CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL METABOLISM - INVITRO COMPARISON OF MOUSE AND RAT-LIVER CRUDE MICROSOME PREPARATIONS

The in vitro biotransformations of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ-THC) by hepatic microsomal preparations from mouse and rat were compared and it was found that both cannabinoids are metabolized approximately two to three times faster by a mouse preparation than by a similar preparation from the rat. In both species, however, CBD was metabolized more slowly than Δ9-THC. The metabolite patterns resulting from the biotransformations of radioactive CBD and Δ9-THC were examined by thin-layer chromatography and were found to be qualitatively identical in both the mouse and rat. In contrast, studies of the rate of cannabinoid metabolism in the presence of excess substrate revealed that CBD metabolism was only linear for about 10 min, whereas Δ9-THC metabolism was linear for about 60 min. This difference was noted in both species. The evidence suggests that CBD metabolism is inhibited by its own metabolites. Furthermore, the results of other experiments indicate that CBD metabolites can also inhibit Δ9-THC and aminopyrine metabolism. The established ability of CBD to inhibit hepatic microsomal drug metabolism in vivo may also be the consequence of the formation of inhibitory metabolites. © 1979.