Phytocannabinoid Sources - Defining Cannabis Cannabinoids
Updated: Jun 17
Brought to you by the Higher Learning LV Cannabis for Anxiety seminar.
Welcome to Higher Learning LV's Cannabis Conclusions series, where you learn more in less time.
Cannabis Cannabinoids Study
A 2016 study entitled "Phytocannabinoids: A Unified Critical Inventory" that was published in the journal Natural Product Reports from the Royal Society of Chemistry reported that the term "cannabinoid" has become increasingly vague. It explained that discoveries of alternate sources of cannabinoids and cannabinoid-like molecules in botanical species other than cannabis requires a shift in the language used to describe them.
"Originally coined in a phytochemical context to refer to a structurally homogenous class of meroterpenoids typical of cannabis (Cannabis sativa L.), the name 'cannabinoid' has then been associated to the biological profile of the psychotropic constituent of marijuana (Δ9-THC), substantially losing its structural meaning and being growingly associated, in accordance with the rules of pharmacological research, to compounds showing affinity to the two GPCR known as cannabinoid receptors (CB1 and CB2), independently from any structural or biogenetic relationship with the cannabis meroterpenoids," reported the study.
"Phytocannabinoids have a limited distribution in Nature, but occur in phylogenetically unrelated sources (higher plants, liverworts, fungi)."
Cannabis Cannabinoids Study Conclusion
The conclusion section for this study appears below.
"Phytocannabinoids have a limited distribution in Nature, but occur in phylogenetically unrelated sources (higher plants, liverworts, fungi). These compounds are traditionally associated to cannabis, that, with almost 150 alkyl (C-5, C-3, C-1) phytocannabinoids reported, remains their main source of diversity.
"However, only a few members of the class are accumulated in substantial amounts, namely the ones having the terpenyl residue in the form of a geranyl (CBG-type), a menthyl (CBD-type and THC-type), or a prenylchromanyl (CBC-type) residue. Many of the minor cannabinoids could be auto-oxidation artifacts eventually evolving into aromatized phytocannabinoid of the CBN type, but others might be genuine natural products worth investigating from a bioactivity standpoint.
"Apart from the variation of the terpenyl connectivity, structural diversity in phytocannabinoids is also related to the elongation of the isoprenyl moiety from a terpenyl- to a sesquiterpenyl moiety, while shortened analogues (hemiprenyl phytocannabinoids) have only been reported in phytocannabinoids from the aralkyl series. Oxidation of the resorcinyl moiety to a quinol is also documented, but compounds of this type have only been isolated in their acetylated and more stable form. The mammalian metabolism of phytocannabinoids involves allylic oxidation rather than nuclear oxidation to quinoid metabolites, but, due to this instability, these metabolites might have been overlooked.
"It is tempting to predict that, given the biosynthetic plasticity of C. sativa, further types of alkyl phytocannabinoids will be described in the near future."
"O-Methylation was reported in phytocannabinoids obtained from far-East samples of cannabis but it is otherwise rare in alkyl phytocannabinoids, while it is common in compounds from the phenethyl series. Aralkyl cannabinoids have a broader distribution in Nature compared to alkyl cannabinoids, but their accumulation is point-like in terms of producing organisms, with phenethyl substitution prevailing in liverworts and styryl substitution in plant constituents.
"Most phytocannabinoids still await an evaluation of their biological profile and pharmaceutical potential, a somewhat paradoxical observation in the light of the enormous interest for the pharmacological activity of phytocannabinoids and the messianic await for the development of cannabinoid-based medicines that permeates the media.
"It is tempting to predict that, given the biosynthetic plasticity of C. sativa, further types of alkyl phytocannabinoids will be described in the near future from both the natural and the man-induced diversity of cannabis strains. In the wake of the growing interest from amorfrutins, further additions to the phytocannabinoids inventory should also come from compounds of the aralkyl structural type.
"By focusing on the remarkable structural diversity of phytocannabinoids and highlighting their largely overlooked wide distribution in plants, we hope to stimulate the exploration of the biological space associated to their natural variation."
"By focusing on the remarkable structural diversity of phytocannabinoids and highlighting their largely overlooked wide distribution in plants, we hope to stimulate the exploration of the biological space associated to their natural variation, going beyond the THC structural motif, and paving the way to a full opening of the Pandora's box of their biomedical potential."
View the original study.
Are you a cannabis industry professional? Check out Higher Learning LV's Deep Dive Subscription that features dozens of long-form articles based on the latest peer-reviewed scientific research. Priced to accommodate personal and enterprise training budgets.