What is CBG?

What is CBG? What is Cannabigerol (CBG)?

Cannabis has been used for thousands of years due to the many opportunities the plant carries. It is only in recent times that scientists have begun to give the cannabinoids, and their descendants, the attention they deserve. The mechanisms of the molecules were an unsolved mystery until tetrahydrocannabinol (THC) and the first cannabinoid receptor, CB1, were discovered, followed by endocannabinoids, anandamides (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG). The AEA, 2-AG and CB receptors have been regrouped and classified by physiologists in the endocannabinoid system (ECS).

ECS is a complex network of neurotransmitters and receptors that work together to signal and transmit information throughout the body. They modulate essential neurovegetative functions and help maintain the body's homeostasis. AEA is most often tonic signaling agents for ECS and regulates synaptic transmissions, while 2-AG acts as a phasic signal activator in neuronal depolarization and mediator of synaptic plasticity.

Phytocannabinoids are terpenophenolic compounds that naturally occur in cannabis plants. Among them are not only the psychoactive tetrahydrocannabinol (THC), but also several non-psychoactive molecules such as cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC) and many more. CBG-type molecules are the natural precursors of cannabinoids, and have shown, through several independent studies, to have therapeutic properties and are therefore promising tools in developing current therapies for a wide range of disorders. We are determined to inform the scientific community about the latest developments in the research of CBG's properties and therapeutic capabilities.

Cannabis has been used for thousands of years due to the many opportunities the plant carries. It is only in recent times that scientists have begun to give the cannabinoids, and their descendants, the attention they deserve. The mechanisms of the molecules were an unsolved mystery until tetrahydrocannabinol (THC) and the first cannabinoid receptor, CB1, were discovered, followed by endocannabinoids, anandamides (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG). The AEA, 2-AG and CB receptors have been regrouped and classified by physiologists in the endocannabinoid system (ECS).

ECS is a complex network of neurotransmitters and receptors that work together to signal and transmit information throughout the body. They modulate essential neurovegetative functions and help maintain the body's homeostasis. AEA is most often tonic signaling agents for ECS and regulates synaptic transmissions, while 2-AG acts as a phasic signal activator in neuronal depolarization and mediator of synaptic plasticity.

Phytocannabinoids are terpenophenolic compounds that naturally occur in cannabis plants. Among them are not only the psychoactive tetrahydrocannabinol (THC), but also several non-psychoactive molecules such as cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC) and many more. CBG-type molecules are the natural precursors of cannabinoids, and have shown, through several independent studies, to have therapeutic properties and are therefore promising tools in developing current therapies for a wide range of disorders. We are determined to inform the scientific community about the latest developments in the research of CBG's properties and therapeutic capabilities.

Phytocannabinoids and synthetic substitutes

The isolation of CBG was first discovered in 1964 when Y. Gaony reported the structure and parts of the synthesis of many cannabinoids, including CBG. Although CBG is represented in most types of cannabis (though only in relatively small quantities), researchers have concentrated their energy on the more prominent cannabinoids, THC and CBD. In contrast to naturally occurring cannabinoids, synthetic cannabinoid-inspired compounds, which have become leading drugs in the pharmaceutical market, have been invented in recent decades. Some of these chemically modified cannabinoids do not have the psychoactive effects that THC has, but at the same time have some of the therapeutic properties of already known cannabinoids. It is important to point out that synthetic drugs often have poor side effects, due to solvent residues. Since we are dealing with very new compounds, the side effects can be drastic and, in extreme cases, fatal. By contrast, the cannabinoids, used for recreational use and with therapeutic effect, have been for an incredibly long time - and no life-threatening cases have ever been reported.

Phytocannabinoids such as CBD, CBN and CBG contain most of the therapeutic effects of THC, without being psychoactive. These cannabinoids have been shown to be effective against a growing number of diseases and conditions. Although positive results are seen, treatment is very limited for the population. Furthermore, while many scientific and medical studies use CBD, CBG is not used yet, as it is being investigated and tested.

The biochemistry behind CBG

As we mentioned before, CBG was first isolated by Y. Gaoni, in 1964, when he was able to show the structure and parts of the synthesis of many cannabinoids, including CBG. CBG is a terpenophenolic compound and, like many other cannabinoids, may be divided into three distinct parts. The components not only carry different chemical and pharmaceutical properties, but also influence the absorption potential of the molecules in different ways. The hydrophilic moiety is represented by a phenolic ring believed to carry the antibacterial and antimicrobial properties of the cannabinoids. The ring is joined by two lipophilic chains at each of their diagonal ends. One is the n-alkyl chain, while the other is represented by a terpenoic function that contains therapeutic powers and appears to be related to many of the medical properties of CBG. By having two lipophilic moieties, CBG, like other cannabinoids, has a very difficult time dissolving in water, while it is very readily absorbable by cell membranes and tissues.

As you already know, CBG is the natural precursor for THC, CBD and CBN. CBG's phenolic moieties are probably created via the polyketide method, where a triketo acid can bear some of the responsibility. Its cyclization leads to olivetoic acid, which turns into C-acylate of geranyl diphosphate, based on the CBGa synthase. The carboxylic acid form of this phytocannabinoid, cannabigerolic acid (CBGa), is very important for the synthesis of other phytocannabinoids, and it is exactly this chemical form that phytocannabinoids have when they are in fresh cannabis plants. The corresponding cannabinoids are subsequently absorbed through decarboxylation (heat) (Figure 1). The conversion from CBG acid to THC, CBD and CBN acid is also catalyzed by specific enzymes, and is called THC, CBD and CBN acid synthase.

CBG and its therapeutic effects

Despite relatively few in-depth studies of CBG, there is evidence of pharmacological action by a number of targets. CBG has been shown to have relatively weak agonistic effects at CB1 (Ki 440 nM) and CB2 (Ki 337 nM), which explains the non-psychotropic properties of the molecule. However, it affects the endocannabinoid tone by preventing the escalation of AEA and therefore greater levels of AEA. Older studies point to CBG as a gamma amino butyric acid (GABA) escalator, in a range of affinity comparable or superior to THC or CBD, which may explain its anti-anxiety and muscle relaxant properties. In 1991, Evans and his colleagues found that CBG offers analgesic and antiarrhythmic effects, by blocking lipoxygenase activity and thus reducing the risk of inflammation to a greater extent than conventional medicine. CBG has also been shown to be useful as anti-depressant and anti-hypertensive drugs on rodents. Most of the effects mentioned are mediated by their potent activity as? -2 adrenoreceptor agonists and by their moderate conductive binding conditions against 5-HT1A. In addition, CBG inhibits keratinocyte proliferation, which appears to be useful in psoriasis, and combined with being a relatively potent TRPM8 antagonist, leads to the possibilities of alleviating prostate cancer and bladder pain. Recently, CBG has been proven to be an effective cytotoxic molecule in human epithelioid carcinoma, as well as the second most effective phytocannabinoid, just after CBD, against breast cancer. CBG has also demonstrated its antibacterial and antimicrobial properties (including methicillin-resistant staphylococcal aureus, MRSA), to have moderate antifungal effects.

Numerous studies have shown evidence of CBG for enhanced efficacy when associated with terpenoids. Terpenoids are quite potent and can affect animals and human behavior if only slightly inhaled through the air. They show unique therapeutic effects that can contribute to many of the medicinal effects of cannabis extract. For example, limonene has been shown to synergize with both CBG and CBD by promoting apoptosis in breast cancer cells, whereas Myrcene, a terponide known from hops, synergizes with CBG and CBD by inhibiting hepatic carcinogenesis aflatoxin induced. Linalool, a terpenoid known from lavender, appears to work with CBD and CBG in the treatment of anxiety. In addition, CBC and CBG have been shown to have cooperative properties in collaboration with the terpenoid, caryophylene oxide, which is naturally found in lemon balm as a fungicide, and with effect similar commercial fungicidal products such as sulconazole and ciclopiroxolamine. CBGa has been shown to have synergy with the lemon balm terpenoids as CBGa keeps the insects away and ensures that the plant is not eaten, suggesting that CBGa may be a promising alternative for protecting crops and vegetables from insects and parasites.

Perspectives

CBG has shown promising results in many treatments. Unfortunately, CBG with a relatively low concentration in the plant, resulting in therapeutic administration of CBG oil, will be limited by the amount of compound obtained from plant extraction.

However, recent breeding work has shown that cannabis chemotypers - with their lack of downstream enzymes - phytocannabinoid content is 100% CBG. After 9 years of hard work and breeding programs, Endoca has created a CBG oil and 99% CBG insulation. That being said, more studies and studies are needed before one can confirm and determine the wide range of therapeutic properties that CBG oil contains.

  1. DEVANE, W. et al. Determination of Rat Brain and Characterization of a Cannabinoid Receptor in Rat Brain. Moth. Pharmacol. 34, 605–613 (1988).
  2. Devane, W. et al. Isolation and Structure of Brain Constituent that Binds to the Cannabinoid Receptor. Science (80-.). 258, 1946-1949 (1992).
  3. Mechoulam, R. et al. Identification Present in Canine Gut, That Binds To Cannabinoid Receptors. 50, 83–90 (1995).
  4. Pertwee, RG & Ross, RA Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fat. Acids 66, 101–121 (2002).
  5. Russo, EB Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 1, 154–165 (2016).
  6. Mahmoud, A. Marijuana and the Cannabinoids. (Humana Press, 2007).
  7. Russo, EB Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol. 163, 1344–1364 (2011).
  8. Turner, SE, Williams, CM, Iversen, L. & Whalley, BJ Molecular Pharmacology of Phytocannabinoids. (2017). doi: 10.1007 / 978-3-319-45541-9
  9. Gaoni, Y. & Mechoulam, R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. J. Am. Chem. Soc 86, 1646–1647 (1964).
  10. Mbvundula, EC, Rainsford, KD & Bunning, RA Cannabinoids in pain and inflammation. Inflammopharmacology 12, 99–114 (2004).
  11. Iseger, TA & Bossong, MG A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr. Res. 162, 153–161 (2015).
  12. Devinsky, O. et al. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsy 55, 791–802 (2014).
  13. Elsohly, MA, Radwan, MM, Gul, W., Chandra, S. & Galal, A. Phytocannabinoids. 103, (2017).
  14. Pertwee, RG Endocannabinoids. (Springer US, 2015).
  15. Leo, A., Russo, E. & Elia, M. Cannabidiol and epilepsy: Rational and therapeutic potential. Pharmacol. Res. 107, 85–92 (2016).
  16. Whiting, PF et al. Cannabinoids for Medical Use: A Systematic Review and Meta-Analysis. Jama 313, 2456–2473 (2015).
  17. Wierzbicki, AS Rimonabant: Endocannabinoid inhibition for the metabolic syndrome. Int. J. Clin. Pract. 60, 1697–1706 (2006).
  18. Tai, S. & Fantegrossi, WE Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential. Curr Addict Rep. 1, 129–136 (2014).
  19. Gurney, S., Scott, K., Kacinko, S., Presley, B. & Logan, B. Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugs. Forensic Sci Rev. 26, 53–78 (2014).
  20. Moreira, FA & Crippa, JAS The psychiatric side effects of rimonabant. Rev. Bras. Psiquiatr. 31, 145–53 (2009).
  21. Rosenthal, E. & Kubby, S. Why Marijushould be Legal. (Running Press, London, 1996).
  22. Appendino, G. et al. Antibacterial Cannabinoids from Cannabis sativa ?: A Structure - Activity Study. J. Nat. Prod. 71, 1427–1430 (2008).
  23. Fellermeier, M. & Zenk, M.H. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett. 427, 283–285 (1998).
  24. Zirpel, B., Stehle, F. & Kayser, O. Production of ??? 9-tetrahydrocannabinolic acid from cannabigerolic acid by whole cells of Pichia (Komagataella) pastoris expressing ??? 9-tetrahydrocannabinolic acid synthase from Cannabis sativa l. Biotechnol . Lett. 37, 1869–1875 (2015).
  25. Gauson, LA et al. Cannabigerol is retained as a partial agonist at both CB1 and CB2 receptors. Symp. Cannabinoids 26 June-1 July 206 (2007).
  26. Banebjee, SP, Mechoulam, S. & Snydeji, H. Cannabinoids: influence in neurotransmitter uptake Influence in Rat brain synaptosomes. J. Pharmacol. Exp. Ther. 194, 74–81 (1975).
  27. Kargmanss, S., Prasitn, P. & Evans, J. F. Translocation of HL-60 Cell 5 Lipoxygenase. (1991).
  28. Milman, G. et al. N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties. PNAS 103, 2428–2433 (2006).
  29. Evelyn, A., Formukong, A., Evans, T. & Evans, FJ Inhibition of the cataleptic effect of tetrahydrobannabinol by other constituents of Cannabis Sativa L. Jo. Pharm. Pharmacol. 40, 132–134 (1985).
  30. Cascio, MG, Gauson, LA, Stevenson, LA, Ross, RA & Pertwee, RG Evidence that the plant cannabinoid cannabigerol is a highly potent? 2-adrenoceptor agonist and moderately potent 5HT 1A receptor antagonist. Br. J. Pharmacol. 159, 129–141 (2010).
  31. Wilkinson, JD & Williamson, EM Cannabinoids inhibit human keratinocyte proliferation through a non-CB1 / CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J. Dermatol. Sci. 45, 87–92 (2007).
  32. Ortar, G. et al. (-) - Menthylamine derivatives as potent and selective antagonists of transient receptor potential melastatin type-8 (TRPM8) channels. Bioorganic Med. Chem. Lett. 20, 2729–2732 (2010).
  33. Mukerji, G., Yiangou, Y., Agarwal, S.K. & Anand, P. Transient receptor potential vanilloid receptor subtype 1 in painful bladder syndrome and its correlation with pain. J. Urol. 176, 797–801 (2006).
  34. SH1, B. et al. Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Arch Pharm Res. 21, 353–356 (1998).
  35. Ligresti, A. et al. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J. Pharmacol. Exp. Ther. 318, 1375–1387 (2006).
  36. Eisohly, HN, Turner, CE, Clark, AM & Eisohly, MA Synthesis and Anti-Microbial Activities of Certain Cannabichromene and Cannabigerol Related-Compounds. J. Pharm. Sci. 71, 1319-1323 (1982).
  37. Petrocellis, L. et al. Effects of cannabinoids and cannabinoid-enriched cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163, 1479–1494 (2011).
  38. DM, V. et al. Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I / II Clinical Trials Committee. Cancer Chemother Pharmacol. 42, 111–117 (1998).
  39. De-oliveira, ACAX, Ribeiro-pinto, LF, Otto, SS & Gonc, A. Induction of liver monooxygenases by i -myrcene. Toxicology 124, 135–140 (1997).
  40. L, R. et al. Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain. Mini Rev Med Chem. 16, 721–728 (2016).
  41. D, Y., L, M., JP, C. & J., M.-C. Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis. Mycopathologia 148, 79–82 (1999).
  42. De Meijer, EPM & Hammond, KM The inheritance of chemical phenotype in Cannabis sativa L. (II): Cannabigerol predominant plants. Euphytica 145, 189–198 (2005).

Do you have questions?

We are ready to help you - whether it's supplements, or quality of life.