Perspectives in Pharmacology Cannabinoid CB1 Receptor Antagonists as Promising New Medications for Drug Dependence

This review examines the development of cannabinoid CB1 receptor antagonists as a new class of therapeutic agents for drug addiction. Abused drugs [alcohol, opiates, 9-tetrahydro-cannabinol (9-THC), and psychostimulants, including nicotine] elicit a variety of chronically relapsing disorders by interacting with endogenous neural pathways in the brain. In particular, they share the common property of activating mesolimbic do-pamine brain reward systems, and virtually all abused drugs elevate dopamine levels in the nucleus accumbens. Cannabi-noid CB1 receptors are expressed in this brain reward circuit and modulate the dopamine-releasing effects of 9-THC and nicotine. Rimonabant (SR141716), a CB1 receptor antagonist, blocks both the dopamine-releasing and discriminative and rewarding effects of 9-THC in animals. Blockade of CB1 re