Accurate Education – Marijuana (Cannabis): CBG (Cannabigerol)

CBG has attracted less attention than Δ-9 THC and CBD, but nowadays is gaining interest among the medical community. Some commercial hemp varieties have CBG and CBGA as their main cannabinoids and, therefore, CBG is developing its place in the therapeutic cannabis market.

Therapeutic Benefits of CBG

Research on CBG is very limited, consisting mostly of preclinical studies in the lab and with animals but few human studies. Early research suggests that CBG may be able to improve the following health conditions:

Anxiety

Preclinical evidence suggests the phytocannabinoid cannabigerol (CBG) could be useful in treating brain disorders, including stress and anxiety-related disorders. CBG is purported to reduce anxiety and symptoms of obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and depression. In a 2021 study in in a mouse model of post-traumatic stress disorder (PTSD), researchers explored whether CBG disrupts various contextually conditioned fear memory processes and trauma-induced anxiety-related behavior.

Appetite Stimulation

A 2016 study on rats suggested that CBG could stimulate the appetite. CBG has also been shown to increase feeding in rats and to reduce weight loss associated with chemotherapy. Unlike Δ-9 THC and CBD, CBG has not been found to have anti-nausea effects and appears to oppose the anti-nausea effectsof CBD. Taken together, these studies suggest that there may be a role for CBG in chemotherapy-associated weight loss and loss of appetite.

Inflammatory Bowel Disease (IBD)

CBG may reduce the inflammation associated with inflammatory bowel disease, based on a 2013 study conducted on mice. In a 2020 study using a mouse model, orally administered CBG reduced colonic inflammation and adding fish oil enhanced the effect.

Bladder Dysfunction

A 2015 study evaluated how five different cannabinoids affect the bladder, concluding that CBG offers the most promise at treating bladder dysfunctions.

Neurodegenerative Disorders

CBG has previously been reported to have disease-modifying anti-inflammatory effects in mouse models of Huntington’s disease, multiple sclerosis, Parkinson’s disease, and amyotrophic lateral sclerosis. These effects are likely mediated by PPARγ, and not cannabinoid receptors. CBG might have neuroprotective properties, according to a 2015 study that looked at mice with the neurodegenerative condition, Huntington’s disease. The study concluded that CBG might show promise in treating other neurodegenerative conditions.

Neuroinflammation and Oxidative Stress

In laboratory studies CBG pre-treatment reduces inflammation, as by reducing inflammatory agents including IL-1β, TNF-α, IFN-γ and PPARγ protein levels. but also oxidative stress by reducing nitrotyrosine, SOD1 and iNOS protein levels and restoring Nrf-2 levels. Together, these findings suggest neuroprotective benefits of CBG that may offer potential treatment against neuroinflammation and oxidative stress.

Cancer

A 2014 study evaluated colon cancer in rats, concluding that CBG might reduce the growth of cancer cells and other tumors.

Dosing of CBG

Very little is known about optimal dosing of CBG. In the US Pacific Northwest, CBG-predominant cannabis flower and extract have begun to increase in popularity among cannabis users. A 2021 study investigated the reasons for use and self-reported therapeutic effects of 127 cannabis users of CBG-predominant strains (containing >50% CBG). To establish context, none of the marijuana flower strains available at the LA dispensary pharmacies or the hemp flowers available at the CBD stores appear to have more than 2% CBG.

Neurobiology of CBG

CBG research has suggested multiple mechanisms by which it may offer therapeutic benefits, but knowledge of CBG is in its infancy with little definitive clinical human research. Thus, much of what is “known” is very speculative.

The proposed mechanisms of CBG activity do not likely involve significant contribution from cannabinoid receptors CB1 or CB2, but possibly include GPR55 and/or modulation of PPARγ. CBG has also been shown to have in vitro activity at the α2 adrenoceptor,  5HT1A,  and several transient receptor potential (TRP) channels.

Cannabinoid Receptors

In a 2020 study, CBG was found to be a weak partial agonist of both CB1 receptor (CB1R) and CB2 receptor (CB2R). Previous reports have similarly described CBG as a weak partial agonist of these two receptors, with low affinity for both. In vivo, CBG produced a small analgesic effect and an anxiolytic effect. The authors concluded however, it was possible their in vivo analgesic and anxiolytic effects may have occurred via cannabinoid receptor-independent mechanisms.

CBG has previously been reported to have disease-modifying anti-inflammatory effects in mouse models of Huntington’s disease, multiple sclerosis, Parkinson’s disease, and amyotrophic lateral sclerosis. These effects are likely mediated by PPARγ, and not cannabinoid receptors.

α2-Adrenoceptor Agonist

CBG is a highly potent agonist for α2-adrenoceptor which has significant implications for potential therapeutic uses and adverse side effects. The catecholamines neurotransmitters (dopamine, norepinephrine, and epinephrine) use different receptors to exert different physiologic effects. The main receptor families that mediate these effects are the adrenergic receptors [alpha (a-1 and a-2) and beta (b-1, b-2, and b-3) families] and the dopamine receptors (D1 through D5 receptors).

Serotonin 5-HT1A receptor Blocker

CBG acts as a blocker of the serotonin 5-HT1A receptor, which can result in decreased anxiety and muscle tension.

When associated with CBD, it has anti-inflammatory activity by reducing tumor necrosis factor (TNF) expression and upregulating Interleukin–10 (IL-10) and Interleukin–37 (IL-37) levels.

CBG also shows activity on TRP channels and CB1 receptors, as well as inhibiting AEA reuptake, suggesting possible benefits for pain 

Additionally, CBG has shown anti-tumor activity in the colon by inhibiting transient receptor potential melastatin 8 (TRPM8) channels.