Sex Difference in the Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Pentobarbital-Induced Sleeping Time and Hepatic Microsomal Drug Metabolizing Enzyme Systems in Mice

HAMAJIMA KOICHI, WATANABE KAZUHITO, NARIMATSU SHIZUO, TATEOKA YUJI, YAMAMOTO IKUO, YOSHIMURA HIDETOSHI

doi:10.1248/yakushi1947.103.12_1289

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大麻主成分Δ9-Tetrahydrocannabinol(Δ9-THC)およびCannabidiol(CBD)のPentobarbital睡眠および肝薬物代謝酵素系に及ぼす影響-マウスにおける性差
大麻主成分Δ9-Tetrahydrocannabinol(Δ9-THC)およびCannabidiol(CBO)のPentobarbital睡眠および肝薬物代謝酵素系に及ぼす影響--マウスにおける性差
タイマシュセイブンデルタ9 Tetrahydrocannabinol デル
Sex Difference in the Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Pentobarbital-Induced Sleeping Time and Hepatic Microsomal Drug Metabolizing Enzyme Systems in Mice

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Abstract

Effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD) on pentobarbital (PB)-induced sleeping time and on hepatic microsomal drug metabolizing enzyme systems were studied in male and female mice. 1) In all i.p. doses used (10, 50 and 100 mg/kg), Δ⁹-THC and CBD significantly prolonged PB-induced sleeping time in both sexes of mice. CBD was more active than Δ⁹-THC in this route of administration. 2) Δ⁹-THC prolonged PB-induced sleeping time by i.c.v. administration (5, 10 and 20 μg/mouse) in both sexes of mice. On the other hand, CBD did not show any significant prolongation by i.c.v. administration in male mice, although it prolonged the sleeping time in female mice by the same treatment. The result indicates that female mice are more sensitive to the sleep prolonging effect of the cannabinoids. 3) CBD showed an inhibitory effect on p-nitroanisole O-demethylase and aniline hydroxylase in vivo and in vitro. Δ⁹-THC also showed the inhibitory effect, but to lesser extents. 4) Kinetic analysis showed that CBD has lower K₁ values for p-nitroanisole O-demethylase and aniline hydroxylase than Δ⁹-THC in both sexes of mice. The inhibitory effect of the cannabinoids was more remarkable in male than in female. 5) The in vivo inhibitory effect of the cannabinoids was paralleled to the reduction of cytochrome P-450 content in hepatic microsomes. It is concluded that CBD has greater inhibitory effect on hepatic microsomal drug metabolizing enzymes of male and female mice than Δ⁹-THC.

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YAKUGAKU ZASSHI

YAKUGAKU ZASSHI 103 (12), 1289-1297, 1983

The Pharmaceutical Society of Japan

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Sex Difference in the Effects of Δ<SUP>9</SUP>-Tetrahydrocannabinol and Cannabidiol on Pentobarbital-Induced Sleeping Time and Hepatic Microsomal Drug Metabolizing Enzyme Systems in Mice