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Marijuana and cannabinoid regulation of brain reward circuits.

Carl R. Lupica, Arthur C Riegel, Alexander F. Hoffman

British Journal of Pharmacology September 2004 DOI: 10.1038/sj.bjp.0705931 (opens in new tab)

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Characteristics Review Peer reviewed
Topics Cannabis
Key findings The authors conclude that Delta(9)-THC alters the activity of central reward pathways in a manner consistent with other abused drugs, but the cellular mechanism is likely different, relying on combined regulation of several afferent pathways to the VTA. They propose that CB1 receptor activation within central brain reward circuits sustains marijuana self-administration and mediates its anxiolytic and pleasurable effects.

Abstract

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

Comparable studies

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Study Year Design Participants
Causal association between cannabis and psychosis: examination of the evidence 2004 Review
Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. General (historical and pharmacological review) 2018 Review
Psychiatric effects of cannabis 2001 Review
Beyond THC: The New Generation of Cannabinoid Designer Drugs 2011 Review
Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug 2006 Review

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