The metabolism and excretion of Δ9-tetrahydrocannabinol in the rat

Abstract

THE AVAILABILITY of synthetic Δ 9-tetrahydrocannabinol (THC), a psychotomimetic component of marihuana has stimulated the investigation of its behavioral effects and pharmacological actions. Recent reports have described the excretion of THC (1,2), the formation of the 11-hydroxy metabolite of THC by liver microsomes (3,4) and its excretion in urine (5). The present studies were undertaken to further investigate the fundamental aspects of the fate of THC in rats. These studies have confirmed the findings of Agurell et al , that in rats THC is excreted almost completely in feces as more polar metabolites. Moreover, evidence is presented which shows that THC disappears from the tissues of rats in a biphasic fashion. That is, immediately after its administration the levels of THC in rats decline very rapidly; after several hours, however, the compound disappears with a long half-life which resembles the rate of excretion of metabolites in urine and feces. Moreover, it appears that neither the hepatic metabolism nor excretion in bile are limiting factors in the excretion of metabolites of THC in feces. The rate of excretion of these compounds is probably determined by their rate of movement down the intestine possibly combined with an enterohepatic circulation.