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Cannabinol (CBN) was also mainly metabolized to 11-hydroxy-CBN and 8-hydroxy-CBN by the microsomes. The 11-hydroxylation of three cannabinoids by the microsomes was markedly inhibited by sulfaphenazole, a selective inhibitor of CYP2C enzymes, while the hydroxylations at the 7α-(Δ8-THC), 8β-(Δ9-THC) and 8-positions (CBN) of the corresponding cannabinoids were highly inhibited by ketoconazole, a selective inhibitor of CYP3A enzymes. Human CYP2C9-Arg expressed in the microsomes of human B lymphoblastoid cells efficiently catalyzed the 11-hydroxylation of Δ8-THC (7.60 nmol/min/nmol CYP), Δ9-THC (19.2 nmol/min/nmol CYP) and CBN (6.62 nmol/min/nmol CYP). Human CYP3A4 expressed in the cells catalyzed the 7α-(5.34 nmol/min/nmol CYP) and 7β-hydroxylation (1.39 nmol/min/nmol CYP) of Δ8-THC, the 8β-hydroxylation (6.10 nmol/min/nmol CYP) and 9α,10α-epoxidation (1.71 nmol/min/nmol CYP) of Δ9-THC, and the 8-hydroxylation of CBN (1.45 nmol/min/nmol CYP). These results indicate that CYP2C9 and CYP3A4 are major enzymes involved in the 11-hydroxylation and the 8-(or the 7-) hydroxylation, respectively, of the cannabinoids by human hepatic microsomes. 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These results indicate that CYP2C9 and CYP3A4 are major enzymes involved in the 11-hydroxylation and the 8-(or the 7-) hydroxylation, respectively, of the cannabinoids by human hepatic microsomes. In addition, CYP3A4 is a major enzyme responsible for the 7α- and 7β-hydroxylation of Δ8-THC, and the 9α,10α-epoxidation of Δ9-THC.","study.pubmedId":17303175,"study.embaseId":null,"study.croIdentifier":"HU","study.croInformation":"Hokuriku University","study.dateStart":null,"study.dateEnd":null,"study.internalComment":null,"study.status":"published","study.compoundId":null,"study.naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProductSampleId":null,"study.studySourceTypeId":1,"study.naturalProduct.uid":"NP-0162af79-839e-40e2-af47-361c659061e9","study.naturalProduct.binomial":"Cannabis 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These results indicate that CYP2C9 and CYP3A4 are major enzymes involved in the 11-hydroxylation and the 8-(or the 7-) hydroxylation, respectively, of the cannabinoids by human hepatic microsomes. 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