Studies indicate that CBG may have therapeutic potential in treating neurologic disorders (e.g., Huntington disease, Parkinson disease, and multiple sclerosis) and inflammatory bowel disease, as well as having antibacterial activity. This review focuses on the unique pharmacology of CBG, our current knowledge of its possible therapeutic utility, and much more.
Cannabinoid synthesis begins with the precursor molecules olivetolic acid and geranyl-pyrophosphate, which combine to form cannabigerolic acid (CBGA). CBGA serves as the precursor to most other cannabinoids and is converted to D9-tetrahydrocannabinolic acid (D9-THCA), cannabidiolic acid (CBDA), and cannabichromenic acid.
Because CBGA serves as the precursory molecule to the other cannabinoids, it is normally found in very low quantities in Cannabis; however, strains with reduced activity of the three major synthesis enzymes can accumulate higher levels of CBGA. All enzymatically produced cannabinoids (including CBG) are produced as their acidic form and are then decarboxylated by heat to create the “active” form.
Potential Therapeutic Potentials for CBG
Based on the receptor signaling of the a-2, 5-HT1A, and PPARg receptors and the reported affinities of CBG at these receptors (in the tens of nanomolars to sub-nanomolar range), there are many reasons to believe that CBG will have therapeutic potential.
Neuroprotection and Neuromodulation
A number of studies have shown that CBG and a second-generation synthetic quinone derivative, VCE-003.2, have neuroprotective potential in vitro and in animal models to reduce the severity of neurologic illnesses, such as Huntington disease (HD), amyotrophic lateral sclerosis, Parkinson disease, and multiple sclerosis.
Cannabigerol has been explored as a therapeutic for gastrointestinal diseases such as colorectal cancer and colitis using mouse models. Although the authors conclude that this reduction was mediated by TRPM8, these studies were performed in cell culture rather than in the murine model. Orally administered CBG reduced colonic inflammation as measured by significantly reducing myeloperoxidase (MPO) activity, IL-1b levels, and serum fluorescein isothiocyanate (FITC)-dextran concentration. In contrast, CBD on its own did not induce significant changes to these metrics. CBG has also been shown to increase feeding in rats and to reduce weight loss associated with cisplatin chemotherapy. However, an earlier study found no impact of CBG on feeding behavior. Unlike D9-THC and CBD, CBG has not been found to have antiemetic effects and appears to oppose the antiemetic effects of CBD.
Taken together, these studies indicate that there may be a role for cannabigerol in chemotherapy-associated weight loss and loss of appetite.
Metabolic syndrome affects millions of Americans and contributes to the highest burden of healthcare costs and preventable mortality in the country. A clinical diagnosis, metabolic syndrome is a combination of insulin resistance, obesity, hypertension, high levels of lowdensity lipoprotein, and reduced levels of high-density lipoprotein. Although a wide array of medications and surgical interventions are available for metabolic syndrome, few treatments are effective enough to serve as monotherapy, and many patients need multiple medications with harsh side effects to keep this chronic illness at bay.
Recent studies on CBG provide promise for its use as part of a multifactorial pharmacotherapy for metabolic syndrome and its components. Hypertension, one component of metabolic syndrome, can be modestly reduced with a-2 agonist therapy, which reduces synaptic norepinephrine levels to reduce vasoconstriction and improve blood pressure. CBG is currently the only known cannabinoid that is an agonist at the adrenergic receptor. In addition, as previously mentioned, CBG and its derivatives are shown to act on PPARg receptors in its role on neuroinflammation.
A number of cannabinoids have been reported to have antibacterial activity; however, CBG was found to be among the most potent cannabinoids tested against antibiotic resistant strains of Staphylococcus aureus.
Research into cannabigerol is in its infancy but has shown promise for addressing a diverse array of therapeutic needs. Based on its pharmacodynamics, here we highlight potential indications for CBG and its derivatives to improve available drug treatment regimens for selected diseases and medical conditions.
First, there is potential for CBG as a major player in the treatment of metabolic disease as described by its action on the PPAR family of receptors to improve insulin sensitivity and adipogenesis.
Second, several studies have described the neuroprotective effects of CBG through action on the PPAR family of receptors. CBG may play a role for improving quality of life in these vulnerable populations, as the few drugs currently available for neurodegenerative diseases also carry uncomfortable and disabling side effects.
Third, similar to other phytocannabinoid derivatives, CBG may play an important role for improving the drug cocktails of patients who struggle with disorders of executive function, such as schizophrenia and ADHD. Researchers have studied the effects of CBG as a safe appetite stimulant in chemotherapy-related appetite suppression in vivo and as an agent that reduces in vitro signs of pathology in colitis and colorectal cancer.
In closing, although there is much to suggest that CBG may provide alternative therapeutics for a number of disorders, much is left to learn.
(Journal of Pharmacology and Experimental Therapeutics February 2021)