Drugs that stimulate a specific cannabinoid receptor in the brain can counteract the behavioral and rewarding effects of cocaine in mice, reports a study online this week in Nature Neuroscience. This work suggests that the brain cannabinoid receptor may be a suitable target to mitigate drug abuse and addiction.

Cannabinoids are psychoactive compounds, found for example in marijuana, and their behavioural effects are mediated by the cannabinoid receptors CB1 and CB2. While drugs that activate the CB1 receptor are known to stimulate the brain’s reward system and provoke relapse to drug seeking after prolonged withdrawal, the role of brain CB2 receptors in modulating the effects of drug-of-abuse is not known.

Zheng-Xiong Xi and colleagues found two classes of drugs that selectively activate the CB2 receptors. When these drugs were given to mice just before they were allowed to self-administer cocaine, the team discovered that CB2 activation reduced the bouts and amount of drug intake, as well as the subsequent cocaine-induced locomotor-stimulating effects seen in the mice.