CBD versus CBG - Real Research

CBD versus CBG based on real research


 
We're starting to see a lot of popularity and just plain curiosity about all the cannabinoids.

 

Cannabinoids are the family of chemicals from cannabis that include THC, CBD, CBG, and more.

 

One of the most active areas of questioning is around CBD and CBG.

 

Below, we're going to really compare the two cannabinoids and dig deep into research.

 

We'll leave all the fluff to other sites.

 

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Here are the topics we'll cover: 

  • A quick intro to the endocannabinoid system
  • Key pathways that CBD and CBG affect
  • The big differences between CBD and CBG
  • CBD versus CBG for serotonin
  • CBD versus CBG for CB1 activity
  • CBD versus CBD for anxiety
  • CBD versus CBG for pain
  • CBD versus CBG for sleep
  • CBD versus CBG for appetite
  • Safety of CBD versus CBG

 

Let's get started!

A quick intro to the endocannabinoid system 

Before we jump into the players, let's look at the stage.

 

The endocannabinoid system itself!

 

We all have one and it's tasked with balancing other key systems: 

  • Nervous system - neurotransmitters like serotonin and GABA
  • Endocrine system - hormones 
  • Immune system - inflammation and cellular birth/death cycle
  • Opioid system - pain response, both physical and psychological

 

Almost every type of cell in the body has endocannabinoid receptors so it's clearly a big player in balancing just about everything.

 

We have two major cannabinoids that work in this system: 

  • Anandamide - the so-called "bliss" molecule
  • 2-AG - our baseline endocannabinoid

 

2-AG is like the ocean level (tides) while anandamide is called in when needed (and quickly destroyed) - like a wave of activity on the ocean.

 

The primary operate at receptors called CB1 (mainly in the nervous system) and CB2 (throughout the body with big impacts on the immune system.).

 

Sorry to go so deep into all this but it will pay off later when looking at CBD and CBG.

 

The cannabinoids, like CBD and CBG, are chemicals from the cannabis plant that is able to directly interact with this system above.

 

The two most prominent by far in the plant are THC and CBD: 

  • 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/

 

These ratios can fluctuate but just look at the difference.

 

If we really want to get beyond the hype, we have to look at pathways that they both affect.

Key pathways that CBD and CBG affect 

This is really a key place to focus.

 

What do CBD and CBG actually do in the body?

 

From there, we can then figure out how they will actually feel forgiven issues (anxiety, sleep, etc).

 

Here's the chart and don't worry, we'll break it down. 

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

 

So the big pathways for CBD: 

  • CBD supports anandamide function when low (by eating up FAAH)
  • CBD supports serotonin function (5HT)
  • CBD supports GABA function (key to anxiety and sleep)
  • CBD supports Glycine function (key to sleep and repair)
  • CBD supports various anti-inflammatory pathways such as GPR55, TRPV, and PPAR

 

As for CBG: 

  • CBG boosts anandamide levels (different from CBD which supports...we'll explain later)
  • CBG blocks one pathway of serotonin
  • CBG boosts adrenaline pathways
  • CBG supports anti-inflammatory pathways such as GPR55 and TRPV

 

Okay...so let's translate all this nonsense into something we can actually wrap our heads around.

 

Right off the bat, we can see some key differences here: 

  • GABA and Glycine - key calming agents - our brain's primary "brake" pedal
  • CBD has more effect on serotonin but is a support role
  • CBD supports anandamide while CBG boosts it
  • CBG boosts adrenaline function while CBD does not

 

We're going to look at what this actually means for health results.

The big differences between CBD and CBG 

So...what do we make of all this?

 

With 1 million+ words on CBD pathway research, let's go through our biggest differences in this order: 

  • Effect on anandamide between CBD and CBG
  • Effect on serotonin between CBD and CBG
  • Effect on GABA/Glycine between CBD and CBG
  • The adrenaline difference between CBD and CBG

 

They both show powerful anti-inflammatory effects although we like the  PPAR pathway that CBD drives.

 

Let's look at the real differences that matter.

Effect on anandamide between CBD and CBG 

Anandamide is a big deal.

 

Think of it a powerful backup call when stress, inflammation, trauma, or hyperactive immune response occurs.

 

Our body keeps it in a tight range but if you need an example of how it feels, just look at THC.

 

THC mimics anandamide and it boosts CB1 activity like a substitute.

 

Both the good and bad of THC (highs and anxiety/psychosis) come from boosting CBD 1 activity.

 

This is because it lingers too long and too strong at the CB1 receptors.

 

The role of anandamide is to keep us at just the right level of "high".

 

You know the feeling...where you're feeling pretty alright with the world.

 

CBD and CBG have very different effects in this powerful pathway.

 

CBG directly boosts CB1 activity (agonist).  It's sorta like discount THC in that respect.

 

That's why you see increased appetite and sedation.

 

Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021742/

 

We see this same effect with THC.

 

We don't see the "high" effect but there's not a lot of research on tolerance.

 

If you push a pathway like CB1 activity in one direction, the brain should push back by reducing natural levels of CB1 receptors and activity.

 

THC definitely does this which is why there can be withdrawal following long-term use.

 

CBD does NOT cause tolerance as its effect on CB1 activity is more nuanced.

 

Essentially, it eats up FAAH, which is the chemical in charge of breaking down anandamide.

 

This means that CBD kicks in when anandamide is running low but doesn't push it in one direction.

 

This difference is very powerful in terms of long-term use, tolerance, side effects, and more.

 

We don't see the appetite boost with CBD as a result.

 

Check out CBD for endocannabinoid deficiency.

 

If you're looking for the effect of CBG, PEA (cheap and safe) is probably a better alternative and it's much cheaper (get here).

 

We have a whole review on PEA here.

 

Let's look at a powerhouse player...serotonin.

Effect on serotonin between CBD and CBG 

Do not discount serotonin.

 

It's literally the master regulator of all human behavior.

 

It also directly controls the gut as well!

 

We have a big review of CBD and serotonin here with fascinating research.

 

One example…

 

A boost in serotonin will cause a person to reject unfair offers!

 

Okay...that's strange.  Check out Serotonin and self-esteem.

 

More importantly, serotonin is wrapped around: 

  • Pain (our threshold is governed by serotonin)
  • Anxiety - stress response is governed by serotonin
  • Depression - brain re-building chemical, BDNF, is governed by serotonin
  • Sleep - master regulator of the sleep process

 

Just about anything tied to mental health since it has its finger on the lever of brain repair/replenishment (BDNF) and dopamine - our reward circuit to name just two.

 

CBD and CBG have very different responses here: 

  • CBD acts as a feedback mechanism for 3 of the key serotonin pathways.
  • CBG blocks (antagonist) one serotonin pathway.

 

In our CBD and mental health review, you can see the effects of its action across almost every issue.

 

As for CBG, there's very little research, and based on the pathway effect above, we can piece out what it might do.

 

That specific pathway, called 5HT1A is important: 

5-HT1A receptor agonists are involved in neuromodulation. They decrease blood pressure and heart rate via a central mechanism, by inducing peripheral vasodilation, and by stimulating the vagus nerve. 

https://en.wikipedia.org/wiki/5-HT1A_receptor

 

In fact, key anti-depressant drugs work by boosting this pathway.

 

  • CBG reduces its activity (agonist).
  • That's likely why we see more mental health effects from CBD than from CBG.

 

One interesting aspect is that by slowing this pathway down, you get more adrenaline which probably speaks to that effect which we'll get into later.

 

Serotonin is also a big player in the gut.  Many of the anti-nausea drugs are essentially serotonin boosters.

 

We can use this pathway to confirm what we saw from the pathway chart: 

CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT. 

https://pubmed.ncbi.nlm.nih.gov/21243485/

 

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This makes perfect sense: 

  • CBD supports serotonin and therefore has an anti-nausea effect
  • CBG blocks serotonin and counters CBD's effect

 

Check out CBD and gut inflammation, CBD and nausea, or CBD and serotonin to learn more about this powerful pathway.

 

That's not a singing endorsement of CBG.

 

Let's turn to GABA/Glycine.

Effect on GABA/Glycine between CBD and CBG 

GABA is our primary "brake" pedal in the nervous system.

 

It's the main target for benzos if that's any indication of effects.

 

GABA has powerful effects on: 

  • Sleep
  • Anxiety 
  • Depression
  • OCD (all mental health issues really)
  • Pain - especially nerve-related
  • Seizures

 


The reason for a lot of this is that GABA had to keep glutamate (our "gas" pedal) under control.

 

Glutamate powers all brain activity but it's toxic if at excessive levels.

 

Literally kills brain cells (like red-lining an engine).

 

We have powerful systems to keep it balanced and the endocannabinoids system figures in strongly here.

 

CBD directly supports GABA function but with the feedback mechanism, we described above for serotonin.

 

This is important as you can see from the effects of increasing GABA levels: 

  • Calm
  • Sedated
  • Hypnotic
  • Amnesiatic
  • Anesthetic
  • Dead!

 

Benzos have an overdose risk (especially when used with opioids) but their predecessors, barbiturates, were even worse.

 

See CBD versus benzos or CBD and GABA.

 

We don't see these side effects (aside from calm) with CBD even at higher doses (tested up to 1500 mg).

 

That speaks to the feedback mechanism…..support when low.

 

Glycine is interesting and we expect it to gain popularity as people realize what it does.

 

It's a backup player for GABA as an inhibitory player in the brain and nervous system.

 

There's an immediate effect on sleep plus a range of different benefits that are finally coming to research.

 

We plan a deep dive on glycine shortly.

 

The net-net is this… 

  • CBD directly supports or "normalizes" GABA and glycine function
  • CBG does not appear to affect these pathways directly

 

In fact, CBG can have the opposite effect.

 

Let's go there now.

The adrenaline difference between CBD and CBG 

One item stands out as very different between CBD and CBG.

 

Adrenaline or the α2-AR pathway in the chart above.

 

Essentially, CBG boosts adrenaline function.

 

This is the sympathetic nervous system (fight or flight) response but also key for alertness, vigilance, focus, etc at lower levels.

 

Based on this, CBG may have a more revved-up effect compared to CBD. 

 
CBD has been shown to increase alertness during wake hours (see can I take CBD in the middle of the day) so it's more tied in with our natural clock. 

 

The net takeaway from this: 

  • CBD might be better if calm is the desired goal
  • CBG might be better for low energy

 

Keep in mind that revving the adrenaline engine as an agonist would likely build tolerance with longer use and reduce your natural function.

 

That's why we're such big fans of modulators (balancers) instead of agonists (boosters).

 

We don't want to end up worse than when we started (tolerance).

 

Alright...so we hit the highlights.

 

Let's finally bring this to a real-world (and real symptom) conclusion.

CBD versus CBD for anxiety 

CBD is the hand's down winner here.

 

We have lots of research on CBD and anxiety or CBD and mental health but by supporting both short and long term pathways, this really is its wheelhouse: 

  • Short term - GABA function (see CBD versus benzos)
  • Long term - serotonin function (see CBD versus SSRIs, CBD, and serotonin, CBD and BDNF)

 

As for CBG, it blocks one serotonin pathway and does not affect GABA.

 

So… 

The other main phytocannabinoids, including cannabigerol (CBG), cannabichromene (CBC) and cannabinol (CBN) (Fig. 1) [4,23], have been shown to exert antibiotic and anti-inflammatory properties, but have not been strongly associated with the behavioral effects of Cannabis; 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691841/

 

And more specifically: 

the recent discovery that CBG is a highly potent agonist for α2 adrenoceptor and a blocker of serotonin 5-HT1A receptor [24] underscores the potential importance of these and other alkaloids in the psychoactive profile of cannabis.

 

So it boosts adrenaline (wrong direction) and blocks serotonin (wrong direction).

 

No contest.

 

Its effect on anandamide may have some impact but CBD does the same thing.

 

What about pain?

CBD versus CBG for pain 

We looked at CBD's effect on pain in our CBD versus Tylenol article.

 

There is action in the opioid system but it's not as strong as THC (which reduces with time).

 

CBD's bigger impact is probably on inflammatory pain such as arthritis (see CBD and autoimmune).

 

That's the PPAR, TRPV, and GPR55 anti-inflammatory effects along with anandamide boosting and serotonin (pain threshold).

 

CBG also has anti-inflammatory responses (TPRV and GPR55) as well as anandamide effects but they mirror CBD for the most part.

 

There are only so many receptors to go around so overlap probably cannibalizes existing effects.

 

We're looking for the pathways that are different!

 

If CBG is a true booster of CB1 activity (discount version of THC), it should help with pain but again, any direct stimulation of CB1 (since it's critical) will likely lead to tolerance.

 

See CBD for THC withdrawals to learn more.

 

We much prefer the "modulator" approach to the "agonist" approach for CB1.  It's just too important to tamper with.

 

There are some studies on CBG and pain pathways but they date from the 1900s!

 

We want newer research that can take advantage of CRISPR technology and really understand what's going on.  

 

THC has powerful anti-pain effects but it comes with a price (tolerance).

 

This leaves you worse off than before you started with long-term use.

 

What about sleep?

CBD versus CBG for sleep 

We have quite a bit of research at our CBD and sleep review but it's pretty self-explanatory.

 

Guess what pathway most anti-insomnia drugs affect?

 

GABA!

 

Histamine is also another key area which we'll touch on below since CBD calms histamine response (the type of CBD really matters).

 

GABA is key to calming nervous system activity and sleep.

 

CBG doesn't have much (if any) research on sleep but one thing is clear...adrenaline is the enemy of sleep.

 

In fact, it's the main driver of the "fight or flight" setting where we're more interested in "rest and digest".

 

That's GABA and acetylcholine (see acetylcholine here).

 

Glycine is also a big player in sleep function: 

Research shows oral glycine elevates serotonin, reduces symptoms of insomnia, and improves sleep quality. Other studies suggest it may help you bounce back to healthy sleep cycles after a period of disrupted sleep.  

https://www.psychologytoday.com/us/blog/sleep-newzzz/201902/4-sleep-benefits-glycine

 

Did you catch that serotonin mention in there?

 

Serotonin is made from glycine so it comes full circle since CBD boosts glycine (the raw production) and normalizes serotonin (the big player).

 

CBG blocks serotonin and boosts adrenaline.

 

For sleep, it's clearly CBD.

 

CBG might be good for the opposite desired effect when you can't get going but again, watch out for tolerance since it's an agonist.

 

Not for long-term use.

 

One interesting caveat...appetite.

CBD versus CBG for appetite 

Just to show how powerful the above pathways are, let's look at appetite...a complicated blend of hormones, neurotransmitters, and metabolic/energy complexity.

 

Not to mention gut microbiome activities from trillions of bacteria!

 

CBD has no real impact on appetite (see will CBD make you hungry).

 

CBG on the other hand has a direct boost to appetite even if you've already eaten!

 

This can actually be important in situations like chemo, or various wasting illnesses as an alternative to THC which also has the same effect.

 

CB1 activity is at the root of this effect when you boost it directly: 

It is now confirmed that endocannabinoids, acting at brain CB1 cannabinoid receptors, stimulate appetite and ingestive behaviors, partly through interactions with more established orexigenic and anorexigenic signals.  

https://pubmed.ncbi.nlm.nih.gov/16148436/

 

It's body weight as well...even with the same caloric intake and activity.

 

CB1 is powerful.

 

THC directly spikes its activity while CBG boosts its activity (agonist).

 

CBD doesn't directly interact with CB1 receptors but supports anandamide (the primary CB1 agent) when low.

 

That's a big difference and appetite is only one effect amount 100's if not 1000's across the body.

 

The appetite effect is just a confirmation of this activity but an important one.

 

So...outside of appetite boosting and adrenaline support, CBD appears to be the better candidate.

 

You wouldn't think so judging by all the "Is CBG the new CBD?" headlines.

 

Now, you know better.

 

As you can see, we do everything based on research and if we saw a clear advantage to CBG or even a value proposition, we would not offer it...we would be taking it!

 

That brings up a question...why not take it?

Safety of CBD versus CBG 

We have lots of research on CBD safety (see CBD safety here).

 

It's been much more thoroughly vetted along with THC since they are the dominant cannabinoids in cannabis.

 

There's very little research on CBG safety in NIH studies.

 

Long term, we don't want anything that pushes a key pathway in one direction (agonist).

 

The two items of concern with CBG would be: 

  • Adrenaline pathway agonist
  • Serotonin blocker
  • CB1 activity

 

If you look at the original chart, we want more "modulators" and less "agonists, antagonists" for long-term safety.

 

Especially on such far-reaching pathways as serotonin and CB1 (the entire body, really).

 

We'll look forward to more research and less marketing spin over the next few years.

 

For appetite and lethargy, CBG might be interesting as an alternative to THC.

 

For CBD, learn all about why CBD isolate is so different from full-spectrum especially when it comes to histamines and affordability.  

 

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

 

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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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