Oxidative metabolism of Δ9-tetrahydrocannabinol (THC), one of the major components of marihuana, was studied using liver microsomes of adult male and female rats. There was no significant difference in the rates of the cannabinoid oxidation in terms of nmol per min per nmol of liver microsomal cytochrome P450 or of nmol per min per mg of microsomal protein between male and female rats. Δ9-THC was biotransformed to various metabolites including 11-hydroxy-Δ9-THC (11-OH-Δ9-THC), 8α-OH-Δ9-THC, 8α,11-diOH-Δ9-THC, 3′-OH-Δ9-THC by liver microsomes of male rats, while it was oxidized selectively to 11-OH-Δ9-THC by liver microsomes of female rats. After intraperitoneal administration of Δ9-THC, various metabolites were again found in the liver of the male rat, while in the female rat oxidation of the methyl group at the 9-position was a major metabolic pathway. These results demonstrate that an apparent sex-related difference exists in the oxidative metabolism of Δ9-THC in the rat.
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