Inhibition of methamphetamine self-administration in rats by cannabinoid receptor antagonist AM 251

Cannabinoids are drugs that are frequently abused not only alone, but also in combination with other drugs. The present study investigated possible functional interactions between the psychostimulant methamphetamine and the cannabinoid receptor agonists anandamide, or R-(+)-methanandamide and cannabinoid antagonist AM 251 in the rat model of i.v. drug self-administration. In rats trained to self-administer methamphetamine, the intake was significantly decreased by the cannabinoid antagonist and tended to be dose-dependently increased by pre-treatment with cannabinoid receptor agonists. Possible mechanisms for these drug interactions are discussed and the use of the cannabinoid antagonist for the treatment of drug abuse is considered.