Abstract

Cannabidiol (CBD) is a known inhibitor of a number of hepatic drug metabolism reactions. Its pharmacokinetics in the liver were studied to determine the relationship between the amount of CBD in this organ and the effect on barbiturate sleep time, which has been shown by others to reflect an inhibition of drug metabolism. A methanol extract of liver was subjected to thin-layer chromatography which yielded three distinct fractions: CBD, the monohydroxylated metabolites and a relatively polar, unidentified fraction. The quantitative analysis of these fractions, as a function of time after drug administration, indicated that CBD is metabolized rapidly: the apparent half life is only about 52 min, which is approximately the same value obtained for the monohydroxylated metabolites; both of these fractions have virtually disappeared from the liver at 4 hr, at which time a significant effect on sleep time still persists. In contrast, the unidentified metabolite fraction contains a substantial amount of cannabinoid throughout the course of the effect on sleep time. These data suggest that the inhibition of hepatic drug metabolism is not caused by either CBD or one of its monohydroxylated metabolites; rather, the effect correlates with the persistence of more polar metabolites.

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