Dioxygenated metabolites of cannabidiol formed by rat liver.
The metabolism of cannabidiol (CBD) was studied in vitro using a 10 000 g supernatant from rat liver. After removal of unchanged CBD and its monohydroxylated metabolites, a polar fraction remained from which ten dioxygenated metabolites were isolated. Mass spectrometry and nuclear magnetic resonance spectroscopy were used to identify the following metabolites: 6,7-dihydroxy-CBD, 1 inch,7-dihydroxy-CBD, 3 inch,7-dihydroxy-CBD, 4 inch,7-dihydroxy-CBD, 5 inch,7-dihydroxy-CBD, 2 inch,6-dihydroxy-CBD, 3 inch,6beta-dihydroxy-CBD, 4 inch, 6beta-dihydroxy-CBD (tentative), 3 inch-hydroxy-6-oxo-CBD, and 4 inch-hydroxy-6-oxo-CBD. The abundance of isolated dihydroxy metabolites reflected the quantity of monohydroxy metabolites that was previously found. In both series, 7-hydroxylation occurred to the greatest extent. Side chain hydroxylation occurred predominantly at C-4 inch and to a lesser degree at C-3 inch. Trace amounts of metabolites were hydroxylated at C-1 inch,-2 inch, or 5 inch.
D000818:Animals; D002185:Cannabidiol / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism*; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D006900:Hydroxylation; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
D002186:Cannabinoids; D002185:Cannabidiol