Studies on the effects of Δ1-tetrahydrocannabinol (Δ1-THC) and DDT on the hepatic microsomal metabolism of Δ1-THC and other compounds in the rat

In view of the observations in man that chronic marihuana smokers exhibit a reduction in the half-life of administered radioactively labeled tetrahydrocannabinol (Δ1-THC), the possibility that exposure to marihuana stimulates the hepatic metabolism of Δ1-THC was considered. Thus, the effects of Δ1-THC or of a marihuana extract, containing 25% Δ1-THC, on the hepatic microsomal monooxygenase system in rats were examined. In addition, for comparison purposes, the effect of technical grade DDT on this enzyme system was also studied. The intraperitoneal administration of Δ1-THC for 3–9 days or the oral administration of Δ1-THC for 3 days did not affect the activity of the in vitro microsomal demethylation of aminopyrine and p-chloro-N-methylaniline (PCMA) or the oxidative metabolism of [ 14 C ]Δ 1 - THC (determined as residual Δ1-THC or as metabolite-7-hydroxy-Δ1-THC). Similarly the oral administration of a whole marihuana extract for 7 days did not affect the in vitro demethylation of aminopyrine or the hydroxylation of Δ1-THC. On the other hand, intraperitoneal injections of DDT for 3 days increased about two-fold the oxidative metabolism of Δ1-THC, demonstrating that the microsomal oxidation of Δ1-THC can be enhanced by an inducer of the monooxygenase system.