This review is concerned primarily with our recent papers which have been published or presented since 1978. Especially, metabolic conversion of Δ
8-THC to Δ
8-THC-11-oic acid and to 8α, 9α-epoxyhexahydrocannabinol (8α, 9α-EHHC) and their pharmacological implications are described. Liver microsomes catalyze formation of 11-OH-Δ
8-THC from Δ
8-THC, 11-oxo-Δ
8-THC from 11-OH-Δ
8-THC, and 8α, 9α-EHHC from Δ
8-THC. The involvement of cytochrome P-450 in these reactions were suggested in vivo as well as in vitro. 11-OH-Δ
8-THC was detected and determined as a metabolite in vivo of Δ
8-THC in the liver and brain of mice. 11-OH-Δ
8-THC, when administered to mice, showed higher distribution in the brain as compared with Δ
8-THC. Pharmacological activities of 11-OH-Δ
8-THC, 11-oxo-Δ
8-THC, Δ
8-THC-11-oic acid, 8α, 9α-EHHC, 8β, 9β-EHHC, 9α, 10α-EHHC and 8β, 9α-di OH-HHC were compared with that of Δ
8-THC using mice. Pharmacological effect of 11-OH-Δ
8-THC, 11-oxo-Δ
8-THC, 8β, 9β-EHHC and 9α, 10α-EHHC were more potent than that of Δ
8-THC in the cataleptogenic, hypothermic, pentobarbital-induced sleep prolonging, and anticonvulsant effects. Daily administration of 11-OH-Δ
8-THC or 11-oxo-Δ
8-THC as well as Δ
8-THC quickly induced tolerance to their hypothermic and pentobarbital-induced sleep-prolonging effects. The LD
50s of 11-OH-Δ
8-THC, 11-oxo-Δ
8-THC and Δ
8-THC-11-oic acid are larger than that of Δ
8-THC.
View full abstract