Metabolites of cannabidiol identified in human urine.
1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.
Harvey
D J
DJ
University Department of Pharmacology, Oxford, UK.
Mechoulam
R
R
D001711:Biotransformation; D002185:Cannabidiol / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D002186:Cannabinoids / Q000378:metabolism*; D004421:Dystonia / Q000188:drug therapy / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000652:urine; D006801:Humans; D015394:Molecular Structure
D002186:Cannabinoids; D005965:Glucuronates; D002185:Cannabidiol