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sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the antinociceptive effect were 14.1 and 39.4, respec- tively. The present study demonstrated that CBD can be converted to ∆ 9 -THC and its related cannabinoids, 9α- OH-HHC and 8-OH-iso-HHC, in artifi cial gastric juice, and that these HHCs show ∆ 9 -THC-like effects in mice, although their pharmacological effects were less potent than those of ∆ Abstract Cannabidiol (CBD), a nonpsychoactive can- nabinoid, was found to be converted to 9α-hydroxy- hexahydrocannabinol (9α-OH-HHC) and 8-hydroxy- iso-hexahydrocannabinol (8-OH-iso-HHC) together with ∆ 9 -tetrahydrocannabinol (∆ 9 -THC), a psychoactive cannabinoid, and cannabinol in artifi cial gastric juice. These cannabinoids were identifi ed by gas chromatogra- phy-mass spectrometry (GC-MS) by comparison with the spectral data of the authentic compounds. Pharma- cological effects of 9α-OH-HHC and 8-OH-iso-HHC in mice were examined using catalepsy, hypothermia, pen- tobarbital-induced sleep prolongation, and antinocicep- tion against acetic acid-induced writhing as indices. The ED50 values (effective dose producing a 50% reduction of control; mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso- HHC for the cataleptogenic effect were 8.0 and 30.4, re- spectively. 8-OH-iso-HHC (10 mg/kg, i.v.) produced a signifi cant hypothermia from 15 to 90 min after admin- istration, although 9α-OH-HHC failed to induce such an effect at the same dose. However, both HHCs (10 mg/ kg, i.v.) signifi cantly prolonged pentobarbital-induced

Metabolism of cannabinol (CBN) was studied in vitro using hepatic microsomes from human livers. The metabolites formed were analyzed by thinlayer chromatography (TLC) and identified by gas chromatography-mass spectrometry as their trimethylsilyl derivatives. 11-Hydroxy-CBN, the major metabolite, was detected together with a smaller amount of another mono-hydroxylated metabolite. The minor metabolite was identified as 8-hydroxy-CBN, after comparing its Rf value by TLC, retention time by GC, and the mass spectrum with those of the authentic compound. 8-Hydroxy-CBN was confirmed to be a new metabolite of CBN formed by human hepatic microsomes.