Cannabinoid CB1 receptor antagonists as potential pharmacotherapies for drug abuse disorders

Since the discovery of the cannabinoid CB1 receptor (CB1R) in 1988, and subsequently of the CB2 receptor (CB2R) in 1993, there has been an exponential growth of research investigating the functions of the endocannabinoid system. The roles of CB1Rs have been of particular interest to psychiatry because of their selective presence within the CNS and because of their association with brain-reward circuits involving mesocorticolimbic dopamine systems. One potential role that has become of considerable focus is the ability of CB1Rs to modulate the effects of the drugs of abuse. Many drugs of abuse elevate dopamine levels, and the ability of CB1R antagonists or inverse agonists to modulate these elevations has suggested their potential application as pharmacotherapies for treating drug abuse disorders. With the identification of the selective CB1R antagonist, rimonabant, in 1994, and subsequently of other CB1R antagonists, there has been a rapid expansion of research investigating their ability to modulate the effects of the drugs of abuse. This review highlights some of the preclinical and clinical studies that have examined the effects of CB1R antagonists under conditions potentially predictive of their therapeutic efficacy as treatments for drug abuse disorders.