Spring 2020

Cannabigerol Is Moving Center Stage

A lesser-known cannabinoid shows promise for a range of conditions.

Cannabis has been described as a “medical treasure trove” because of the possibilities it holds for the treatment of a number of different medical conditions.1 To date, most of the clinical research of cannabis has focused on THC and CBD; however, cannabigerol (CBG)—a lesser-known cannabinoid—is gaining significant interest within the scientific community with evidence that it may be useful for a wide range of medical conditions including neurological disorders, autoimmune diseases, pain, glaucoma, and cancer, among others.

Mother Cannabinoid
CBG has been referred to as the mother of all cannabinoids or the stem cell of cannabinoids, as it’s the primary biosynthetic precursor of other cannabinoids.2 Early in the cannabis flowering cycle, cannabigerolic acid (CBGA) is converted by enzymes to cannabinoids including THC, CBD, CBG, cannabinol (CBN), and cannabichromene (CBC). Because CBGA is quickly converted to THC or CBD as the plant matures, only small amounts of CBG are found in the Cannabis sativa plant.3 The low concentration of CBG in the plant has made studying the compound challenging. However, in hemp and species with low THC concentration, the concentration of CBG can be much higher. Furthermore, genetic modification has resulted in some strains being developed that are almost all CBG and CBGA.

CBG is a relatively weak partial agonist of the cannabinoid receptors CB1 and CB2, with its effects at CB2 thought to play a role in inhibiting the intoxicating effects of THC.2 CBG also increases the body’s endogenous anandamide, which is involved in pain, depression, appetite, memory, and fertility.4

CBG has been found to interact with a number of receptors implicated in pain, inflammation, and heat sensitization including transient receptor potential (TRP) channels. CBG stimulates TRPV1, TRPV2, TRPV3, TRPV4, and TRPA1 receptors and antagonizes TRPM8 receptors.5 Additionally, CBG is a potent alpha-2-adrenoceptor agonist that may be involved in pain and also help reduce stress, decrease anger, lower blood pressure, and improve working memory and executive function.6 It shows effects as a moderately potent 5-HT1A receptor antagonist, which could help control mood and may make CBG a candidate as a treatment for depression.3,6 CBG may also inhibit gamma aminobutyric acid uptake, which may be beneficial for muscle relaxation and antianxiety effects.3

Clinical Evidence
It’s important to recognize that the clinical evidence for CBG is limited primarily to tissue studies and preclinical animal studies, which require validation in humans. Regardless, these studies demonstrate that CBG and synthetic CBG derivatives have tremendous potential as candidates for potential pharmacological treatment options in a number of different of health conditions.

Neurodegenerative Diseases
CBG and CBG derivatives are noted to provide significant anti-inflammatory and neuroprotective benefits that could lead to their development as novel treatment options in a number of different neurodegenerative diseases.

Huntington’s Disease (HD)
In one study, researchers evaluated the effects of CBG in two different mice models of HD. In the first, mice were intoxicated with 3-nitropropionate, a known neurotoxin that causes reactive microgliosis and upregulation of proinflammatory substances. In these mice, CBG provided significant neuroprotective effects, with improvements in motor deficits and preservation of striatal neurons. In addition, CBG attenuated reactive microgliosis and proinflammatory factors while improving antioxidant defenses. In a second model, CBG was used to treat R6/2 mice with deteriorated rotarod performance. In these mice, CBG partially normalized the expression of a series of altered genes linked to HD, most notably the huntingtin protein. Furthermore, there was modest improvement in the gene expression for brain-derived neurotrophic factor, insulinlike growth factor-1, and peroxisome proliferator-activated receptor gamma (PPARgamma). There was also a small but significant reduction in the aggregation of mutant huntingtin in the striatal parenchyma in the CBG-treated animals.7

Synthetic derivatives of CBG have also been developed and studied. VCE-003 is a synthetic quinolone CBG derivative that’s been described as a novel neuroprotective and anti-inflammatory cannabinoid. VCE-003 activates PPARgamma receptors, which are involved in neuroinflammatory responses.8 A second-generation quinolone CBG derivative identified as VCE-003.2 also activates PPARgamma receptors and appears to exert a prosurvival action in progenitor cells during neuronal differentiation. Moreover, VCE-003.2 has also been shown to attenuate cell death and reduce mutant huntingtin aggregates in striatal cells, reduce proinflammatory markers, and improve antioxidant defenses in the brain.9,10

An oral drug candidate, EHP-102 (active ingredient being VCE-003.2) has also been evaluated in two different mice models of HD and was shown to prevent neuroinflammation and neurodegeneration. In the first model, mice were modified to express the huntingtin protein. These mice were subsequently given EHP-102, which was found to prevent neurodegeneration, neuroinflammation, and impaired motor function. In the second model, mice were given 3-nitropropionate to induce HD-like symptoms. The data from these models suggest that the oral formulation of EHP-102 could achieve disease modification rather than only symptomatic relief for HD.7,9

Parkinson’s Disease (PD)
VCE-003.2 has also been investigated as a potential treatment option for PD using lipopolysaccharide-lesioned mice, which represents an experimental model of PD. VCE-003.2 was shown to be neuroprotective against inflammation-driven neuronal damage.11

Multiple Sclerosis (MS)
A study published in the Journal of Neuroimmune Pharmacology in 2012 looked at CBG and its effect on MS. Researchers found that CBG was a potent anti-inflammatory agent and neuroprotectant that not only helped mediate the symptoms of MS but also modulated the expression of key genes involved in the disease.8

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s Disease
The neuroprotective effects of VCE-003.2 have also been evaluated in an experimental model of ALS using SOD1G93A transgenic mice. These mutant mice were treated with VCE-003.2 from 60 days up to 18 weeks (advanced stage in disease progression) when they were euthanatized and used for analysis of neuropathological progression. VCE-003.2 provided antioxidant protection and inhibited neuronal damage. VCE-003.2 was found to attenuate most of the progressive symptoms seen in ALS, including progressive weight loss, neurological deterioration associated with a marked loss of spinal cholinergic motor neurons, glial reactivity, and elevations in several biochemical markers (cytokines, glutamate transporters) that indirectly reflect the glial proliferation and activation in the spinal cord. The researchers note that such benefits would need to be validated in other ALS models prior to being translated to the clinical level.12

Future treatments for ALS and other disorders also may entail combining several different cannabinoids. An in vitro study showed enhanced benefits (antioxidant, anti-inflammatory, and antiapoptotic effects) when using both CBG and CBD together, suggesting that further evaluation of CBG-CBD combination in vivo preclinical models of ALS is warranted.13

Endocannabinoid receptors are found throughout the eye and are involved in the regulation of retinal neurotransmission, neuroplasticity, and neuroprotection. These receptors are also responsible for the formation and outflow of aqueous humor. A number of different cannabinoids have been shown to be able to decrease intraocular pressure associated with glaucoma. A 1990 study using CBG in cats with glaucoma concluded that both THC and CBG modestly reduce intraocular pressure and increase aqueous outflow through the intricate drainage channels in the tissue surrounding the eye. Following chronic administration of CBG unilaterally to the cornea via Alzet osmotic minipumps (small, implantable pumps for research in laboratory animals) and the connection of extraocular cannulas, a considerable fall in ocular tension amounting to 4 to 7 mm Hg occurred. Both CBG and THC produced a two- to three-fold increase in aqueous outflow facility. These results suggest that CBG and related cannabinoids may have therapeutic potential for the treatment of glaucoma.14

Autoimmune Disorders
CBG’s anti-inflammatory and modulating effects on the immune system response makes CBG a potential treatment option for a number of autoimmune disorders including inflammatory bowel disease (IBD) and psoriasis.

Anecdotal evidence shows that CBG may be of benefit in the treatment of IBDs such as Crohn’s disease and ulcerative colitis. In these conditions, chronic inflammation and irritation of the intestinal lining occur as a result of an exaggerated immune response that results in excessive nitric oxide and oxidative stress. In an animal study using mice, CBG was found to reduce the inflammation associated with colitis. CBG’s effects on CB2 receptors is believed to reduce nitric oxide production in macrophages and reactive oxygen species formation in intestinal epithelial cells.15

Psoriasis may occur due to a disruption of the endocannabinoid system, which in turn causes a defective autoimmune response. The dry flakes of silvery-white skin scales characteristic of psoriasis result from the excessively rapid proliferation of skin cells that is triggered by inflammatory chemicals produced by specialized white blood cells called T-cells. CBG, along with several other cannabinoids including THC, CBD, and CBN, appears to effectively inhibit overactive T-cells, which supports their role in the treatment of psoriasis.16

Topical preparations derived from cannabis have long been used as antibacterial agents. A 2008 study found that THC, CBD, CBG, CBC, and CBN displayed activity against methicillin-resistant Staphylococcus aureus (MRSA) strains.17

In another study, microbiologists compared the MRSA-killing activity of THC, CBD, and CBG. CBG was found to be the most potent and killed not only the MRSA microbes but also the remaining “biofilm” that often forms on patients’ skin and medical implants. The scientists also noted that CBG’s effects were on par with the antibiotic vancomycin. The lead investigator also noted that while cannabinoids are “clearly great druglike compounds, far more research is necessary before the results can be tested on human patients or applied in medical settings.”18

Bladder Conditions
CBG may also be a future treatment option for preventing bladder dysfunction disorders. The upregulation of TRPM8 in nerve fibers has been implicated in overactive and painful bladder syndromes. CBG is a relatively potent TRPM8 antagonist and helps inhibit bladder contractions similarly to THC and greater than that of CBD.19

The appetite-stimulating properties of cannabis are well documented, with these effects commonly reported as an effect of THC. In rats, however, CBG has also been shown to elicit hyperphagia by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects associated with THC. Researchers have suggested that these data provide a rationale for preclinical investigation of CBG as a novel treatment in models of cancer- or chemotherapy-induced cachexia, for which there is an urgent unmet clinical need for well-tolerated appetite stimulants.20

Cancer Research
CBG has been shown to act on a number of different receptors that contribute to cancer cell growth, with research noted in colorectal, breast, prostate, and ovarian cancers.

Breast Cancer
In basic research models, CBG in high doses has proven to be an effective cytotoxic on human epithelioid carcinoma and is one of the more effective phytocannabinoids against breast cancer.21

Ovarian Cancer
Evidence that CBG may be considered as a possible future treatment of ovarian cancer comes from an in vitro tissue-based study of the effects of CBD and CBG on ovarian cancer cells. Preliminary data suggested that the cytotoxicity of CBD and CBG is dependent, in part at least, on the cannabinoid at the G protein-coupled receptor 55, which some consider the third major cannabinoid receptor, CB3.22

Cisplatin is a chemotherapeutic agent widely used in the treatment of ovarian cancer. Unfortunately, with extended use, cisplatin resistance is a significant and common problem. Of interest is that CBD and CBG appear to have distinct mechanisms of activity against cisplatin-sensitive and cisplatin-resistant cells. As such, CBD and CBG could be developed as new treatments for ovarian cancer used alone or as add-on treatment with cisplatin to help overcome cisplatin resistance.

Prostate Cancer
Activation of TRPM8 channels has been to shown to have a proliferative effect, increasing tumor growth in prostate cancer. CBG’s antagonistic effects on TRPM8 may be beneficial in the treatment of prostate cancer.23

Colon Cancer
CBG’s effects in blocking TRPM8 channels has been shown to have proapoptotic effects in cancer cells as well to be chemopreventive and curative in experimental in vivo models of colon cancer.5

Moderate doses of CBG produced behaviors that were consistent to those produced by the tricyclic antidepressant imipramine in the tail suspension test. Due to CBG’s good safety profile, it could offer beneficial effects over that of imipramine and other tricyclic antidepressants, which are known to cause many side effects.24

As these studies show, CBG appears to offer promise for a number of conditions for which there’s a definite need for novel treatment options. As support continues to mount for the legalization of medical cannabis as well as easier access to hemp as part of the 2018 Farm Bill, it’s likely that there will be larger human clinical trials for CBG in the near future.

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.


1. Leichman AK. The Israeli pharmacologist who kick-started marijuana research. ISRAEL21c. May 14, 2012.

2. Gauson LA, Stevenson LA, Thomas A, Baillie GL, Ross RA, Pertwee RG. Cannabigerol behaves as a partial agonist at both CB1 and CB2 receptors. Paper presented at: International Cannabinoid Research Society 17th Annual Symposium on the Cannabinoids; June 26–30, 2007; Saint-Sauveur, Quebec, Canada.

3. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.

4. Manzanares J, Julian MD, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4(3):239-257.

5. Borrelli F, Pagano E, Romano B, et al. Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a cannabis-derived non-psychotropic cannabinoid. Carcinogenesis. 2014;35(12):2787-2797.

6. Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG. Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol. 2010;159(1):129-141.

7. Valdeolivas S, Navarrete C, Cantarero I, Bellido ML, Muñoz E, Sagredo O. Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics. 2015;12(1):185-199.

8. Granja AG, Carrillo-Salinas F, Pagani A, et al. A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis. J Neuroimmune Pharmacol. 2012;7(4):1002-1016.

9. Díaz-Alonso J, Paraíso-Luna J, Navarrete C, et al. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease. Sci Rep. 2016;6:29789.

10. Aguareles J, Paraíso-Luna J, Palomares B, et al. Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration. Transl Neurodegener. 2019;8:9.

11. García C, Gómez-Cañas M, Burgaz S, et al. Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson’s disease: possible involvement of different binding sites at the PPARγ receptor. J Neuroinflammation. 2018;15(1):19.

12. Rodríguez-Cueto C, Santos-García I, García-Toscano L, et al. Neuroprotective effects of the cannabigerol quinone derivative VCE-003.2 in SOD1G93A transgenic mice, an experimental model of amyotrophic lateral sclerosis. Biochem Pharmacol. 2018;157:217-226.

13. Mammana S, Cavalli E, Gugliandolo A, et al. Could the combination of two non-psychotropic cannabinoids counteract neuroinflammation? Effectiveness of cannabidiol associated with cannabigerol. Medicina (Kaunas). 2019;55(11):E747.

14. Colasanti BK. A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol. J Ocul Pharmacol. 1990;6(4):259-269.

15. Borrelli F, Fasolino I, Romano B, et al. Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochem Pharmacol. 2013;85(9):1306-1316.

16. Norooznezhad AH, Norooznezhad F. Cannabinoids: possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation. Med Hypotheses. 2017;99:15-18.

17. Appendino G, Gibbons S, Giana A, et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 2008;71(8):1427-1430.

18. Farha MA, El-Halfawy OM, Gale RT, et al. Uncovering the hidden antibiotic potential of cannabis. ACS Infect Dis. 2020;6(3):338-346.

19. Pagano E, Montanaro V, Di Girolamo A, et al. Effect of non-psychotropic plant-derived cannabinoids on bladder contractility: focus on cannabigerol. Nat Prod Commun. 2015;10(6):1009-1012.

20. Brierley DI, Samuels J, Duncan M, Whalley BJ, Williams CM. Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats. Psychopharmacology (Berl). 2016;233(19-20):3603-3613.

21. Russo EB, Marcu J. Cannabis pharmacology: the usual suspects and a few promising leads. Adv Pharmacol. 2017;80:67-134.

22. Sooda KKY. Evaluation of the effects of cannabinoids CBD and CBG on human ovarian cancer cells in vitro [doctoral thesis]. Huddersfield, England: University of Huddersfield; 2019.

23. Grolez GP, Gkika D. TRPM8 puts the chill on prostate cancer. Pharmaceuticals (Basal). 2016;9(3):E44.

24. Pharmaceutical compositions comprising cannabigerol. Google Patents website.


CRx Podcast Debuts on Pharmacy Podcast Network

By Great Valley Publishing Company

How the Coronavirus Pandemic Will Affect the Cannabis Industry


By Kris Krane

Cannabis Use for Treating Disease


By Janice Newell Bissex, MS, RDN

Medical and Recreational Marijuana Use


By Liz Marr, MS, RDN, FAND

Medical Cannabis — Continuing Controversy


By Mark D. Coggins, PharmD, BCGP, FASCP