Borys H K, Ingall G B, Karler R
Br J Pharmacol. 1979 Sep;67(1):93-101.
1 The effects of acute and subacute cannabidiol (CBD) administration on hexobarbitone sleeping time and on some constituents of the hepatic microsomal drug-metabolizing system were assessed in the mouse.2 Acutely administered CBD prolonged sleeping time; but with subacute treatment, tolerance to the effect rapidly developed.3 Brain hexobarbitone concentration upon awakening was unchanged by either acute or subacute CBD treatment, which suggests that neither the prolongation of sleeping time nor the tolerance is the result of a change in sensitivity of the central nervous system to the barbiturate.4 Acute CBD treatment increased the half-time of hexobarbitone in the brain, which returned toward normal with the development of tolerance.5 Acutely, CBD caused a 30% decrease in hepatic cytochrome P-450 level; with tolerance, the cytochrome concentration returned to normal.6 The evidence suggests that the CBD-induced prolongation of barbiturate sleeping time and the tolerance to this effect are the result of changes in the rate of drug metabolism, which are related to changes in the amount of cytochrome P-450.7 The effects of CBD on the hepatic microsomal drug-metabolizing enzyme system are different from those attributed to SKF 525-A and piperonyl butoxide because the cannabinoid does not decrease cytochrome P-450 quantitatively by complex formation, it does not produce a recovery overshoot in the cytochrome concentration and, finally, it does not cause an induction of the hexobarbitone-metabolizing enzymes.
在小鼠中评估了急性和亚急性给予大麻二酚（CBD）对己巴比妥睡眠时间以及肝微粒体药物代谢系统某些成分的影响。
急性给予CBD可延长睡眠时间；但在亚急性治疗时，对该作用的耐受性迅速产生。
急性或亚急性CBD治疗后，觉醒时脑内己巴比妥浓度均未改变，这表明睡眠时间的延长和耐受性均不是中枢神经系统对巴比妥类药物敏感性改变的结果。
急性CBD治疗增加了脑内己巴比妥的半衰期，随着耐受性的产生，半衰期恢复正常。
急性时，CBD使肝细胞色素P - 450水平降低30%；随着耐受性的产生，细胞色素浓度恢复正常。
证据表明，CBD诱导的巴比妥类睡眠时间延长及对此作用的耐受性是药物代谢速率变化的结果，这与细胞色素P - 450量的变化有关。
CBD对肝微粒体药物代谢酶系统的作用不同于SKF 525 - A和胡椒基丁醚，因为大麻素不会通过形成复合物定量降低细胞色素P - 450，不会在细胞色素浓度上产生恢复超调，并且最终不会诱导己巴比妥代谢酶。
