What Do We Know About CBG?

What Do We Know About CBG?

What Do We Know About CBG?

By Jason Wilson, MS

Cannabigerol, or CBG. The buzz is building rapidly, and some are calling it “the new CBD.”

As consumers begin to turn to CBG as an alternative or complement to CBD, it is important to review the current scientific landscape around CBG research. What do we actually know about CBG? Does it behave similarly to CBD? Is it safe? In this article we will briefly explore the history and current state of the science of CBG.

Before we begin, I’ll first recommend a great chapter from Handbook of Cannabis and Related Pathologies, where much of this information was sourced. Chapter 99, Potential Medical Uses of Cannabigerol: A Brief Overview (2017) is a fantastic shortcut to getting caught up on most of the research surrounding CBG. (Deiana, 2017)

What is CBG?

Cannabigerol, or CBG, is a cannabinoid found in the Cannabis plant, like CBD or THC. It is found primarily in its acidic form, cannabigerolic acid. This form of CBG is unstable and decarboxylates to form CBG. One thing that is particularly interesting about CBGA is that it is the chemical precursor to THCA, CBDA, and CBCA. Without CBGA, the Cannabis plant will not produce those traditional cannabinoids. In fact, some researchers are actively experimenting with CBG knock-out plants which do not form any cannabinoids! Typically, CBG appears in very trace amounts in the Cannabis plant. However, thanks to modern breeding practices, CBG-rich Cannabis cultivars are now available to farmers.


CBG was characterized in the Cannabis plant roughly around the same time that THC was identified as the intoxicating component of the plant, in the mid 1960s. (Mechoulam, Gaoni, & Hashish, 1965) Significant research into CBG did not pick up until the early 2000s. Now this lesser-known cannabinoid is gaining in popularity in the hemp markets, primarily because CBG dominant varieties of Cannabis often have even lower THC levels than CBD dominant varieties of Cannabis, making it easier for hemp farmers to pass their state and federally-mandated THC tests. CBG products have been slowly entering the hemp product market for the past several years, and we will likely see a steady increase in CBG products available to consumers as time presses on.

How Does CBG Work?

Most of the CBG research that has been performed to date has focused on understanding how this cannabinoid interacts with different types of chemical receptors in the body. This has established a foundation of knowledge which clinical researchers can use to investigate the therapeutic efficacy of CBG against different health conditions.

When it comes to CB1 and CB2 receptors, CBG has been shown to act as either a partial agonist or antagonist, meaning it can either stimulate (agonize) or block (antagonize) the receptors depending on the pre-existing activity of the receptor before CBG arrived. This might make CBG what is called a protean agonist, a compound that does different things at a receptor depending on whether that receptor is already stimulated or blocked.

CBG stimulates and desensitizes vanilloid receptors including TRPV1, 2, 3, and 4. These receptors are located throughout the central nervous system and peripheral nervous system and are associated with various sensations in the body like temperature and pressure. They are often expressed on neurons involved with detecting pain and are sometimes the targets of pain killing drugs. (Levine, & Alessandri-Haber 2007) These receptors are often referred to as capsaicin receptors, because the capsaicin in hot peppers acting at these receptors is what is responsible for the sensation of spiciness. TRPV receptors are also implicated in Cannabinoid Hyperemesis Syndrome, and many patients suffering from CHS find relief from capsaicin cream and patches on the stomach.

A similar receptor that is responsible for cold sensations, rather than hot sensations, is TRPM8, which CBG antagonizes. CBG can also antagonize 5HT1A and GPR55 receptors, among others. GPR55 is found throughout the brain and in other areas like fatty tissues and bone cells – indicating that activity at the GPR55 receptor may have effects on things like motor coordination, obesity and bone growth or deterioration. (Lipina, Walsh, Mitchell, Speakman, Wainwright, & Hundal) (Shore, & Reggio, 2015)

There are several other chemical receptors that CBG interacts with. Rather than stimulating, CBG can exhibit antagonistic activity at 5HT1A (Serotonin), TRPM8, and GPR55 receptors. CBG also stimulates adrenoceptors, which are the primary receptors that adrenaline and norepinephrine interact with. (Deiana, 2017)

CBG also interacts with all sorts of enzymes, ultimately inhibiting several pro-inflammatory enzymes like COX-1 and COX-2. CBG also inhibits enzymes responsible for the breakdown of certain endocannabinoids like 2-AG. Additionally, cannabigerol can inhibit the uptake of critical neurotransmitters like dopamine, serotonin, norepinephrine and GABA. (Deiana, 2017)
In case all of this talk of chemical receptors has become confusing, just know this: the activity of CBG in the body is extremely diverse! It is also very important to note that few studies have been done in humans that examine how CBG moves through the body and is processed by the body, so there’s a lot we don’t know quite yet. Our understanding of CBG’s activity at different receptors can at least help clinicians understand the systems of the body that CBG may affect and focus their attention on potential therapeutic applications and risk factors.

From the Collection of The Lloyd Library and Museum

Is CBG Safe?

Compared to more well-studied cannabinoids like THC and CBD, there have not been a lot of safety studies performed on CBG. Humans have been exposed to CBG in trace concentrations for many years, and cannabigerol is one of the minor components of the pharmaceutical Cannabis extract product, Sativex, but it is only relatively recently that we have been exposed to products containing CBG in significant concentrations and in forms readily available to the public.

In one study examining CBG’s effects on appetite in rodents, the rodents were given up to 240mg/kg of CBG and no adverse effects were detected. (Brierley, Samuels, Duncan, Whalley, & Williams, 2016) The LD50, or median lethal dose, for cannabigerol is not well understood. We know that CBD can potentially interact with liver enzymes to slow the body’s metabolism of certain drugs, which can be quite dangerous in certain situations. CBG’s effects on liver enzymes are not well understood, so we don’t have a clear picture of how CBG may interact with medications, and at what dosages.
Because the safety profile of CBG is not well understood, it is important to be cautious, especially when taking it with medications.

Therapeutic Potential of CBG

Cannabigerol has been suggested as a potential treatment for all sorts of medical conditions – however it is important to note that these suggestions are mostly based on preliminary research that has not been performed clinically in humans. Some of the conditions that researchers have indicated that CBG may be affect positively are mood disorders, feeding disorders, inflammation, cancer, glaucoma, inflammatory bowel disease, bacterial infections, psoriasis, bone disorders, neuroinflammation, and hormonal imbalances. (Deiana, 2017) It is also speculated that CBG may be effective in treating pain, as it is pharmacologically active at many receptors that are traditionally associated with pain and pain relief.

How Does CBG Affect CBD?

So, let’s say you were to mix CBD and CBG. What would happen? Little is known about how CBG and CBD interact with one another, but there are a couple of published studies that provide a bit of insight. One study examined how CBG affects the anti-nausea effects of CBD in rodents. The study revealed that CBG can actually reverse, or undo, the anti-nausea effects of CBD if administered before CBD. (Rock, Goodwin, Limebeer, Breuer, Pertwee, Mechoulam, & Parker, 2011) However, CBD and CBG in combination may be more effective at treating inflammation than either one alone. (Mammana, Cavalli, Gugliandolo, Silvestro, Pollastro, Bramanti, & Mazzon 2019)

Conclusions

Ultimately CBG, like all of the cannabinoids, are fascinating compounds that exhibit myriad effects on our bodies. However, we still don’t understand a lot of these effects, and there are few, if any, human clinical studies that have been performed on CBG. Based on the pharmacological activity of CBG, there are all sorts of potential clinical applications that should be explored such as appetite stimulation, mood regulation, infections, glaucoma, pain and more. CBG does interact with CBD in unique ways, possibly undoing CBD’s anti-nausea effects, while potentially enhancing each other’s anti-inflammatory activity. Ultimately consumers should be optimistically cautious about CBG’s safety profile and should keep good experience journals to share with their health care professional if using CBG-rich hemp extract products for the treatment of a medical condition.

Jason is a science educator and natural products researcher living in Southern Oregon. He is the author of Curious About Cannabis: A Scientific Introduction to a Controversial Plant and is the host of the Curious About Cannabis Podcast. Curious About Cannabis is a learning initiative by Natural Learning Enterprises, a mission-driven company dedicated to enhancing critical thinking skills and scientific literacy about the natural world.

References

  1. Deiana S. (2017) Potential Medical Uses of Cannabigerol: A Brief Overview. Handbook of Cannabis and Related Pathologies. 958-967.

  2. Mechoulam R, Gaoni Y. Hashish. IV. (1965) The isolation and structure of cannabinolic cannabidiolic and cannabigerolic acids. Tetrahedron. 21(5):1223-1229. doi:10.1016/0040-4020(65)80064-3

  3. Levine JD, Alessandri-Haber N. (2007) TRP channels: targets for the relief of pain. Biochimica et Biophysica Acta – Molecular Basis of Disease. Elsevier. 1772(8): 989.

  4. Lipina C, Walsh SK, Mitchell SE, Speakman JR, Wainwright CL, Hundal HS. GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues. The FASEB Journal. 33(1).

  5. Shore DM, Reggio PH. (2015) The therapeutic potential of orphan GPCRs, GPR35 and GPR55. Front. Pharmacol. 6:69.

  6. Deiana S. (2017) Potential Medical Uses of Cannabigerol: A Brief Overview. Handbook of Cannabis and Related Pathologies. 958-967.

  7. Deiana S. (2017) Potential Medical Uses of Cannabigerol: A Brief Overview. Handbook of Cannabis and Related Pathologies. 958-967.

  8. Brierley DI, Samuels J, Duncan M, Whalley BJ, Williams CM. (2016) Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats. Psychopharmacology. 2016. 233: 3603-3613.

  9. Deiana S. (2017) Potential Medical Uses of Cannabigerol: A Brief Overview. Handbook of Cannabis and Related Pathologies. 958-967.

  10. Rock EM, Goodwin JM, Limebeer CL, Breuer A, Pertwee RG, Mechoulam R, Parker LA. (2011) Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews. Psychopharmacology. 215: 505-512.

  11. Mammana S, Cavalli E, Gugliandolo A, Silvestro S, Pollastro F, Bramanti P, Mazzon E. (2019) Could the combination of two non-psychotropic cannabinoids counteract neuroinflammation? Effectiveness of cannabidiol associated with cannabigerol. Medicina (Kaunas). 55(11): 747.