih.gov/31202911/
This may all seem like Klingon but it's so cool!
Learn more about our CBD and neuroinflammation for anxiety.
We even took a deep look at whether people who chronically smoke cannabis (THC) are really trying to calm glutamate.
After all, anandamide is a wet blanket on glutamate activity and we know from above how CBD supports anandamide.
Again, you can't underestimate this pathway as it's tied to everything in our brain.
Anytime the brain or an area is running too "hot":
- Anxiety
- Insomnia
- OCD
- Depression (damage to the prefrontal cortex)
- Panic attacks
- Phobias
- Seizures
- Pain (glutamate literally burns out the nerves)
Interestingly, a star of the show that doesn't get enough respect (yet) called glycine is also directly affected by CBD.
It works as a supporting role for GABA in the brain.
Really impressive results for sleep!
Let's move on or we'll never get through this!
CBD calms immune response under chronic conditions
In the last example, our immune system was hyperactivated by early exposure in utero to bacterial infection of the mother.
Research is finally understanding just how important the immune system is for total health.
Turn on a TV and you'll see a pharma ad and there's a good chance it's for autoimmune.
Those drugs primarily squash immune response or certain aspects of it.
The side effect profile of this process is not great if you listen to a fast-speaking voice listing a slew of nasty potential effects.
Again...pushing a critical pathway in one direction….down down down.
The goal there is to calm specific or systemic inflammation.
The problem is that inflammation is needed in the body periodically (infection and cancer).
We don't want to turn it off or you'll see very negative effects everywhere.
In fact, just yesterday researchers reported they were able to make mice walk again after spinal cord severing via a gene-edited cytokine.
Cytokines do the heavy lifting of the immune response...some inflammatory while others rebuild (like the one above with the mice).
Chronic inflammation however is brutal.
In our next section, we'll look at the common root for this (and the key to autoimmune) but for now, let's focus on rogue inflammation.
This may be CBD's biggest trick...a varied calming of inflammation when needed.
We see this across every pathway and in every issue we look at.
Check out our CBD and autoimmune review to really look at it but inflammation is key to many issues.
Mental health is wrapped around inflammation...inflammation in the brain.
Dementia is at its heart, an immune response issue (see CBD and dementia).
One example of CBD's effects tied to asthma (too much inflammation):
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/
What's the deal with IL10? Oh...it's one of the cytokines tied to calming inflammation!
Goodness. Again, this is one example.
The immune response is tied to:
- Allergies
- Mental health
- Pain
- Autoimmune
- Degenerative diseases
Interestingly (and quite differently from immune suppressant medications), CBD can actually bolster the immune system when needed.
For example with sepsis (systemic, deadly infection) and viral infection.
We did a huge review on CBD and cytokine storm and viral response but they're currently down due to increased scrutiny around anything virus-related.
As for mental health, the CBD and neuroinflammation is very interesting.
Let's turn to how bacteria/viruses make their way into our bodies, to begin with.
This is very critical for autoimmune.
South to the gut!
CBD supports gut health and gut barrier
This is critical and under complete attack these days.
Our gut barrier is a thermostat for system-wide inflammation.
More importantly, when the barrier between the outside world and our inner world breaks down, it's the linchpin for autoimmune.
We go into detail about this at our CBD and gut inflammation, CBD and leaky gut, and CBD and autoimmune.
Fascinating research is showing how bacteria (and viruses) can cross over and set off a chronic immune response.
The issue is that all living stuff is cut from the same basic building blocks and proteins in our cells which can resemble proteins made by bacteria.
Check out the connection between strep throat and psoriasis as an example.
This gut inflammation and resulting barrier breakdown is key to:
- Autoimmune including dementia, diabetes type 2, arthritis, and more
- Gut inflammation including IBS, Chrone's disease, and more
- Mental health issues with inflammatory markers - just about all of them
CBD is a powerful anti-inflammatory as we saw above but let's look at the gut barrier.
In a study on C diff (a very nasty bacteria) and its disastrous effect on gut inflammation and barrier, look at CBD's effect:
Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistance values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721977/
Goodness. Caco-2 cells are the important barrier cells for our gut.
Essentially, CBD helped to restore the gut balance after a very destructive bacteria interaction.
Again, read more about it in the reviews above.
Let's turn to glutamate.
CBD calms excess glutamate for nerve damage and repair
To some extent, this is the flipside of the GABA equation since the two are diametrically opposed.
Too much glutamate is highly destructive.
It's like redlining your engine...straight gas pedal...no brake.
This literally can kill neurons in the brain and lead to depression, anxiety, OCD, and just about every mental health issue.
A hyperactive immune response can also leak glutamate into the system.
As we travel out into the body, too much glutamate can destroy nerves by sheer exhaustion.
This is the basis for neuropathy, chronic and regional pain, and more.
In fact, the topical ketamine works for pain by giving peripheral nerves that feel pain a break from glutamate.
Nothing to do with the opioid system.
We know that CBD supports GABA directly to oppose excess glutamate but it goes further than that.
Let's introduce glutathione.
It's our primary anti-oxidant in the body but it also serves a critical function with glutamate.
Essentially, it acts as a sink for excess glutamate.
This is why the research on NAC is so interesting (see full review here).
What does CBD do for glutathione?
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/
Both of those chemicals help to break down oxidants.
And another pathway:
In addition, by preventing the formation of oxidative stress in the retina neurons of diabetic animals, CBD counteracted tyrosine nitration, which can lead to glutamate accumulation and neuronal cell death
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
Essentially, it's a supporter of nervous system function far and wide.
Glycine, the other pathway that CBD supports, it tied more to the spinal cord.
Let's zero in further to the oxidative stress pathway.
CBD calms oxidative stress
We mentioned above that CBD promotes glutathione, our body's primary way to neutralize the destructive effects of free-roaming oxygen.
Oxidative stress is incredibly destructive in our cells.
Right down to mutations in our DNA!
Check out our full review of CBD and longevity to see how this accumulates in the process of aging (along with what we think will be the biggest news over the next decade - David Sinclair's discovery that might reverse aging completely).
That was the hype behind Vitamin C and E...pretty powerful antioxidants.
How does CBD compare?
CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
Goodness...and they're major players.
Also check out fisetin and NAC.
We have a whole review on why oxidative stress is so important (especially in the brain) at our CBD and oxidative stress review.
Let's turn to general system-wide effects.
CBD calms systemic inflammation
Most of our modern diseases either result or accompany a general state of inflammation in the body.
You name it:
- Diabetes (all autoimmune for that matter)
- Pain - a major subsection of pain is directly tied to inflammation such as arthritis
- Mental health - check out the review of CBD and neuroinflammation to understand why - the "inflamed" brain theory
- Histamine and allergic responses - a subtype of inflammation - see CBD and mast cells or CBD and histamines
In fact, there are general "settings" for inflammation response in the body.
Keep in mind that inflammation is just a tool of our immune response to defend, destroy, and repair.
The two common settings are:
- TH1 - more reactive and inflammatory - generally for dealing with an attack
- TH2 - more calming and anti-inflammatory - for repair and coming back to normal after the threat is gone
The issue is when our body is constantly in a TH1 setting...hello modern diseases!
We go into why this happens at our CBD and endocannabinoid deficiency or CBD and gut inflammation (where the process really starts).
The endocannabinoid deficiency review is interesting because that system (which CBD works in) is tasked with balancing our response.
Clearly, it's overwhelmed!
So CBD's effect on this system-wide setting?
A study looked at CBD's effect in pre-diabetic mice:
Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.
https://www.tandfonline.com/doi/abs/10.1080/08916930500356674
That's a mouthful but let's translate!
Essentially, CBD dialed back key inflammatory agents tied to TH1 settings while increasing the repair/restore agents tied to TH2.
The net effect of this (which is the more important piece):
We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice.
NOD is short for non-obese diabetic.
Goodness...this should be front-page news considering the scale and ravages of diabetes.
Look at this crazy chart for diabetes:
The CBD completely countered the inflammatory response in asthma so that it was the same as people without asthma.
Check out CBD and diabetes or CBD and allergies.
CBD has big effects on inflammation via multiple pathways:
- CB1 activity - the anandamide connection - also check out PEA, a support player
- PPAR - a powerful pathway tied to inflammation response
- TRPV - another downstream pathway
In every main review, we look at inflammatory aspects since they're always front and center.
Let's finish up with mitochondria.
CBD supports mitochondria health
Mito-what??
You'll want to remember this one because it's key to energy, aging, and just about everything you do.
Mitochondria are the little power-plants of every cell in your body.
They also create a large amount of waste in the form of oxidation (see above).
Little versions of oxygen that slice and dice anything they come in contact with.
We want to do two things:
- Support proper mitochondrial function
- Mop up the destructive by-product (oxidation)
We covered the latter but what about the mitochondria function (which decreases as we get older)?
In difficult times, CBD is very much supportive:
Thus, under pathological conditions involving mitochondrial dysfunction and Ca2+ dysregulation, CBD may prove beneficial in preventing apoptotic signaling via a restoration of Ca2+ homeostasis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666323/
This is very important for situations like mitochondrial disease (see here).
Calcium is the basic currency of mitochondria and its balance is key to proper function.
Another study looked at brain neurons under stress (deprived oxygen such as with a stroke) and the effects of CBD on mitochondria:
Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons
https://www.sciencedirect.com/science/article/pii/S221323171630338X
Essentially, CBD reduced damage by bolstering mitochondria function when under duress.
Again, check out CBD and mitochondria or CBD and mitochondrial disease.
Keep in mind that mitochondria may be the linchpin for aging in general! See our longevity review.
Okay...that wraps up our specific ways that CBD works.
Let's touch base on the THC question. Are they the same thing?
The real difference between CBD and THC
So….they're cousins in the cannabis plant. Does CBD and THC work the same way?
THC directly boosts CB1 (the target for anandamide) activity.
In this respect, up to a certain dose, it will share many of the attributes that CBD does.
It will:
- Bolster stress response
- Suppress immune response
- Be neuroprotective
The issue is that it's an agonist...pushes in one direction...up up up.
CBD is a feedback mechanism.
That's why we don't see the "excess" side effects with CBD that we see with THC:
- Anxiety and psychosis
- Increased appetite
- Sedative effect
- High effect
THC is like a wet blanket on activity...primarily on the brain.
Here's the secret as to why.
Anandamide is readily made and removed on the fly. In and out of existence as needed.
That enzyme, FAAH, we discussed above does the removal bit.
The body is unable to remove THC in the same way so it lingers at levels much higher and longer than our body is built for.
One time may not affect much but chronically used and you'll get tolerance.
Literally, the body starts to reduce the number of CB1 receptors and sensitivity.
Long term, this is going in the wrong direction.
Interestingly, CBD can counter many of the "excesses" of THC including the side effects.
Check out why CBD is a must if you use cannabis.
In fact, the godfather of CBD research coined the phrase "entourage effect" to reflect this very relationship.
Two issues:
- Most brands use the entourage effect to push full-spectrum with very little research
- Most cannabis products even in the legal markets such as California have very high THC and little if any CBD
It's like a liquor store selling mainly Everclear.
See why selling high THC will eventually lead to lawsuits like you see with RoundUp.
One more big difference.
THC can pump up dopamine, our reward circuit neurotransmitter.
This is the heart of addiction.
THC appears to only show addictive risks for about 5% of the population but if you use any substance chronically, addiction is just a result of the tolerance we described above.
You can become an alcoholic by drinking every day! See CBD and alcohol addiction.
As we mentioned, our theory is that people who chronically use THC are trying to calm down glutamate in the brain.
There are other ways to do that! (such as CBD, NAC, PEA, etc).
CBD and THC operate quite differently in the body since one pushes the pedal non-stop while the other pushes when needed (and even pulls on the other side!).
Let's turn to dosages since so much product out on the market is pretty much useless based on research.
How much CBD is needed to work
First, everyone's chemistry is different (weight, liver processing, etc).
- 40-50 mg daily is generally a good wellness dose
- Research on sleep shows effects at about 160mg daily
- Neurogenesis (brain repair) peaks at 300 mg daily
- Research on more serious or acute (need help right NOW) is at 600-800mg
The latter comes from research spanning the gamut for opioid withdrawals to schizophrenia and even public speaking.
Our favorite benchmark is 300 mg for the neurogenesis.
This is key to mental health and addiction.
It also speaks to when key pathways turn on and off (CB1 and PPAR versus TRPV).
In our review on CBD and stopping benzos, we looked at:
- 10 days (the withdrawal period) at higher amounts 600-800mg daily
- 2 months (the recovery period) at the 300mg for neurogenesis
Check out CBD and brain repair to learn more.
You can send a chat message (right side) on why you're using CBD and we'll send over research specific to that situation.
CBD should always be taken at least 4 hours away from medication and if you hold it under the tongue for up to 60 seconds, this can increase the bioavailability significantly. Work with your naturopath or doctor!
What about the type of CBD.
What's the best CBD to have positive effects
- First, we need CBD grown at an FDA registered farm in the US with organic hemp
- CO2 processed (cleanest option)
- 3rd party tested
- No pesticides
- No heavy metals
- No solvents
- No bacteria
- No mold
We like to test ours twice since the whole family uses it.
Then there's the question of CBD isolate (by itself) or CBD full spectrum.
We covered this in detail at our CBD isolate versus full spectrum review.
Here's the issue...roughly 40-60% of the population has histamine (allergy) issues.
This goes up as we get older and for women (thanks, Progesterone - see here)
We constantly see people have side effects to full-spectrum that completely go away with CBD isolate.
More importantly, all the research is on CBD by itself.
We also need to have enough CBD to match what the research is saying.
There's so much bogus (rip-off) product out there with 250mg or less per bottle.
You're better off buying hemp oil or just olive oil at that point.
Finally, there's a cost.
The key factor is cost per mg of CBD.
We price our 6000mg bottles (about 200 mg per dropper) at 2-3 cents per mg of CBD before discounts up to 30-50%.
We discovered CBD after a brutal perimenopause so we want people to be able to afford it.
Hopefully, you now have a good understanding of how CBD works in the body and brain.
It also sheds light on why we've spent 100's of hours writing 1 million+ words on it.
So fascinating that this tool is down here on earth to support our health.
Related Research:
The CBD and Anxiety Ridiculous Guide
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.