Metabolic interactions of phencyclidine (PCP) and delta 9-tetrahydrocannabinol (THC) in the rat

The in vitro effects of THC on the metabolism of PCP by rat liver were determined. Samples containing 1 mM PCP were incubated for 1 hr at 37 degrees C with an NADPH-generating system containing 10,000 X g supernatant or Ca++-precipitated rat liver microsomes. These incubations were carried out in the presence or absence of THC and at the end of 1 hr, PCP metabolites were determined by gas chromatography. In the presence of 0.1, 0.05, 0.025 and 0.0125 mM THC, the production of 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (metabolite I) by the 10,000 X g supernatant was decreased by 46, 29, 23 and 16% respectively. Similarly, production of 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (metabolite II) was reduced significantly by 58, 44, 34 and 23% with the respective concentrations of THC. However, the production of 1-phenylcyclohexylamine (metabolite III) was increased by 18, 32, 30 and 22% with 0.1, 0.05, 0.025 and 0.0125 mM THC. Incubations with Ca++-precipitated liver microsomes revealed similar trends in PCP metabolism in the presence or absence of THC. Metabolites I and II were reduced by 62 and 67% by 0.1 mM THC. Another concentration of THC (0.025 mM) caused a 50 and 62% decrease in I and II. These observations suggest that THC alters the in vitro microsomal metabolism of PCP.