Receptors and molecular properties
CBG can be found in cannabis plants and some analogue forms of CBG can be found in the Helichrysum umbraculigerum plant (Pollastro et al., 2018).
CBG binds to both CB1 and CB2 receptors, having higher affinity for CB2 (Navarro et al., 2018; Rosenthaler et al., 2014).
CBG, as well as CBD, is a NAV channel blocker but did not show anticonvulsant effects (Hill et al., 2014).
CBG activates α2-adrenoceptors and CB2 and blocks CB1 and 5-HT1A receptors (Cascio, Gauson, Stevenson, Ross, & Pertwee, 2010).
Also, CBG activates TRPA1, TRPV1 and TRPV2, antagonizes TRPM8 and inhibits ACU. Botanical drug substance (BDS) containing CBD also inhibits MAGL and NAAA. These receptor interactions suggest that CBG could have analgesic, anti-inflammatory and anti-cancer properties (De Petrocellis et al., 2011, 2008).
CBG anologues also actívate TRPA1 (Lopatriello et al., 2018).
CBG modulates GPR55 (Morales, Hurst, & Reggio, 2017).
Δ9-THC, Δ8-THC, CBN, CBD, CBG, and CBC are directly metabolized by CYP2J2 and inhibit human cardiac CYP2J2 (Arnold, Weigle, & Das, 2018)
CBG has antifungal and antibacterial properties (Eisohly, Turner, Clark, & Eisohly, 1982).
CBG shows anti-inflammatory properties (Petrosino et al., 2018), counteracts oxidative stress through CB2 receptors in macrophages (Giacoppo et al., 2017) and shows neuroprotective and anti-inflammatory effects for NSC-34 motor neurons by reducing caspase 3 activation, Bax expression, IL-1β, TNF-α, IFN-γ, PPARγ, nitrotyrosine, SOD1 and iNOS protein levels (Gugliandolo, Pollastro, Grassi, Bramanti, & Mazzon, 2018).
The CBG quinone derivative VCE-003.2 has neuroprotective effects against an animal model of amyotrophic lateral sclerosis (Rodríguez-Cueto et al., 2018) and animal and cell models of parkinsons disease (García et al., 2018).
CBG inhibits platelet aggregation, which increases bleeding time and reduces thromboembolism (Formukong, Evans, & Evans, 1989).
CBG causes hyperphagia in animals without producing negative neuromotor side effects (Brierley, Samuels, Duncan, Whalley, & Williams, 2016). Also, CBG-BDS acts as an appetite stimulant, probably through CB1 receptors (Brierley, Samuels, Duncan, Whalley, & Williams, 2017).
CBG inhibits cellular growth in human oral epitheloid carcicoma cells (Baek et al., 1998) and in leukaemic cells (Scott, Shah, Dalgleish, & Liu, 2013) and showed chemopreventive, curative and pro-apoptotic effects against colorectal cancer cells in vitro and in vivo models through TRPM8 and CB2 receptors (Borrelli et al., 2014). CBG would act more effectively agianst leukaemic cells if it would be mixed with CBD (Scott, Dalgleish, & Liu, 2017; Scott et al., 2013).
CBG/CBGA as well as CBD/CBDA extracts reduced aldose reductase activity in vivo, suggesting a potential effect on Diabetes (Smeriglio et al., 2018).
CBG and related cannabinoids may have therapeutic potential for the treatment of glaucoma (Colasanti, 1990). Chronic administration of CBG causes ocular hypotensive effects without any toxic effects (Colasanti, Powell, & Craig, 1984). Also, its analog CBG-DMH reduces intraocular pressure (Szczesniak, Maor, Robertson, Hung, & Kelly, 2011).
CBG reduces acetylcholine-induced contractions in the bladder, suggesting a potential effect to treat bladder disorders (Pagano et al., 2015).
CBG can activate α2 receptors and block CB1 and 5-HT1A receptors (Cascio et al., 2010), suggesting CBG does have therapeutic potential in the treatment of depression.
Functional Gastro-Intestinal Disorders
Apart from THC, (relatively) non-psychotropic cannabinoids such as THCV, CBD and CBG were found to have anti-inflammatory effects in experimental intestinal inflammation (Alhouayek & Muccioli, 2012). CBG attenuates colitis in animal models, reduces nitric oxide production in macrophages and reduces ROS formation in intestinal epithelial cells, showing therapeutic potential to treat gastrointestinal inflammation (Borrelli et al., 2013).
CBG counteracts the anti-nausea effects produced by THC or CBD, probably due to the activation of 5-HT1A receptor (Rock et al., 2011). This is important to avoid CBG when looking for anti-nausea and anti-vomiting effects of cannabinoids.
CBG improved motor deficits and had neuroprotective effects in animal models of Huntington´s Disease through the modulation of pro-inflammatory markers, reactive microgliosis and improved antioxidant defenses. CBG also normalized gene expression altered in those animal models (Valdeolivas et al., 2015).
The interaction between CBG and the α2 receptor (alpha 2 adrenalin receptor) may prove effective in pain control (Giovannoni, Ghelardini, Vergelli, & Dal Piaz, 2009).
CBG could be used to treat psoriasis (Wilkinson & Williamson, 2007) and it shows potential to treat dry-skin syndrome by increasing sebaceous lipid synthesis (Oláh et al., 2016). Also, CBG, as well as CBD, are involved in skin cell proliferation and differenciation, which can have an effect in skin diseases (Pucci et al., 2013)
Alhouayek, M., & Muccioli, G. G. (2012). The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends in Molecular Medicine, 18(10), 615-625. https://doi.org/10.1016/j.molmed.2012.07.009
Arnold, W. R., Weigle, A. T., & Das, A. (2018). Cross-talk of Cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2. Journal of Inorganic Biochemistry, 184, 88-99. https://doi.org/10.1016/j.jinorgbio.2018.03.016
Baek, S. H., Kim, Y. O., Kwag, J. S., Choi, K. E., Jung, W. Y., & Han, D. S. (1998). Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Archives of Pharmacal Research, 21(3), 353-356.
Borrelli, F., Fasolino, I., Romano, B., Capasso, R., Maiello, F., Coppola, D., … Izzo, A. A. (2013). Beneficial effect of the non-psychotropic plant Cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochemical Pharmacology, 85(9), 1306-1316. https://doi.org/10.1016/j.bcp.2013.01.017
Borrelli, F., Pagano, E., Romano, B., Panzera, S., Maiello, F., Coppola, D., … Izzo, A. A. (2014). Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic Cannabinoid. Carcinogenesis, 35(12), 2787-2797. https://doi.org/10.1093/carcin/bgu205
Brierley, D. I., Samuels, J., Duncan, M., Whalley, B. J., & Williams, C. M. (2016). Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats. Psychopharmacology, 233(19-20), 3603-3613. https://doi.org/10.1007/s00213-016-4397-4
Brierley, D. I., Samuels, J., Duncan, M., Whalley, B. J., & Williams, C. M. (2017). A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT]9-tetrahydrocannabinol, elicits hyperphagia in rats. Behavioural Pharmacology. https://doi.org/10.1097/FBP.0000000000000285
Cascio, M. G., Gauson, L. A., Stevenson, L. A., Ross, R. A., & Pertwee, R. G. (2010). Evidence that the plant Cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. British Journal of Pharmacology, 159(1), 129-141. https://doi.org/10.1111/j.1476-5381.2009.00515.x
Colasanti, B. K. (1990). A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol. Journal of Ocular Pharmacology, 6(4), 259-269.
Colasanti, B. K., Powell, S. R., & Craig, C. R. (1984). Intraocular pressure, ocular toxicity and neurotoxicity after administration of delta 9-tetrahydrocannabinol or cannabichromene. Experimental Eye Research, 38(1), 63-71.
De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., … Di Marzo, V. (2011). Effects of cannabinoids and Cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology, 163(7), 1479-1494. https://doi.org/10.1111/j.1476-5381.2010.01166.x
De Petrocellis, L., Vellani, V., Schiano-Moriello, A., Marini, P., Magherini, P. C., Orlando, P., & Di Marzo, V. (2008). Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. The Journal of Pharmacology and Experimental Therapeutics, 325(3), 1007-1015. https://doi.org/10.1124/jpet.107.134809
Eisohly, H. N., Turner, C. E., Clark, A. M., & Eisohly, M. A. (1982). Synthesis and antimicrobial activities of certain cannabichromene and cannabigerol related compounds. Journal of Pharmaceutical Sciences, 71(12), 1319-1323.
Formukong, E. A., Evans, A. T., & Evans, F. J. (1989). The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation. The Journal of Pharmacy and Pharmacology, 41(10), 705-709.
García, C., Gómez-Cañas, M., Burgaz, S., Palomares, B., Gómez-Gálvez, Y., Palomo-Garo, C., … Fernández-Ruiz, J. (2018). 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. Journal of Neuroinflammation, 15(1), 19. https://doi.org/10.1186/s12974-018-1060-5
Giacoppo, S., Gugliandolo, A., Trubiani, O., Pollastro, F., Grassi, G., Bramanti, P., & Mazzon, E. (2017). Cannabinoid CB2 receptors are involved in the protection of RAW264.7 macrophages against the oxidative stress: an in vitro study. European Journal of Histochemistry: EJH, 61(1), 2749. https://doi.org/10.4081/ejh.2017.2749
Giovannoni, M. P., Ghelardini, C., Vergelli, C., & Dal Piaz, V. (2009). Alpha2-agonists as analgesic agents. Medicinal Research Reviews, 29(2), 339-368. https://doi.org/10.1002/med.20134
Gugliandolo, A., Pollastro, F., Grassi, G., Bramanti, P., & Mazzon, E. (2018). In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid. International Journal of Molecular Sciences, 19(7). https://doi.org/10.3390/ijms19071992
Hill, A. J., Jones, N. A., Smith, I., Hill, C. L., Williams, C. M., Stephens, G. J., & Whalley, B. J. (2014). Voltage-gated sodium (NaV) channel blockade by plant cannabinoids does not confer anticonvulsant effects per se. Neuroscience Letters, 566, 269-274. https://doi.org/10.1016/j.neulet.2014.03.013
Lopatriello, A., Caprioglio, D., Minassi, A., Schiano Moriello, A., Formisano, C., De Petrocellis, L., … Taglialatela-Scafati, O. (2018). Iodine-mediated cyclization of cannabigerol (CBG) expands the Cannabinoid biological and chemical space. Bioorganic & Medicinal Chemistry, 26(15), 4532-4536. https://doi.org/10.1016/j.bmc.2018.07.044
Morales, P., Hurst, D. P., & Reggio, P. H. (2017). Molecular Targets of the Phytocannabinoids: A Complex Picture. Progress in the Chemistry of Organic Natural Products, 103, 103-131. https://doi.org/10.1007/978-3-319-45541-9_4
Navarro, G., Varani, K., Reyes-Resina, I., Sánchez de Medina, V., Rivas-Santisteban, R., Sánchez-Carnerero Callado, C., … Franco, R. (2018). Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1-CB2 Heteroreceptor Complexes. Frontiers in Pharmacology, 9, 632. https://doi.org/10.3389/fphar.2018.00632
Oláh, A., Markovics, A., Szabó-Papp, J., Szabó, P. T., Stott, C., Zouboulis, C. C., & Bíró, T. (2016). Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment. Experimental Dermatology, 25(9), 701-707. https://doi.org/10.1111/exd.13042
Pagano, E., Montanaro, V., Di Girolamo, A., Pistone, A., Altieri, V., Zjawiony, J. K., … Capasso, R. (2015). Effect of Non-psychotropic Plant-derived cannabinoids on Bladder Contractility: Focus on Cannabigerol. Natural Product Communications, 10(6), 1009-1012.
Petrosino, S., Verde, R., Vaia, M., Allarà, M., Iuvone, T., & Di Marzo, V. (2018). Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis. The Journal of Pharmacology and Experimental Therapeutics, 365(3), 652-663. https://doi.org/10.1124/jpet.117.244368
Pollastro, F., De Petrocellis, L., Schiano-Moriello, A., Chianese, G., Heyman, H., Appendino, G., & Taglialatela-Scafati, O. (2018). Reprint of: Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum. Fitoterapia, 126, 35-39. https://doi.org/10.1016/j.fitote.2018.04.002
Pucci, M., Rapino, C., Di Francesco, A., Dainese, E., D’Addario, C., & Maccarrone, M. (2013). Epigenetic control of skin differentiation genes by phytocannabinoids. British Journal of Pharmacology, 170(3), 581-591. https://doi.org/10.1111/bph.12309
Rock, E. M., Goodwin, J. M., Limebeer, C. L., Breuer, A., Pertwee, R. G., Mechoulam, R., & Parker, L. A. (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(3), 505-512. https://doi.org/10.1007/s00213-010-2157-4
Rodríguez-Cueto, C., Santos-García, I., García-Toscano, L., Espejo-Porras, F., Bellido, Ml., Fernández-Ruiz, J., … de Lago, E. (2018). Neuroprotective effects of the cannabigerol quinone derivative VCE-003.2 in SOD1G93A transgenic mice, an experimental model of amyotrophic lateral sclerosis. Biochemical Pharmacology. https://doi.org/10.1016/j.bcp.2018.07.049
Rosenthaler, S., Pöhn, B., Kolmanz, C., Nguyen Huu, C., Krewenka, C., Huber, A., … Moldzio, R. (2014). Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures. Neurotoxicology and Teratology, 46, 49-56. https://doi.org/10.1016/j.ntt.2014.09.003
Scott, Katherine A., Dalgleish, A. G., & Liu, W. M. (2017). Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration. International Journal of Oncology, 51(1), 369-377.
Scott, Katherine Ann, Shah, S., Dalgleish, A. G., & Liu, W. M. (2013). Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules. Anticancer Research, 33(10), 4373-4380.
Smeriglio, A., Giofrè, S. V., Galati, E. M., Monforte, M. T., Cicero, N., D’Angelo, V., … Circosta, C. (2018). Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol. Fitoterapia, 127, 101-108. https://doi.org/10.1016/j.fitote.2018.02.002
Szczesniak, A.-M., Maor, Y., Robertson, H., Hung, O., & Kelly, M. E. M. (2011). Nonpsychotropic cannabinoids, abnormal cannabidiol and canabigerol-dimethyl heptyl, act at novel Cannabinoid receptors to reduce intraocular pressure. Journal of Ocular Pharmacology and Therapeutics: The Official Journal of the Association for Ocular Pharmacology and Therapeutics, 27(5), 427-435. https://doi.org/10.1089/jop.2011.0041
Valdeolivas, S., Navarrete, C., Cantarero, I., Bellido, M. L., Muñoz, E., & Sagredo, O. (2015). Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics, 12(1), 185-199. https://doi.org/10.1007/s13311-014-0304-z
Wilkinson, J. D., & Williamson, E. M. (2007). cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of Psoriasis. Journal of Dermatological Science, 45(2), 87-92. https://doi.org/10.1016/j.jdermsci.2006.10.009