Human brain microsomes: their abilities to metabolize tetrahydrocannabinols and cannabinol

In spite of the psychedelic action of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) in the brain, no report on its metabolism by human brain microsomes has been published. In this study, the metabolism of Δ 8 -THC, Δ 9 -THC and cannabinol (CBN) was studied using human brain microsomes. The metabolites formed were analyzed by gas chromatography–mass spectrometry after trimethylsilylation. The three cannabinoids were biotransformed to two main metabolites by human brain microsomes. Δ 8 - and Δ 9 -THCs were mainly oxidized at the allylic positions. The main metabolites of Δ 8 -THC were 7α-hydroxy- and 11-hydroxy-Δ 8 -THCs, whereas those of Δ 9 -THC were 8α-hydroxy- and 11-hydroxy-Δ 9 -THCs. CBN was metabolized to 8-hydroxy- and 11-hydroxy-CBNs. Although the primary metabolic pathways of the THCs and CBN in brain microsomes are different from those in liver microsomes for other mammalian species, those in human brain microsomes were similar to those in human liver microsomes.