The overall objective of the proposed research is to characterize the effects of cannabinoids on complex, discrimination tasks involving learning and memory in nonhuman primates. A repeated acquisition and delayed performance procedure will be used to assess the effects of cannabinoids on memory in monkeys. These studies will enhance our understanding of how the cannabinoids affect complex behavioral processes and cognition. The first series of proposed studies are specifically aimed at continuing and extending our studies of the effects of various cannabinoid agonists and antagonists on the acquisition and performance of discriminations in monkeys. Specifically, acute dose-effect curves for the agonists 69-THC, CP55,940, cannabidiol, and R-methanandamide and the antagonist SR141716A will be determined. Each agonist will then be tested in combination with BR141716A in order to characterize the nature of the antagonism. These studies are designed to test the hypothesis that the cannabinoid receptor system plays a role in modulating cognitive processes involved in learning. The second series of studies will characterize the acute effects of these same cannabinoid agonists on memory in monkeys. Specifically, these studies will evaluate the amnestic effects of these drugs and their actions on storage and retrieval processes following both short and long delays. These studies are designed to test the hypothesis that the cannabinoid receptor system plays a role in modulating cognitive processes involved in memory. Because polydrug abuse continues to be a major health-care problem, the third series of studies involves the acute characterization of cannabinoids in combination with other prototypical drugs of abuse. Specifically, cannabinoid ligands will be investigated in combination with opioids (heroin, methadone & buprenorphine), stimulants (cocaine, amphetamine & nicotine), and sedative-hypnotics (lorazepam 8 pentobarbital). These studies are designed to test the hypothesis that the effects of the cannabinoids on learning and memory are potentiated by other drugs of abuse. Together these studies will provide new information that will be of direct relevance to the clinical management of the cannabinoid user. In addition, studies involving the actions of the cannabinoid receptor antagonist alone will provide valuable data concerning the potential use of this and related agents in the pharmacotherapy of cannabinoid abuse.
