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Getting to the core of addiction: Hooking CB2 receptor into drug abuse?

Nature Medicine volume 18, pages 504–505 (2012)Cite this article

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Despite considerable interest in developing effective medications and behavioral interventions to treat cocaine addiction, there is, unfortunately, no effective treatment. A recent study by Xi et al.1 sheds unexpected light on a potential new path toward developing antiaddiction therapies, showing that activation of brain cannabinoid type 2 (CB2) receptors attenuated both the rewarding and the psychomotor-stimulating effects of cocaine.

However, before we get into more detail, let's take a step back. The endocannabinoid system is composed of the cannabinoid receptors, CB1 and CB2, endogenous ligands (endocannabinoids) and proteins involved in endocannabinoid synthesis and inactivation2,3. Increasing evidence indicates that endocannabinoids mediate various forms of short- and long-term plasticity in brain regions involved in the etiology of drug addiction. CB1 receptors are highly expressed through the brain in diverse types of neurons4,5, where they regulate neurotransmitter release and synaptic strength. In contrast, several studies in vivo have shown that although CB2 receptors are not present in microglia in the healthy brain, they are induced by changes in the microenvironment, including neuroinflammatory conditions6.

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Figure 1: In the NAcc, CB2 receptors may be expressed by resident neurons (GABA medium spiny neurons (MSN), GABA parvalbumin neurons or cholinergic neurons) or by neurons that project to the NAcc (glutamatergic neurons from cortex or hippocampus or dopaminergic neurons from the ventral tegmental area (VTA)).

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Authors and Affiliations

  1. Marisela Morales and Antonello Bonci are in the Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA.,

    Marisela Morales & Antonello Bonci

  2. Antonello Bonci is also in the Department of Neurology, University of California–San Francisco, San Francisco, California, USA, and,

    Antonello Bonci

  3. at the Solomon H. Snyder Neuroscience Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,

    Antonello Bonci

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  1. Marisela Morales
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  2. Antonello Bonci
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Correspondence to Antonello Bonci.

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Morales, M., Bonci, A. Getting to the core of addiction: Hooking CB2 receptor into drug abuse?. Nat Med 18, 504–505 (2012). https://doi.org/10.1038/nm.2722

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