Identification of in vivo liver metabolites of delta 1-tetra-hydrocannabinol, cannabidiol, and cannabinol produced by the guninea-pig.

The metabolites of delta 1-tetrahydroannabinol (delta 1-THC), cannabidiol (CBD), and cannabinol (CBN) produced in vivo by the guinea-pig have been studed by combined gas-liquid chromatography-mass spectrometry, 45 metabolites of delta 1-THC were identified of which 12 have not been reported before. Several other metabolites were detected but not identified. The major metabolic routes involved allylic and aliphatic hydroxylations, oxidations to ketones and acids, oxidative degradation of the side-chain presumably by the beta-oxidation pathway, and formation of glucuronide conjugates. Di- and tri-substituted metabolites were abundant. The metabolism differed considerably from that observed in mouse and rat in that 1''- and 6 beta-hydroxylation and oxidation degradation of the side-chain were major metabolic pathways. 1''-Hydroxy-delta 1-THC was found as a pair of diasteroisomers. Similar metabolic pathways were observed with CBD; twenty metabolites were identified of which two were new. Only 6 metabolites of CBN were identified. These mainly mono-substituted in the same positions as were observed with delta 1-THC and CBD.