Potency and safety analysis of hemp-derived delta-9 products: The hemp vs. cannabis demarcation problem

Clinical data
ATC code
  • None
Legal status
Legal status
  • US: Unscheduled
  • 2-[(2E)-3,7-Dimethylocta-2,6-dienyl]-5-pentyl-benzene-1,3-diol
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.346.098 Edit this at Wikidata
Chemical and physical data
Molar mass316.485 g·mol−1
3D model (JSmol)
  • Oc1cc(cc(O)c1C/C=C(\C)CC\C=C(/C)C)CCCCC
  • InChI=1S/C21H32O2/c1-5-6-7-11-18-14-20(22)19(21(23)15-18)13-12-17(4)10-8-9-16(2)3/h9,12,14-15,22-23H,5-8,10-11,13H2,1-4H3/b17-12+ checkY
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Biosynthesis of cannabigerol

Cannabigerol (CBG) is one of more than 120 identified cannabinoid compounds found in the plant genus Cannabis.[1][2] Cannabigerol is the decarboxylated form of cannabigerolic acid, the parent molecule from which other cannabinoids are synthesized.[3][4]

Cannabigerol is normally a minor constituent of cannabis.[3][5] During plant growth, most of the cannabigerol is converted into other cannabinoids, primarily tetrahydrocannabinol (THC) or cannabidiol (CBD), leaving about 1% cannabigerol in the plant.[6] Some strains, however, produce larger amounts of cannabigerol and cannabigerolic acid, while having low quantities of other cannabinoids, like THC and CBD.[7]

Although cannabigerol is sold as a dietary supplement, its effects and safety for human consumption are undefined.[3]


The biosynthesis of cannabigerol begins by loading hexanoyl-CoA onto a polyketide synthase assembly protein and subsequent condensation with three molecules of malonyl-CoA.[8] This polyketide is cyclized to olivetolic acid via olivetolic acid cyclase, and then prenylated with a ten carbon isoprenoid precursor, geranyl pyrophosphate, using an aromatic prenyltransferase enzyme, geranyl-pyrophosphate—olivetolic acid geranyltransferase, to biosynthesize cannabigerolic acid, which can then be decarboxylated to yield cannabigerol.[3][5]


As of 2021, no clinical research has been conducted to test the specific effects of cannabigerol in humans.[3] Cannabigerol is under laboratory research to determine its pharmacological properties and potential effects in disease conditions, with no conclusions about therapeutic effects or safety, as of 2021.[3][9][10]

Cannabigerol has affinity and activity at CB1 and CB2 cannabinoid receptors in vitro.[3][9] It appears to be unique among cannabinoid compounds by also having high affinity and activity at α2 adrenergic receptors and moderate activity at serotonin 5-HT1A receptors.[3][11]

Safety concerns

Although general effects of its use as a dietary supplement remain undefined, the activity of cannabigerol at α2 adrenergic receptors in vitro raises concerns about its safety for human consumption, possibly having unintended effects, such as bradycardia, arterial hypotension, and dry mouth.[3]

FDA warning letters for dietary supplements

As of 2022, the US Food and Drug Administration has issued numerous warning letters to American companies for illegally marketing cannabis supplement products,[12] including one selling cannabigerol products with unproven illegal claims of efficacy against the COVID-19 virus and inflammation.[13]

Legal status

Cannabigerol is not scheduled by the UN Convention on Psychotropic Substances.[citation needed] In the United States, cannabigerol derived from marijuana is illegal under the Controlled Substances Act, while cannabigerol derived from hemp is legal, as long as the hemp THC content is less than 0.3% of dry weight.[12][14]

In Switzerland, it is legal to produce hemp rich in cannabigerol as a tobacco substitute, as long as its THC content remains below 1.0%.[15]

See also


  1. ^ ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A (2017). "Phytochemistry of Cannabis sativa L". Phytochemistry of Cannabis sativa L. Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 1–36. doi:10.1007/978-3-319-45541-9_1. ISBN 978-3-319-45539-6. PMID 28120229.
  2. ^ Turner SE, Williams CM, Iversen L, Whalley BJ (2017). "Molecular Pharmacology of Phytocannabinoids". Phytocannabinoids. Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 61–101. doi:10.1007/978-3-319-45541-9_3. ISBN 978-3-319-45539-6. PMID 28120231.
  3. ^ a b c d e f g h i Nachnani R, Raup-Konsavage WM, Vrana KE (2021). "The pharmacological case for cannabigerol". The Journal of Pharmacology and Experimental Therapeutics. 376 (2): 204–212. doi:10.1124/jpet.120.000340. ISSN 0022-3565. PMID 33168643. S2CID 226296897.
  4. ^ "Cannabigerol; ID 5315659". PubChem, National Library of Medicine, US National Institutes of Health. 2 July 2022. Retrieved 7 July 2022.
  5. ^ a b Morales P, Reggio PH, Jagerovic N (2017). "An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol". Frontiers in Pharmacology. 8: 422. doi:10.3389/fphar.2017.00422. PMC 5487438. PMID 28701957.
  6. ^ Aizpurua-Olaizola O, Soydaner U, Öztürk E, Schibano D, Simsir Y, Navarro P, et al. (February 2016). "Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes". Journal of Natural Products. 79 (2): 324–331. doi:10.1021/acs.jnatprod.5b00949. PMID 26836472.
  7. ^ Zagožen M, Čerenak A, Kreft S (2021-09-01). "Cannabigerol and cannabichromene in Cannabis sativa L." Acta Pharmaceutica. 71 (3): 355–364. doi:10.2478/acph-2021-0021. PMID 36654096. S2CID 231543630.
  8. ^ Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE (July 2012). "Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides". Proceedings of the National Academy of Sciences of the United States of America. 109 (31): 12811–12816. Bibcode:2012PNAS..10912811G. doi:10.1073/pnas.1200330109. PMC 3411943. PMID 22802619.
  9. ^ a b Morales P, Hurst DP, Reggio PH (2017). "Molecular Targets of the Phytocannabinoids: A Complex Picture". Phytocannabinoids. Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 103–131. doi:10.1007/978-3-319-45541-9_4. ISBN 978-3-319-45539-6. PMC 5345356. PMID 28120232.
  10. ^ Couch DG, Maudslay H, Doleman B, Lund JN, O'Sullivan SE (March 2018). "The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis". Inflammatory Bowel Diseases. 24 (4): 680–697. doi:10.1093/ibd/izy014. PMID 29562280.
  11. ^ Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG (January 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. doi:10.1111/j.1476-5381.2009.00515.x. PMC 2823359. PMID 20002104.
  12. ^ a b "FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)". US Food and Drug Administration. 21 January 2021. Retrieved 7 July 2022.
  13. ^ Ashley D (28 March 2022). "Warning Letter to Greenway Herbal Products LLC; Ref. 627042". Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration. Retrieved 7 July 2022.
  14. ^ "USC > Title 21 > Chapter 13 > Subchapter I > Part A > § 802. Definitions: (16)" (PDF). Government Publishing Office - US Code. 2016.
  15. ^ BAG, Bundesamt für Gesundheit. "Häufig gestellte Fragen (FAQ) zu Tabakersatzprodukten mit THC-armem Hanf mit CBD". www.bag.admin.ch (in German). Retrieved 2022-07-06.