Dioxygenated metabolites of cannabidiol formed by rat liver

Abstract

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″,7-dihydroxy-CBD, 3″,7-dihydroxy-CBD, 4″,7-dihydroxy-CBD, 5″,7-dihydroxy-CBD, 2″,6-dihydroxy-CBD, 3″,6β-dihydroxy-CBD, 4″,6β-dihydroxy-CBD (tentative), 3″-hydroxy-6-oxo-CBD, and 4″-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″ and to a lesser degree at C-3″. Trace amounts of metabolites were hydroxylated at C-1″, -2″, or 5″.