Decarbonylation: A metabolic pathway of cannabidiol in humans

Abstract

Cannabidiol (CBD) is a non‐psychoactive cannabinoid, which is of growing medical interest. Previous studies on the metabolism of CBD showed mainly the formation of hydroxylated or oxidized derivatives, the formation of carboxylic acids or modifications of the aliphatic side chain. Using incubation of CBD with hepatic microsomes of mice, the formation of carbon monoxide was reported. We investigated the phase I metabolism of CBD and cannabidivarin (CBDV) using in vitro experiments with human liver microsomes in order to discover so far not considered metabolites. Identification of metabolites was done by liquid chromatography coupled with quadrupole time of flight mass spectrometry (LC−QToF−MS). Within these experiments, we came across decarbonylation of CBD and CBDV. Further investigations were focused on observed decarbonylated CBD (DCBD). To confirm this metabolite in humans in vivo, plasma samples containing large amounts of cannabinoids as well as serum and urine samples, collected after a voluntary intake of a CBD‐containing food supplement, were analyzed by LC coupled to triple quadrupole mass spectrometry (LC−QQQ−MS). DCBD was detected in in vitro incubation mixtures, serum samples, and urine samples (after alkaline or enzymatic hydrolysis) collected after the voluntary intake, as well as in plasma samples of cannabis users. DCBD appears to be an important supplementary human metabolite that might be helpful for the analytical confirmation of a CBD uptake and might improve the interpretation of the consumption of CBD‐containing products. Results of this study indicate a prolonged detectability of DCBD (in serum) in comparison to CBD after oral CBD ingestion.

The Interplay between the Endocannabinoid System, Epilepsy and Cannabinoids

“…The cannabinoids and their metabolites can be detected and measured in a variety of biological fluids, like blood plasma [147], saliva, and urine [148] to evaluate their intake and study their metabolism [149]. Therefore, a suite of different types of epileptic and neuroinflammatory biomarkers (especially the downstream mediators, such as IL-1β and COX-2 products) in conjunction with biomarkers of cannabinoid treatment (e.g., cannabinoids and their metabolites) could help to paint a more complete picture of the cannabinoids’ metabolic pathways, their toxicity, and their modes of action on the neuroinflammatory pathways.…”

Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer

“…CBD is known to have antitumor activity against Noxa activation, inhibition of mTOR/cyclin D1, and G-protein-coupled receptors/mitogen-activated protein kinase pathway in various cancers such as pancreatic 3,4 , glioblastoma 1 , colorectal 5 , and breast cancer 6 . It also has beneficial effects on brain function, metabolism, and pain reduction 7–9 . However, there have been few reports on the anticancer mechanism by CBD in gastric cancer.…”

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

“…However, multiomics analysis has shown that CBD penetrates cell membranes, altering the chemical activity of cholesterol and increasing lipid order [ 59 ]. Cannabidiol is biotransformed in the liver, where decarbonylated CBD (DCBD) and 7-hydroxycannabidiol (7-OH-CBD) [ 60 , 61 ], observed in our study, are produced by cytochrome P450 (CYP) isoenzymes. 7-OH-CBD is known to be one of the metabolites of CBD generated by CYP2C19 of liver microsomes [ 61 ] and this study showed its level increases in the liver membrane fraction after UVA/UVB irradiation.…”