Goodness...the alphabet soup of it!
There's a lot of talk (and marketing) around the different cousins of cannabinoids with these three getting the most attention since they don't fall under the same scrutiny that THC does.
We did a major review of CBD versus CBG but let's bring in a slightly different player...CBN.
CBN is slightly different than the other two in how it works and where it works.
Interestingly, if it's being pitched as part of full-spectrum, good luck with that.
Only trace amounts show up in the natural plant and that's also true for CBG.
We'll break down the typical levels below.
Here are the topics we'll cover:
- Intro to the endocannabinoid system
- Key pathways of CBD versus CBG versus CBN
- CBD versus CBG versus CBN for sleep
- CBD versus CBG versus CBN for pain
- CBD versus CBG versus CBN for mental health and addiction
- CBD versus CBG versus CBN for inflammation
- Research differences between CBD, CBG, and CBN
- Safety differences between CBD, CBG, CGN with a focus on tolerance
- The Full Spectrum versus CBD isolate debate
Let's get started!
Intro to the endocannabinoid system
We first need a lay of the land.
All three cannabinoids work within our endocannabinoid system.
This system dates back about 600 million years ago evolutionarily speaking and we share it with all animals.
It is tasked with balancing (called homeostasis) other key systems:
- Nervous system - neurotransmitters and brain function
- Endocrine system - hormones, both metabolic and steroidal
- Immune system - inflammation and cellular birth/death cycles (key to cancer)
The beauty of supporting the endocannabinoid system is that we can offer a feedback effect rather than just push a pathway up or down in one direction.
For example, serotonin is our master regulator of all human behavior.
- Too little can display itself in depression, anxiety, risk-taking, etc
- Too much of it can lead to agitation, insomnia, and worse
It's all about balance.
SSRIs (antidepressants) push serotonin up in one direction until the body pushes back (called tolerance). See CBD versus SSRIs or how SSRIs really work
We've covered in detail how CBD is able to support serotonin when low (due to pain, stress, trauma, etc) but not when high (no serotonin syndrome noted in side effects).
This is the single greatest aspect of cannabinoids.
All three cannabinoids affect this system but in different ways.
Let's introduce a few technical terms which will help and we'll look at what this means practically speaking.
- Agonist - boosts activity in one direction
- Antagonist - reduces activity in one direction
- Negative or positive allosteric modulator - feedback response depending on the state of the system
- Inhibitor - blocks activity (similar to antagonist but more pronounced)
Okay...so why go back to science class?
So you can really understand the differences between CBD, CBG, and CBN without the marketing hype that currently dominates the market.
Let's go there now!
Key pathways of CBD versus CBG versus CBN
First, remember how we said the levels were very different in the plant?
- Phytocannabinoid
- Content
- Cannabidiol (CBD)
- 17.9%
- Δ9-Tetrahydrocannabinol (Δ9-THC)
- 1.1%
- Cannabichromene (CBC)
- 1.1%
- Cannabigerol (CBG)
- 0.2%
- Cannabinol (CBN)
- Traces
- Cannabidivarinl (CBDV)
- Traces
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/
Of course, these levels can differ depending on the strain with most focus on THC but looking at the legal hemp market (less than .3% THC), CBN and CBG are still very small.
That brings up a good point, the law specifically set a ceiling on THC but not the other cannabinoids (with THC8 still in debate).
CBD, CBG, and CBN can all be part of legal hemp-derived products sold in the US.
Now let's look at the pathways which will really help later:
The chart is here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/
There are key pathways that endocannabinoids work with:
- TRPV - key to sensory responses, pain, and more
- CB1/Anandamide - a primary type of receptor throughout the body
- Serotonin (5HT) - master mood regulator
- GABA - the brain's "brake" pedal - key to sleep, pain, and anxiety
- Glycine - a backup "brake" to GABA - powerful effects on sleep and collagen
- PPAR - a powerful anti-inflammatory channel
- Opioid system - key to pain sensitivity, both physical and psychological
- Adrenaline - alertness but also panic across a scale
- Adenosine - key to sleep
- GPR's - various pathways with newly discovered effects across mental health and inflammation
Okay...that's a lot of jargon. Don't worry, we'll look at what this means practically but it's important to start with science rather than hype.
What can we see right away across the three cannabinoids?
- CBN boosts TRPV and anandamide (CB1 agonist)
- CBG boosts adrenaline, TRPV, and anandamide and reduces serotonin and GPR55 (see GPR55 for more)
CBD?
Well…
- CBD balances (modulator) serotonin
- CBD balances (modulator) GABA
- CBD balances (modulator) glycine
- CBD balances (modulator) opioid system
- CBD supports anandamide (bliss molecule)
- CBD supports TRPV
- CBD supports PPAR
See why we focus on CBD? It's research. All research.
So...let's actually turn this into practical effects and differences between CBD, CBN, and CBG.
We'll hit the main reasons for which people use cannabinoids.
Starting with sleep.
CBD versus CBG versus CBN for sleep
The big players with sleep are GABA, Glycine, and Serotonin.
We'll start with the immediate player on sleep RIGHT NOW!
CBD versus CBN versus CBG for GABA and sleep
GABA is literally the brake pedal of the brain and nervous system...literally the target of benzos (CBD versus benzos) and sleep meds like Ambien (see CBD versus Ambien).
We don't want to push it in one direction or we can get tolerance which is what happens with both those classes of meds.
So...what about our big three?
CBG actually supports adrenaline which is in the opposite direction. This might be more for an inability to wake up.
Adrenaline is the key player in our fight or flight system which is the opposite of rest and digest.
CBN is a bit different.
You can think of CBN as discount THC...it's actually the chemical precursor to THC in the cannabinoid family.
In this respect, it's able to boost CB1 activity which is where anandamide works.
Anandamide is basically like a big wet blanket across pathways including brain excitation.
In this respect, it will slow GABA function:
AEA shortened the duration of RSNA inhibition, suggesting a possible presynaptic inhibition of glutamate release previously obscured by a more dominant GABAA effect
https://journals.physiology.org/doi/full/10.1152/ajpheart.00870.2003
To translate, anandamide boosts GABA and blunts glutamate (the gas pedal).
This is good and bad for sleep...similar to THC's effect.
By pushing anandamide-like function in one direction, it will benefit sleep in the short term.
Long term, the brain doesn't like this type of interference and will actually push back by reducing CB1 receptor numbers and sensitivity.
CBN should have less effect along this tolerance pathway than THC (which is stronger) but the same theory applies.
CBN may be mildly psychoactive (the "high") as well due to this same effect.
Long term, we don't want to slowly erode the very pathway we're trying to support.
Then there's CBD:
preliminary clinical trials suggest that high-dose oral CBD (150-600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia, and epilepsy,
https://pubmed.ncbi.nlm.nih.gov/24281562/
We can see from the table above that CBD is a positive allosteric modulator of GABA.
This means that it boosts GABA when low but not when high.
We know this because, at very high doses, it doesn't follow the trajectory of benzos with dosage:
- Calm
- Sedated
- Hypnotic
- Amnesiatic
- Anesthetic
- Dead!
Benzos can cause death by literally slowing things to a stop (including breathing) although this is more common in conjunction with other sedative drugs like alcohol or opioids.
CBD doesn't have this ever-ratcheting effect with dosages tested up to 1500 mg.
CBD also supports anandamide function but again, as a modulator. For this reason, we don't see the high (too much CB1 activity) or tolerance with time.
See why we get excited?
What about glycine?
CBD versus CBN versus CBG for glycine and sleep
You probably haven't heard of this simple amino acid (the most simple actually) but you'll want an introduction if sleep is an issue.
You can supplement it (buy here) but we have a full review here.
Basically, glycine activates the "trigger" for falling asleep. It works like a backup inhibitory player to GABA and actually manages glutamate (the opposing gas pedal).
CBN and CBG do not have research on supporting glycine.
CBD is an allosteric positive modulator which is the same feedback mechanism as with GABA.
Support when low!
Glycine is also key for collagen formation with skin, bones, and ligaments.
Let's look at our master regulator for sleep..serotonin.
CBD versus CBN versus CBG and serotonin for sleep
Serotonin is a key player and "shaping" sleep:
While serotonin seems to both induce sleep and keep you up, it's a chemical precursor to melatonin, the main hormone involved in sleep.
https://www.healthline.com/health/dopamine-vs-serotonin
That's right...melatonin is rate-restricted by your serotonin levels.
Again...it's all about balance with serotonin. Too little and you can't get out of bed. Too much and you can't fall asleep.
See CBD and serotonin to learn more.
Interestingly, CBG is an antagonist for one pathway of serotonin. It reduces its level.
CBN does not appear to directly affect serotonin.
CBD is a negative allosteric modulator...again...feedback mechanism.
We go through lots of studies on how CBD will support serotonin when it's exhausted by pain, stress, infection, etc.
We'll look at one in the pain section below specific to CBD.
Again, we have lots of research on CBD and this pathway but very little on CBN or CBG.
Since CBN works a bit like THC, it might boost that pathway but in one direction (no feedback).
We don't want that either as it draws down natural serotonin function like SSRIs (see CBD versus SSRIs) antidepressant.
So net net…
- CBG is probably stronger for staying awake (adrenaline)
- CBN can support sleep short term but not great long term (tolerance)
- CBD has a feedback response to support sleep
Also, check our master review of CBD and sleep and well as Vitamin D and Magnesium glycinate reviews.
Speaking of pain (which can greatly interfere with sleep)!
CBD versus CBG versus CBN for pain
A few key pathways to look at:
- Opioid system - master regulator of pain signaling
- Anandamide - powerful pain suppressing pathway in the endocannabinoid system
- Inflammation - key source of many types of pain especially neuro or systemic inflammation
- COX2 - directly player in the pain system (NSAIDs work here - see CBD versus NSAIDs)
- Serotonin - pain sensitivity manager
So...how do the 3 cannabinoids work here?
Let's walkthrough.
The opioid system is actually more complicated than you might expect.
We think of it as just a pain suppressor but really, it's tied into our basic systems as both the carrot and the stick for behavior.
This system is a perfect example of the tolerance we've been ranting about above.
The opioid crisis is literally this effect (plus addiction) writ large.
When people take external opioids, their natural system reduces opioid production.
You're left worse off than when you started over time.
Eventually, you're just taking opioids to not feel horrible (as opposed to feeling good).
CBD is an allosteric modulator which means it functions in the normal feedback mechanism.
This is so important...we don't see addiction or tolerance with CBD as a result.
The goal (and effect) is to "rescue" opioid function when exhausted.
CBG and CBN do not have direct studies of effects on this system.
That being said, CBN boosts anandamide and it's tied into everything!
We can expect a THC-like effect on pain as a result but again, long term, this has a tolerance potential since it boosts CB1 activity in one direction (although not as strongly as THC).
In fact, pain is one of the areas where CBN may be strong in the short term. Long term, not great.
We also see the correlation with an appetite as both THC and CBN increase appetite.
Check out CBD versus THC to really learn about that cousin!
Speaking of anandamide (main target for THC and CBN).
CBD versus CBG versus CGN for anandamide and pain
We looked at anandamide in detail at our CBD and endocannabinoid deficiency review.
Again, it's basically a reserve backup when other systems are overwhelmed and this includes pain (opioid, serotonin, inflammation, etc).
This is at the heart of CBN's effect (albeit, in one direction).
CBG has much less effect (partial agonist).
CBD works as a feedback mechanism by eating up FAAH, the chemical that breaks down anandamide.
A great example of anandamide's power can be seen by our review of the woman who can't feel pain (or anxiety or depression for that matter).
Basically, she doesn't make FAAH due to a genetic variation.
This is very rare as it's actually quite dangerous. She won't know her arm is on fire until she smells it (actually has happened in cases).
FAAH will probably be one of the first targets of CRISPR gene editing.
If we can dial down FAAH...say 15%...goodbye chronic pain (and anxiety and depression, etc).
Remember that FAAH works against anandamide so that shows you how powerful anandamide is with pain.
- Short term, CBN has a more powerful effect there (not as powerful as THC).
- Long term, the feedback mechanism of CBD is better since it doesn't cause tolerance.
A whole subset of pain comes directly from inflammation. Let's go there.
CBD versus CBN versus CBG for inflammatory pain
IBD. Rheumatoid arthritis. Colitis. The list goes on and on.
Pain with a root in inflammation.
This is where PPAR comes into play although anandamide and serotonin are involved everywhere.
PPAR is a powerful anti-inflammatory pathway:
Activated PPARs regulate the inflammatory response through their ability to regulate the expression of several genes that are involved in inflammation.
https://www.nature.com/articles/nri912
We can see from our chart the following:
- CBD boosts PPAR activity
- Very little research ties CBN and CBG to PPAR.
CBN should have an effect there since THC does but it's just not well researched.
To learn why this is important, check out:
- CBD and neuroinflammation
- CBD and rheumatoid arthritis
- CBD and IBD or IBS
- CBD and gut inflammation
Let's zero in one on a particular (but well-traveled) piece of this inflammatory pathway.
COX2 and prostaglandins.
COX2 and prostaglandins: CBD versus CBG versus CBN
COX2 is probably familiar to you only with the medications that directly counter it:
- NSAIDs like Ibuprofen, Advil, and Motrin (CBD versus NSAIDs)
- Tylenol and it's class of meds (see CBD versus Tylenol)
- COX2 inhibitors like Celebrex
Basically, COX2 is a big signaller of pain in the body. It's directly tied to the inflammation process.
You see this most prominently with PMS.
Essentially, a class of inflammatory agents called prostaglandins are tasked with breaking down the uterine wall.
Unfortunately, they also trigger COX2 pain signaling with this process which is the pain associated with PMS and a range of issues.
PPAR is critical in countering this pain signaling:
Our results demonstrate that Cox2 can be up and downregulated during endotoxin tolerance in astrocytes, and PPAR agonists might be effective for controlling this target under conditions of multiple proinflammatory stimulations of brain tissues with endotoxin.
https://link.springer.com/article/10.1134/S0006297915100065
To translate, things that boost PPAR can help wrangle in COX2 activity especially when under inflammatory stress.
Check out CBD and PMS or PMDD or the versus Tylenol or versus NSAIDs for more.
Let's turn to serotonin...one of our favorites.
CBD versus CBG versus CBN for serotonin and pain
Pain is really an influencer of behavior (don't do that...it hurts!) in the truest sense of the word.
If that's the case, it's in serotonin's wheelhouse.
Indeed, serotonin acts as a pain sensitivity adjuster.
A fascinating study looked at injury-induced chronic pain, serotonin, and CBD's effect there:
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/
To translate:
- CBD "rescued" serotonin (5hT)
- CBD reduced anxiety (remember that pain can be psychological as well)
- CBD reduced pain sensitivity (analgesia)
Our favorite word there is "rescue". Not boosted or reduced. Rescued when low.
CBG actually reduces serotonin in one pathway.
CBN should have some impact on serotonin (upward) via its CB1 activity similar to THC...albeit in one direction (no feedback).
Again, short-term, CBN. Long-term CBD.
Serotonin is a great jump point for mental health and addiction.
CBD versus CBG versus CBN for mental health
These are the pathways we'll focus on for mental health:
- Serotonin and other neurotransmitters (GABA, dopamine, etc) balance
- BDNF - our brain's fertilizer and the most important player you've never heard of
- Stress response
- Neuroinflammation and oxidative stress
Okay...that's a bunch to cover but it touches on everything in the brain.
Let's get started.
CBD versus CBG versus CBN - Serotonin and other neurotransmitters
We've covered serotonin already above because as we said, it's the master regulator of all human behavior.
Check out our review of serotonin here or serotonin and self-esteem.
You can find connections with serotonin being too high or too low and pretty much every mental health issue plus addiction.
Addiction makes sense once you see the original use as a response to key neurotransmitter pathways not function correctly.
Self-medication. See CBD and addiction or CBD and mental health to really go deep.
Our focus here is on mood. Serotonin is the master switch for:
- Depression
- Anxiety (stress response)
- Impulsiveness
- Eating and personality disorders
That's just a sampling.
The tricky part is that we can just boost or reduce it. It needs to function in a tight range as there are issues on both sides of that range.
Looking at CBD versus CBG versus CBN, we see very different responses.
CBG actually reduces serotonin in one direction (antagonist on our chart).
CBN doesn't have much effect on serotonin aside from its anandamide connection.
CBD acts as a direct feedback mechanism on serotonin...supports when low but not when high and actually decreases when too high (negative modulator).
A few examples.
Depression and CBD:
In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment.
https://pubmed.ncbi.nlm.nih.gov/26711860/
To translate...CBD boosted serotonin in the prefrontal cortex (key area for depression) DEPENDENT on the initial state.
Meaning, if a person was depressed, they experienced more serotonin support.
Check out CBD and depression to learn more.
There's lots of research that dives into this. We go into what is exactly eating up the prefrontal cortex's "connectivity" which is key.
Interestingly, serotonin also manages dopamine, our reward circuit player.
We did a big review on CBD and schizophrenia since dopamine imbalance is key there.
It's tricky because dopamine is too high in one brain area (striatum) and lower in another (the same prefrontal cortex above).
The common antipsychotics pound dopamine levels to bring down the "positive" side effects like hallucinations and paranoia but do little for the "negative" effects like depression and low effect (prefrontal cortex again).
The results with CBD were impressive.
The balance between GABA and glutamate is critical as well for anxiety, OCD, PTSD, panic attacks, repetitive thoughts, etc.
We have breakouts on all of those and more from our mental health review.
As for CBG and CBN, there's just less research.
Anandamide is a big player so we would expect to see some benefits (short term) from CBN since it boosts anandamide.
Tolerance effects are eventually an issue due to the direct boosting.
CBG might be good for lethargy, catatonia, or any issue where the nervous system isn't able to "wake up" due to the adrenaline impact.
The reduction in serotonin pathways is not ideal.
Downstream from serotonin, there's a very big player to look at which may the key to addiction and mental health.
BDNF!
BDNF - CBD versus CBG versus CBN
Our brain's fertilizer. This is really becoming the go-to for current research in all things brain-related.
There are so many assaults upstairs:
- Stress
- Hyperactive immune response
- Chemical, drugs, and meds
- Excessive glutamate
- Oxidative stress
- Escaped bacteria or viruses from the body (hello gut barrier!)
The offsetting factor?
BDNF (and it's family of neurotrophins).
We did a deep dive into how SSRIs actually work (until they don't due to tolerance) and the secret?
BDNF.
Exercise and mindful meditation? BDNF.
Goodness.
So...what about CBG versus CBN versus CBD.
We have to focus on serotonin here. By the way, estrogen boosts serotonin so when it goes (monthly or around the late '40s), there goes BDNF!
Hence the increased risk for mood issues and dementia.
CBG showed a partial effect from studies on Huntington's:
We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322067/
The study attributed this to PPAR which just shows how interwoven all these pathways are.
As for CBN, CB1 receptor activity does support BDNF.
Interestingly, BDNF also boosts our natural endocannabinoids...a virtuous cycle.
We don't see direct research on CBN and BDNF which is just a function of less research in general.
In terms of addiction, there are two critical pieces that determined relapse.
The first was BDNF levels (which should be front-page news) and the second?
Stress.
Stress response
This is a big one for mental health and the endocannabinoid system is a big player in rebalancing.
Here are the key pathways:
- Serotonin - first responder to stress
- Anandamide - our primary backup stress responder
- GABA - the offset to cortisol and brake pedal
- Acetylcholine- the rest and digest player
Okay...we've covered a lot of this.
Serotonin and anandamide are really big responders to stress.
In fact, in many mental health issues, you'll see serotonin depleted (exhausted) and anandamide elevated (trying to call the reserves).
Serotonin drives BDNF (brain repair) while anandamide acts like a big wet blanket...on stress in this case.
The two big stress players are cortisol and corticotrophin-releasing factor.
The latter initiates the whole stress response (see CBD and CRF for more).
- CBD, CBG, and CBN all support anandamide
- CBD supports serotonin.
- CBG partially reduces it.
- CBN has no direct effect.
CBG and CBN may still have some benefit by supporting anandamide although they do it in a direct way which can lead to tolerance.
GABA is the main target for benzos (see CBD versus benzos), the main medication class for anxiety and stress.
Yes, they're highly addictive and build up brutal tolerance very quickly but they directly target GABA.
CBD supports GABA when slow (see CBD and GABA). The other two probably indirectly boost it via anandamide.
After all, anandamide is named after the Hindu goddess of bliss, Anand!
Again...a subtlety in how the pathways are affected.
GABA is key to anxiety, OCD, depression (from too much anxiety), pain, sleep, and more.
Guess what other chemical directly drives GABA? Alcohol (see CBD versus alcohol or is CBD better than alcohol).
Again, tolerance issue there but now you know why it's the most popular drug of choice (with a hit to serotonin as well).
We've looked at all of those in detail along with other tools.
Finally, acetylcholine.
This is a fascinating player in mental health.
Acetylcholine has both a calm and focused effect at the same time!
It's the reason some people (self-medicating) crave nicotine (see CBD for nicotine addiction).
- Anandamide is known to support/manage acetylcholine function so all three should have some effect here.
- Acetylcholine is the key to dementia by the way. You can supplement choline to support this pathway easily. See acetylcholine review.
Let's turn to inflammation in the brain.
Neuroinflammation and oxidative stress
All the new research is on the immune system's effectiveness on mental health.
That's inflammation!
We'll include oxidative stress in the mix. In fact, most mental health issues show elevated inflammation in the nervous system.
We covered this in detail at our CBD and neuroinflammation.
What about CBD versus CBN versus CBG.
These are the pathways there:
- PPAR
- Glutathione
- Microglia activation
There are others but these are big hitters.
First, we know that PPAR is a powerful inflammation circuit in the body and brain.
Remember how stress was key to mental health?
PPAR's effect:
PPAR–α activation has been shown as a natural response to stress, having the ability to mediate and modulate the stress response (Hillard, 2018
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190882/
All three will support this pathway via anandamide but CBD directly supports it.
Let's turn to our primary detox and anti-oxidation pathway...glutathione.
This is a big player in keeping the energy-hungry environment of the brain under control.
Oxidative stress is the enemy of the brain.
One (of many examples):
Reduction of plasma glutathione in psychosis associated with schizophrenia and bipolar disorder in translational psychiatry
https://www.nature.com/articles/tp2017178
So...CBD versus CBG or CBN?
CBD:
Thus, CBD protects lipids and proteins against oxidative damage by modulating the level of oxidative stress, which participates in cell signaling pathways.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
In fact, it's more powerful than Vitamin E or C...the mainstays for supporting glutathione.
See CBD and oxidative stress or CBD and glutathione.
CBG appears to have a partial effect as well:
Taken together, our in vitro results showed that CBG is able to counteract oxidative stress by activation of CB2 receptors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289301/
CBN should exert similar effects via CB1 activity.
Okay...we need to move on eventually!
Check out CBD and mental health to learn all about different aspects.
CBD versus CBG versus CBN for inflammation
We just wrapped on inflammation and mental health but inflammation is critical across the body.
We'll zoom in on gut inflammation, cancer, and autoimmune since they're at the heart of most things that ail us now.
Let's start where most issues probably start...the gut.
If you think about it, the gut is our weakest point...where the outside world gets inside.
The fact that we can protect against trillions of bacteria, viruses, and fungi trying to get in is a testament to this beautiful system of walls, sentries, and even neurons!
Yes, our second brain...the most neurons outside of the brain.
Inflammation is deadly as it breaks the gut barrier and allows these interlopers into our body and brains where our immune system wages war.
Hello, autoimmune. Hello, dementia. Hello, brain inflammation.
So...what does research show for CBG, CBN, and CBD for these elements.
All have impacts on the immune response (inflammation).
Let's start with CBG.
Let's look at studies on CBG and colitis (mouse model) which is a brutal disease characterized by gut inflammation:
The CB2 receptor pathway was also found to modulate the favorable effects of cannabigerol (CBG), a non-psychotropic cannabinoid capable of reducing nitric oxide production in macrophages and attenuating murine DNBS-induced colitis in both a preventive (pretreatment) model and therapeutic (established colitis) model
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038810/
Let's break this down.
Basically, CBG slowed the inflammatory response to both prevent and help with existing colitis.
CB2 is the endocannabinoid receptor that's prevalent in the immune system so this makes sense.
There's less research on CBN and gut inflammation but THC has studies so we can expect a similar reaction since CBN is just THC before being oxidized.
CBD's effect on gut inflammation is pronounced.
We've covered it in CBD and gut inflammation or CBD and leaky gut but one example following the introduction of c diff (nasty bacteria rampant in hospitals).
Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.
https://pubmed.ncbi.nlm.nih.gov/29238589/
Let's translate.
C diff causes an explosion of inflammation which breaks down the gut barrier between us and the outside world.
CBD offset these effects and protected the gut cells from dying (apoptosis).
Since CB1 was in play, we can assume CBN and CBG also have similar effects.
This gut inflammation status and the barrier are important for autoimmune.
Why is the immune system suddenly attacking joints (Rheumatoid arthritis) or islet cells (diabetes)? Why so specific?
We cover this in our CBD and autoimmune review (as well as RH or diabetes breakouts).
Protein mimicry.
Essentially, there are small segments of RNA or proteins in the attacking bacteria/virus that mimic that found in our own cells.
The immune response to this "mistaken" bacteria signature is the root of autoimmune.
The inflammatory response is critical in terms of how cannabinoids work.
Let's zero in on the little inflammatory assassins called cytokines.
CBG:
LPS-stimulated RAW 264.7 macrophages induced the expression of the pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ. CBG pre-treatment reduced the protein levels of the pro-inflammatory cytokines.
To translate (please), introduction of bacteria (LPS) caused inflammation to spike. CBG reduces this effect. This applies equally to autoimmune where the immune system is "stuck" on.
Two birds with one stone:
CBD, CBN, and THC each suppressed P. gingivalis-induced IL-12 p40, IL-6, IL-8, and TNF release while enhancing the anti-inflammatory cytokine, IL-10, from human innate cells.
https://www.frontiersin.org/articles/10.3389/fimmu.2019.02288/full
So, CBD and CBN (discount THC) both countered inflammation from gingivitis.
Look...all the cannabinoids calm the immune response. That's part of the role of the system.
The difference?
CBN, like THC, will push down the immune response in one direction. CBG likely does the same.
CBD works in a feedback way.
That's a big difference!
Let's look at this.
Differences between CBD, CBG, and CBN with a focus on tolerance
Clearly, there's some carryover between the three cousins (similar to genetic similarities among siblings).
The big difference (aside from the amount of research) is the method of action.
Stay with us because it's the reason we've done 1 million+ words on CBD research.
99% of medications, supplements, and even cannabinoids have one thing in common.
A basic flaw.
They push a given pathway up or down in one direction.
- Benzos boost GABA (causes tolerance)
- SSRIs boost serotonin (causes tolerance)
- Nicotine boosts acetylcholine (cause tolerance)
- Opioids boost endorphins (causes tolerance)
- NSAIDs suppress COX2 (causes tolerance and knock-on effects on heart/gut)
We could go on and on and on.
The body/brain doesn't like outside influences on critical pathways since they hit like a hammer.
THC boost CB1 activity to mimic anandamide.
With longer-term use, the body will actually reduce CB1 receptor numbers and sensitivity.
This means less anandamide or "bliss" over time.
That's tolerance and it's the basis for withdrawals.
What about CBD?
Here's a perfect example of the powerful example:
- Healthy cell with low inflammation - CBD has no effect
- Healthy cell with high inflammation - CBD reduces inflammation
- Cancerous or virally infected cell - CBD INCREASES inflammation
Read that back over because it's the whole reason we've written over 1 million words on it.
The 3rd result makes more sense once you understand that this is how our body gets rid of awry cells.
Radiation and chemo are just giant boosts of oxidative stress (inflammation).
We see this same effect across every pathway we study.
THAT's the difference between CBD, CBN, and CBG.
CBN and CBG are agonists (boost) or antagonists (reduce).
They're not modulators (different results depending on the state of the system).
Short term, it's probably fine (as with THC).
Longer-term...over a period where we can actually get benefits...that's the wrong way to go.
This is probably more an issue with CBN than CBG but both function in this way.
This brings us to safety.
Safety differences between CBD, CBG, CGN
There's pretty good research on CBD and safety:
- CBD safety
- Can you take CBD long term
- CBD and medications
There's very little research on CBG and CBN in terms of safety.
Longer-term, we would expect the tolerance effects from above but we just don't know.
CBN may share watered-down effects similar to THC in terms of cognitive function but again, very little research.
The downside to agonist/antagonist/inhibitors (one-direction effects) is that all our pathways have multiple effects.
If we're pushing immune function downward, that can leave us susceptible to infection and/or cancer.
That's why the 3 result example above is so important with CBD.
All three will likely have the same requirement with medications to be taken at least 4 hours away since they rely heavily on the p450 liver processing pathway that 60% of meds require.
Always work with your naturopath.
At the levels naturally found in cannabis (trace levels), CBG and CBN are probably fine.
Our focus is more on products that add concentrated amounts back into a product.
We just don't have good research on that front although we've looked at the underpinnings of how that might work above.
The Full Spectrum versus CBD isolate debate
A big sales pitch for full-spectrum is that you have all the cannabinoids in there including CBG and CBN.
It's usually added to hemp oil as well.
If the levels are as in the plant, they're probably low (remember that CBD and THC are the primary cannabinoids by level naturally).
Some products may reflect hemp strains with higher CBG/CBN levels or have isolate added back into the final product.
A few notes.
First, there's the issue with histamine.
We focus on clean CBD isolate and MCT oil from organic coconut oil for this reason.
Roughly 40-60% of the population has histamine issues.
This goes up for women (thanks, progesterone) and as we get older.
The last thing you want to do is introduce lots of plant material to the mix.
The side effect profile for broad-spectrum and full-spectrum CBD is very different than CBD isolate as we originally found out the hard way (that story is here).
We tried 3-4 of the biggest full spectrum brands (CBD, CBG, and CBN) and had the characteristic allergy or histamine responses.
CBD isolate was completely different. Those side effects were gone.
Histamine is excitatory in the brain so that's the wrong direction for sleep and calm (the two biggest reasons people use cannabinoid products).
There is one place where CBN has an advantage over the two others….appetite!
Both THC and CBN are able to increase appetite which is a very specific effect not shared by CBD or CBG.
Beyond that, CBD has the greatest "reach" in terms of pathways and that's why we focus our energy there.
We'll look forward to more definitive research in the meantime.
Be well. Take care of each other. Take care of yourself.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.