In vivo metabolism of the ethyl homologues of delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in the mouse.
Ethyl-delta-8-tetrahydrocannabinol (ethyl-delta-8-THC) and ethyl-delta-9-THC were synthesized by condensation of 5-ethyl-1,3-dihydroxybenzene and 1S-cis-verbenol. The two cannabinoids were administered to male Charles River CD-1 mice and hepatic metabolites were extracted with ethyl acetate and isolated by chromatography on Sephadex LH-20. Metabolite identification was by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS, methyl ester/TMS and dihydro/TMS derivatives. Metabolites from ethyl-delta-8-THC, of which six were identified, were similar with respect to the positions substituted on the terpene ring to those produced by higher homologues; the major metabolite, accounting for about 95% of the metabolic fraction, was ethyl-delta-8-THC-11-oic acid. Side-chain hydroxy metabolites were not detected. Metabolism of ethyl-delta-9-THC was also similar to that of the higher homologues with the exception that less metabolism occurred at C-8 and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Five metabolites were identified; minor metabolites were mainly dihydroxylated compounds and hydroxylated derivatives of ethyl-delta-9-THC-11-oic acid. A dihydro-metabolite, the C-9-axial-COOH isomer of ethyl-hexahydrocannabinol-11-oic acid, was produced by both compounds and a trace of ethyl-CBN-11-oic acid was produced by ethyl-delta-9-THC.
Brown
N K
NK
University Department of Pharmacology, Oxford, UK.
Harvey
D J
DJ
D000818:Animals; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice
C070807:ethyl-delta-9-tetrahydrocannabinol; C070806:ethyl-delta-8-tetrahydrocannabinol; D013759:Dronabinol