Spectral Interaction of 11-Hydroxy-Δ⁸-tetrahydrocannabinol with Rabbit and Rat Liver Microsomal Cytochrome P-450

Abstract

11-Hydroxy-Δ⁸-tetrahydrocannabinol, which is an active metabolite of Δ⁸-tetrahydrocannabinol, produced a spectral change on interacting with liver microsomes of rabbits and rats (λ_max 395 nm ; λ_min 428 nm). The apparent dissociation constants (Ks) were found to be 402.1 and 76.6 μM for microsomes of untreated rabbits and rats, respectively. Pretreatment with phenobarbital enhanced the spectral change caused by 11-hydroxy-Δ⁸-tetrahydrocannabinol with microsomes of both species, as well as increasing the cytochrome P-450 content. Furthermore, 11-hydroxy-Δ⁸-tetrahydrocannabinol interfered with the spectral change caused by Δ⁸-tetrahydrocannabinol or hexobarbital, but not with that caused by aniline. These results are consistent with the view that 11-hydroxy-Δ⁸-tetrahydrocannabinol is further metabolized by the microsomal monooxygenase system involving cytochrome P-450.