Identification and Characterization of Cannabichromene's Major Metabolite Following Incubation with Human Liver Microsomes

Authors

Alexandra M Ward
Touraj Shokati
Jost Klawitter
Jelena Klawitter
Vu Nguyen
Laura Kozell
Atheir I Abbas
David Jones
Uwe Christians

Publication Date

6-13-2024

Journal

Metabolites

Abstract

Cannabichromene (CBC) is a minor cannabinoid within the array of over 120 cannabinoids identified in the Cannabis sativa plant. While CBC does not comprise a significant portion of whole plant material, it is available to the public in a purified and highly concentrated form. As minor cannabinoids become more popular due to their potential therapeutic properties, it becomes crucial to elucidate their metabolism in humans. Therefore, the goal of this was study to identify the major CBC phase I-oxidized metabolite generated in vitro following incubation with human liver microsomes. The novel metabolite structure was identified as 2′-hydroxycannabicitran using gas chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. Following the identification, in silico molecular modeling experiments were conducted and predicted 2′-hydroxycannabicitran to fit in the orthosteric site of both the CB1 and CB2 receptors. When tested in vitro utilizing a competitive binding assay, the metabolite did not show significant binding to either the CB1 or CB2 receptors. Further work necessitates the determination of potential activity of CBC and the here-identified phase I metabolite in other non-cannabinoid receptors.

Keywords

cannabichromene, 2′-hydroxycannabicitran, cannabicitran, human drug metabolism, phase I metabolism, human liver microsomes, gas chromatography–mass spectrometry, nuclear magnetic resonance spectroscopy, molecular docking, CB1 receptor, CB2 receptor, binding

Comments

Supplementary Materials

PMID: 38921465