Spectral interaction of 11-hydroxy-.DELTA.8-tetrahydrocannabinol with rabbit and rat liver microsomal cytochrome P-450.

Abstract
11-Hydroxy-.DELTA.8-tetrahydrocannabinol, which is an active metabolite of .DELTA.8-tetrahydrocannabinol, produced a spectral change on interacting with liver microsomes of rabbits and rats (.lambda.max 395 nm; .lambda.min 428 nm). The apparent dissociation constants (Ks) were 402.1 and 76.6 .mu.M for microsomes of untreated rabbits and rats, respectively. Pretreatment with phenobarbital enhanced the spectral change caused by 11-hydroxy-.DELTA.8-tetrahydrocannabinol with microsomes of both species, and increased the cytochrome P-450 content. 11-Hydroxy-.DELTA.8-tetrahydrocannabinol interfered with the spectral change caused by .DELTA.8-tetrahydrocannabinol or hexobarbital, but not with that caused by aniline. 11-Hydroxy-.DELTA.8-tetrahydrocannabinol is metabolized by the microsomal monooxygenase system involving cytochrome P-450.