Epoxide-diol pathway of delta 1-THC in the rat in vitro.

1. 1 alpha, 2 alpha-Epoxyhexahydrocannabinol was identified as a metabolite of delta 1-tetrahydrocannabinol. 2. The two trans-1,2-dihydroxyhexahydrocannabinol isomers, 1 alpha, 2 beta-dihydroxyhexahydrocannabinol and 1 beta, 2 alpha-dihydroxyhexahydrocannabinol (as their acetates) were tentatively identified as metabolites from incubation of 1 alpha, 2 alpha-epoxyhexahydrocannabinol with rat hepatic microsomes in vitro. 3. The 1 alpha, 2 alpha-epoxyhexahydrocannabinol acetate was found to be a good substrate for epoxide hydratase as compared to styrene oxide. 4. The synthesis of metabolites of 1 alpha, 2 alpha-epoxyhexahydrocannabinol is described.