The effects of delta9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat.
The effects of delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on hydroxylation of estradiol and testosterone in rat liver microsomes were investigated. Acute and chronic treatment of male and female rats with either cannabinoid, 2 or 10 mg/kg, significantly elevated steroid hydroxylase activity. Acute administration of THC or CBD, 10 mg/kg, evoked no detectable changes in cytochrome P-450 levels, but a significant decrease in those of cytochrome b5. Chronic administration of THC or CBD, 2 mg/kg, decreased levels of cytochrome P-450, whereas cytochrome b5 levels appeared normal. Acute doses of THC or CBD at 10 mg/kg significantly depressed testosterone formation in testis microsomes. Chronic THC, 2 mg/kg, but not CBD, evoked the most dramatic decrease in testicular enzyme activity.
D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure; D013739:Testosterone / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors
D002186:Cannabinoids; D003580:Cytochromes; D012739:Gonadal Steroid Hormones; D002185:Cannabidiol; D013739:Testosterone; D004958:Estradiol; D013759:Dronabinol; D003577:Cytochrome P-450 Enzyme System