Cannabis sativa has been used for centuries throughout human history for both its psychoactive effects and medicinal properties. Cytochrome P450s (CYP) are drug metabolizing enzymes that are involved in the metabolism of a wide variety of xenobiotics. Therefore, studying the metabolism of cannabinoids by CYPs is critical to understand their pharmacology. As cannabis is often consumed in conjunction with other drugs, there is a high potential for drug-cannabis interactions. Previously, it has been shown that selected cannabinoids are CYP inhibitors that remains to be studied systematically. Additionally, CYPs polymorphisms may lead to inter-individual variability in cannabis metabolism which remains to be evaluated. Therefore, the primary focus of the talk will be to delineate the biochemical mechanism of the metabolism of selected minor cannabinoids such as cannabigerol (CBG) and cannabichromene (CBC) by the primary selected human liver CYPs – CYP3A4, CYP2D6, CYP2C9, CYP2J2 and CYP2C8. Furthermore, we will present the information on the initial pharmacology of minor cannabinoid CYP metabolites with respect to inflammation, cannabinoid receptor activation and TRP channel activation.<br/>Cannabigerol (CBG) and cannabichromene (CBC) are non-psychoactive phytocannabinoids. They are associated with multiple beneficial health effects. Although CBG and CBC metabolism has been studied previously, but the role of Cytochrome P450 (CYPs) in affecting the rate of product formation are yet to be explored. Here we report the formation of CBG and CBC metabolites in presence of liver CYPs like 2J2, 3A4, 2D6 and 2C8 along with 2C9 and liver microsomes. Metabolism studies indicate that rate of the metabolite formation differs between the different CYPs. CBG and CBC metabolites shows greater efficiency against inflammation and their interactions with the cannabinoid receptors and TRP channels are varied which indicates that they will have different effects on pain modulation. In additional to metabolism, we have also unveiled about cannabinoid-drug interactions through inhibition of critical CYP enzymes. Overall, given the recent legalization of marijuana and its increasing therapeutic use in cancer and epileptic patients, and its world-wide recreational use, the consideration of minor cannabinoid-elicited drug-interactions is essential. The knowledge in this work will be the primary research that will be presented.

Minor phytocannabinoid metabolism by cytochrome P450s

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.