9α,10α-Epoxyhexahydrocannabinol formation from Δ9-tetrahydrocannabinol by liver microsomes of phenobarbital-treated mice and its pharmacological activities in mice

9α,10α-Epoxyhexahydrocannabinol (9α,10α-EHHC) was found to be formed from Δ⁹-tetrahydrocannabinol (Δ⁹-THC) by liver microsomes of mice pretreated with phenobarbital. Further, pharmacological effects of 9α,10α-EHHC in mice were compared with those of Δ⁹-THC using catalepsy, hypothermia, pentobarbital-induced sleep prolongation and anticonvulsant activity against pentylenetetrazol as indices. 9α,10α-EHHC was approximately equipotent to Δ⁹-THC in the pharmacological indices except for catalepsy. The cataleptogenic effect of the epoxide was about 4 times as potent as the parent compound. From these results, it is suggested that 9α,10α-EHHC can contribute to the pharmacological effects of Δ⁹-THC as an active metabolite.