title: Plasma and brain levels of delta 6-THC and seven monooxygenated metabolites correlated to the cataleptic effect in the mouse.
abstract: The brain and plasma levels of unchanged delta 6-tetrahydrocannabinol (delta 6-THC), 7-hydroxy-delta 6-THC, the five side-chain hydroxylated delta 6-THC derivatives and 1 alpha, 2 alpha-epoxyhexahydrocannabinol (EHHC) were correlated to the cataleptic effect in the mouse up to 60 min. after intravenous administration of radiolabelled compounds in the range 1.3 to 12.4 mg/kg. All cannabinoids except delta 6-THC and 1"-hydroxy-delta 6-THC showed a very good correlation between brain/plasma concentrations and cataleptic effect. 4"-Hydroxy-and "1-hydroxy-delta 6-THC reached the highest concentration in the brain but the most potent cannabinoids were delta 6-THC, 7-hydroxy-, 3"-hydroxy-delta 6-THC, and EHHC followed by 5"-hydroxy-, 4"-hydroxy-, 2"-hydroxy-, and 1"-hydroxy-delta 6-THC in decreasing order. It was concluded that structural rather than pharmacokinetic features are most important in determining the psychoactivity of the various cannabinoid metabolites of THC.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced*; D013759:Dronabinol / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D010084:Oxidation-Reduction
chemical_list: D002186:Cannabinoids; D013759:Dronabinol