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Cannabigerol: The Cannabinoid Progenitor


The phytocannabinoid, cannabigerolic acid (CBGA) which converts into cannabigerol (CBG, figure 1),  is known as the “progenitor cannabinoid” or “the mother of all cannabinoids” through which most other naturally occurring cannabinoids are derived. This article aims to examine the history of CBG as well as its interactions with the endocannabinoid system and its documented effects on the body.

Figure 1. Cannabigerol Chemical Structure

The History of CBG

For thousands of years, Cannabis Sativa has been used and cultivated as early as 2700 BCE in Eurasian countries for medicinal, ritualistic, and textile purposes (1). While unknown at the time, C. Sativa contained the compounds of what are now called cannabinoids. As scientific research developed, specific cannabinoids have been isolated and identified. CBG was first isolated and identified in 1964 by Y. Gaoni and R. Mechoulam (2) along with other cannabinoids like CBD and THC (3). Despite the slow progression in research due to prohibition of the plant in the 20th century, it has been found that most of the naturally occurring cannabinoids are derived from CBGA. CBGA is the first cannabinoid formed and then through metabolic processes and other factors like heat and degradation over time, produces other cannabinoids. Currently, CBG is not recognized as a controlled substance by the United Nations from the Convention on Psychotropic Substances of 1971 (4). In the United States with the Hemp Farming Act of 2018, hemp-derived cannabinoids (this includes CBG, CBD, CBN, etc.) are legal with the restriction that the THC content is below 0.3% on a dry-weight basis (6).

The Chemistry of CBG

CBG is a phytocannabinoid which are naturally occurring cannabinoid compounds in the Cannabis Sativa plant (7). Phytocannabinoids follow a similar enzymatic pathway (8) of production as shown in figure 2 below. Starting off with hexanoyl-coenzyme a (9), an enzyme called tetraketide synthase (TKS) adds a total of 3 malonyl-coenzyme a (10). Another enzyme called olivetolic acid cyclase (OAC) appropriately converts the molecule to olivetolic acid (11). Lastly an enzyme called aromatic prenyltransferase adds geranyl pyrophosphate onto olivetolic acid, converting it to CBGA (12).

Figure 2. The Simplified Biosynthesis of CBGA 

With the biosynthesis of CBGA complete, the biosynthesis of other cannabinoids can occur as shown in figure 3 below (8).

Figure 3. Simplified Biosynthesis of Various Cannabinoids with their Appropriate Synthases

Once CBGA has been decarboxylated (13, figure 4) into CBG, it can interact with the endocannabinoid system much like THC and CBD. The endocannabinoid system contains receptors,CB1 and CB2 receptors, that produce effects on the body when activated. The CB1 receptors are mainly located in the brain, while the CB2 receptors are located throughout the body mainly in the liver and lungs (14). For the CB2 receptor, CBG acts as a partial agonist (15) on the CB2 receptor. CBG binds to the CB2 receptor and activates it, producing the same effects on the body as the naturally produced endocannabinoid like anandamide (16). CBG has a much weaker affinity and binding (17) to the CB1 receptor than other cannabinoids making it a poor agonist.It is still able to activate the receptor and produce an effect, but is easily beaten out by other competing molecules (18). In addition to the CB receptors, it has been found that CBG can bind to activate the α2-adrenoceptors, which is responsible for muscle contraction, sedation, and other various effects on the central nervous system. α2-adrenoceptors also block the 5HT1A which is responsible for serotonin reuptake and maintaining other homeostasis processes within the body (19).

Figure 4. The decarboxylation of CBGA to CBG

The Effects of CBG

Not much research has been done on the supposed effects of CBG on the body compared to cannabinoids like CBD and THC; however, there are some supported benefits of CBG. It has been shown that CBG has neuroprotective properties in treatments for neurodegenerative diseases such as Huntington’s disease or Parkinson’s disease by helping to reduce neuroinflammation and improving motor deficits in mice (20). CBG may have potential to help with gastrointestinal diseases such as inflammatory bowel disease by increasing the rate of tissue recovery and reducing inflammation in mice (21). Some studies have shown that cannabinoids, like CBG, can have antibacterial properties such as inhibiting the InhA enzyme (22) in certain bacteria and can even inhibit the functions of antibiotic resistant bacteria, both studies were done in vitro or in a laboratory setting and not in living organisms (23).

Testing CBG Products

CBG, in the United States, is not regulated by the Food and Drug Administration (FDA) and it’s important to know what exactly is in the products that are on the market (24). When purchasing a CBG product, make sure that there is a Certificate of Analysis (COA) from an accredited third-party laboratory associated with that specific product, meaning that if the label claim is 1000mg per bottle, the COA will confirm that the label is correct. These COAs are usually found as a scannable QR code on the product itself or on the distributor/manufacturer’s website. Shopping for CBG products can also be overwhelming with everything out there on the market.Try to avoid products that do not have a certificate of analysis or have statements that claim their products may treat, cure, or prevent ailments. Know that there is still research being done to learn more about any potential effects and health benefits CBG can provide. Currently, these supposed benefits are not recognized by the FDA. 

Ionization Labs can quantify the results of CBG and CBGA while distinguishing it from other cannabinoids that might be present, as shown below (figure 5) in our method.

Figure 5. CBG, CBGA, and their neighhbor analytes on a chromatograph

Our Cannabinoid Testing Services are able to test the potency of CBG in products you develop or buy from a manufacturer. You can get verified and accurate results in as little as 24 hours! Any comments or questions about testing can be directed to labservices@ionizationlabs.com or call us at 737-231-0772. In addition to our Cannabinoid Testing Services, we also offer CannID, an in-house testing solution for quality assurance/quality control during the product development cycle for our customers that manufacture their own products.

References:

  1. (PDF) The pharmacological history of cannabis
  2. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish
  3. Cannabidiol: What is CBD?
  4. CONVENTION ON PSYCHOTROPIC SUBSTANCES, 1971
  5. The Controlled Substances Act
  6. 115th Congress (2017-2018): Hemp Farming Act of 2018
  7. Phytocannabinoids: Origins and Biosynthesis: Trends in Plant Science
  8. The biosynthesis of the cannabinoids | Journal of Cannabis Research | Full Text
  9. Hexanoyl-coenzyme a | C27H46N7O17P3S - PubChem
  10. malonyl-CoA | C24H38N7O19P3S - PubChem
  11. Olivetolic acid | C12H16O4 - PubChem
  12. Geranyl diphosphate | C10H20O7P2 - PubChem
  13. Decarboxylation: What Is It and Why Is It Important?.
  14. Endocannabinoid System: What Is It & How Does It Work? - Sensi Seeds
  15. Psychology blog: Agonists and antagonists - Pamoja.
  16. Anandamide | C22H37NO2 - PubChem
  17. In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
  18. Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes - PMC
  19. Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist
  20. Neuroprotective Properties of Cannabigerol in Huntington's Disease: Studies in R6/2 Mice and 3-Nitropropionate-lesioned Mice - PMC
  21. Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease
  22. In Silico Repositioning of Cannabigerol as a Novel Inhibitor of the Enoyl Acyl Carrier Protein (ACP) Reductase (InhA) | HTML
  23. Uncovering the Hidden Antibiotic Potential of Cannabis | ACS Infectious Diseases
  24. FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD) | FDA

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