Effect of cannabidiol on cytochrome P-450 and hexobarbital sleep time

Abstract

The influences of acute and subacute cannabidiol (CBD) treatment and of subsequent drug withdrawal were investigated on hexobarbital-induced sleep time, on hepatic cytochrome P-450 concentration, on the in vitro formation of carbon monoxide (CO) associated with CBD metabolism, and on the kinetics of aminopyrine N-demethylase metabolism. In acutely treated mice, CBD prolonged sleep time, decreased cytochrome P-450 concentration, decreased the endogenous formation of CO, and increased an apparent K m for aminopyrine N-demethylase activity. In subacutely treated animals, tolerance developed to the effect on sleep time but not to that on cytochrome P-450 concentration nor on the endogenous formation of CO in vitro nor on the K m for the N-demethylase activity. Upon withdrawal from subacute treatment, tolerance to the sleep-time effect was still evident on day 14, but, by day 28, the sensitivity to CBD had returned to normal. In contrast, the cytochrome P-450 concentration returned to normal on day 14 of withdrawal, as did the K m for the N-demethylase activity and the ability of CBD to induce CO synthesis in vitro. The comparative results lead us to conclude that the CBD effect on sleep time does not correlate with either the total amount of cytochrome P-450 or with the CBD depressant effect on the cytochrome.