9 alpha, 10 alpha-epoxyhexahydrocannabinol formation from delta 9-tetrahydrocannabinol by liver microsomes of phenobarbital-treated mice and its pharmacological activities in mice.

9 alpha, 10 alpha-Epoxyhexahydrocannabinol (9 alpha, 10 alpha-EHHC) was found to be formed from delta 9-tetrahydrocannabinol (delta 9-THC) by liver microsomes of mice pretreated with phenobarbital. Further, pharmacological effects of 9 alpha, 10 alpha-EHHC in mice were compared with those of delta 9-THC using catalepsy, hypothermia, pentobarbital-induced sleep prolongation and anti-convulsant activity against pentylenetetrazol as indices. 9 alpha, 10 alpha-EHHC was approximately equipotent with delta 9-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 9 alpha, 10 alpha-EHHC can contribute to the pharmacological effects of delta 9-THC as an active metabolite.