Cannabigerol

J Neuroimmune Pharmacol. 2012 Dec;7(4):1002-16.

A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis.[Pubmed: 22971837]

Phytocannabinoids like ∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation.
METHODS AND RESULTS:
As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of Cannabigerol (CBG) on CB(1), CB(2) and PPARγ binding affinities, identifying Cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity, activated PPARγ transcriptional activity and inhibited the release of pro-inflammatory mediators in LPS-stimulated microglial cells. Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to investigate the anti-inflammatory activity of this compound in vivo. Motor function performance was evaluated and the neuroinflammatory response and gene expression pattern in brain and spinal cord were studied by immunostaining and qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV infection, decreased microglia reactivity and modulated the expression of genes involved in MS pathophysiology.
CONCLUSIONS:
These data lead us to consider VCE-003 to have high potential for drug development against MS and perhaps other neuroinflammatory diseases.

Biochem Pharmacol. 2013 May 1;85(9):1306-16.

Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.[Pubmed: 23415610]

Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialized countries. Anecdotal and scientific evidence suggests that Cannabis use may have a positive impact in IBD patients.
METHODS AND RESULTS:
Here, we investigated the effect of Cannabigerol (CBG), a non-psychotropic Cannabis-derived cannabinoid, in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulphonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters (colon weight/colon length ratio and myeloperoxidase activity), by histological analysis and immunohistochemistry; interleukin-1β, interleukin-10 and interferon-γ levels by ELISA, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by western blot and RT-PCR; CuZn-superoxide dismutase (SOD) activity by a colorimetric assay. Murine macrophages and intestinal epithelial cells were used to evaluate the effect of CBG on nitric oxide production and oxidative stress, respectively. CBG reduced colon weight/colon length ratio, myeloperoxidase activity, and iNOS expression, increased SOD activity and normalized interleukin-1β, interleukin-10 and interferon-γ changes associated to DNBS administration. In macrophages, CBG reduced nitric oxide production and iNOS protein (but not mRNA) expression. Rimonabant (a CB1 receptor antagonist) did not change the effect of CBG on nitric oxide production, while SR144528 (a CB2 receptor antagonist) further increased the inhibitory effect of CBG on nitric oxide production.
CONCLUSIONS:
In conclusion, CBG attenuated murine colitis, reduced nitric oxide production in macrophages (effect being modulated by the CB2 receptor) and reduced ROS formation in intestinal epithelial cells. CBG could be considered for clinical experimentation in IBD patients.

Neurotherapeutics. 2015 Jan;12(1):185-99.

Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.[Pubmed: 25252936]

METHODS AND RESULTS:
Herein, we studied the effects of Cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. Cannabigerol was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, Cannabigerol attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of Cannabigerol in R6/2 mice. whose expression was altered in R6/2 mice but partially normalized by Cannabigerol treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in Cannabigerol-treated animals.
CONCLUSIONS:
In conclusion, our results open new research avenues for the use of Cannabigerol, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

Arch Pharm Res. 1998 Jun;21(3):353-6.

Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells.[Pubmed: 9875457]

METHODS AND RESULTS:
Geraniol (1), olivetol (2), cannabinoids (3 and 4) and 5-fluorouracil (5) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) and NIH 3T3 fibroblasts using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay.
CONCLUSIONS:
Cannabigerol (3) exhibited the highest growth-inhibitory activity against the cancer cell lines.

Carcinogenesis. 2014 Dec;35(12):2787-97.

Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid.[Pubmed: 25269802]

Cannabigerol (CBG) is a safe non-psychotropic Cannabis-derived cannabinoid (CB), which interacts with specific targets involved in carcinogenesis. Specifically, Cannabigerol potently blocks transient receptor potential (TRP) M8 (TRPM8), activates TRPA1, TRPV1 and TRPV2 channels, blocks 5-hydroxytryptamine receptor 1A (5-HT1A) receptors and inhibits the reuptake of endocannabinoids.
METHODS AND RESULTS:
Here, we investigated whether Cannabigerol protects against colon tumourigenesis. The in vivo antineoplastic effect of Cannabigerol was assessed using mouse models of colon cancer. CRC cells expressed TRPM8, CB1, CB2, 5-HT1A receptors, TRPA1, TRPV1 and TRPV2 mRNA. CBG promoted apoptosis, stimulated ROS production, upregulated CHOP mRNA and reduced cell growth in CRC cells. Cannabigerol effect on cell growth was independent from TRPA1, TRPV1 and TRPV2 channels activation, was further increased by a CB2 receptor antagonist, and mimicked by other TRPM8 channel blockers but not by a 5-HT1A antagonist. Furthermore, the effect of Cannabigerol on cell growth and on CHOP mRNA expression was reduced in TRPM8 silenced cells. In vivo, Cannabigerol inhibited the growth of xenograft tumours as well as chemically induced colon carcinogenesis.
CONCLUSIONS:
Cannabigerol hampers colon cancer progression in vivo and selectively inhibits the growth of CRC cells, an effect shared by other TRPM8 antagonists. Cannabigerol should be considered translationally in CRC prevention and cure.

J. Pharm. Sci.,1982 Dec;71(12):1319-23.

Synthesis and Antimicrobial Activities of Certain Cannabichromene and Cannabigerol Related Compounds[Pubmed: 7153877]

METHODS AND RESULTS:
Cannabichromene homologs, analogs, and isomers as well as the C1-homolog and isomer of Cannabigerol were prepared and tested for their antimicrobial and antifungal properties. Spectral data of all compounds synthesized are presented.