Effects of four cannabinoids [cannabidiol (CBD), Δ8-tetrahydrocannabinol, Δ9-tetrahydrocannabinol, and cannabinol] on hepatic microsomal oxidation of testosterone (17β-hydroxy-androst-4-ene-3-one) were examined in adult male rats. Only CBD (30 μM) competitively inhibited 2α-hydroxy-testosterone (2α-OH-T) and 16α-OH-T formation by hepatic microsomes but did not affect androstenedione (androst-4-ene-3, 17-dione) and 7α-OH-T formation. Kinetic analyses demonstrated that the inhibitory profile of CBD for testosterone oxidation was different from those of SKF 525-A, which caused competitive inhibition for 2α- and 16α-hydroxylations and noncompetitive inhibition for 6α-hydroxylation, and of metyrapone, which inhibited only 6β-hydroxylation competitively. CBD also suppressed formation of 2α-OH-T, 16α-OH-T, and androstenedione from testosterone, catalyzed by a reconstituted system containing hepatic cytochrome P-450 purified from phenobarbital-treated rats. Pretreatment of the rat with CBD (10 mg/kg, ip, once a day for 3 days) decreased testosterone oxidation at the 2α-, 16α-, and 17-positions and increased 7α-OH-T formation, while total cytochrome P-450 content was decreased. These results suggest that CBD suppresses hepatic testosterone oxidation at the 2α-, 16α-, and 17-positions through selective inhibition of the male-specific cytochrome P-450 in the adult male rat.
|Number of pages||10|
|Journal||Drug Metabolism and Disposition|
|Publication status||Published - Dec 1 1988|
ASJC Scopus subject areas
- Pharmaceutical Science