The widespread use of cocaine (COC) in recent years has been accompanied by a corresponding increase in the use of drugs such as marihuana, phencyclidine (PCP), amphetamines, methaqualones and others. This increase in polydrug abuse has resulted in a number of clinical dilemmas, the recognition and management of which has constantly challenged the medical community. Although much is known about the pharmacology of these agents, it is not known whether the behavioral and biochemical changes observed in these patients are a consequence of dispositional and/or metabolic interactions between these drugs. Therefore, the long tens goals of this proposal are to elucidate the mechanisms of dispositional and/or metabolic interactions involving COC, PCP and three major constituents of marihuana, delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). Six types of studies will be conducted in rats to characterize the effects of acute and chronic THC treatment on the following pharmacologic properties of COC and PCP: plasma pharmacokinetic profiles; distribution in brain, liver, lung, kidney, testis, and adipose tissue; urinary, biliary and fecal excretion; changes in metabolism; plasma protein binding; and toxicity (ED50, LD50). Comparisons will be made in these various studies between groups treated with COC or PCP alone or in combination with THC, CBD and CBN. Methods utilized in these studies will include different radioisotope techniques, extraction and purification procedures, and thin layer chromatography. The results of the proposed studies should help identify some of the other mechanisms besides dopaminergic pathways for the drug interactions involving COC. PCP and the cannabinoids. This information will not only enlarge our basic knowledge about the pharmacology of these agents, but should also aid in the identification and development of different treatment strategies for the unsuspected interactions resulting from the concurrent abuse of these drugs.
| Husain, S; Ahmed, K M (1991) Tissue glutathione levels in mice treated with delta-9-tetrahydrocannabinol. Pharmacol Biochem Behav 40:513-5 |
| Husain, S; Anwer, J (1991) Characteristics of cocaine interaction with delta-9-tetrahydrocannabinol on glucose metabolism in the rat testis. Pharmacol Biochem Behav 40:625-8 |
| Husain, S (1989) Energy substrate metabolism in testis of rats treated with delta-9-tetrahydrocannabinol (THC) and cocaine (COC). NIDA Res Monogr 95:509-10 |
