Gregory D. Stewart

Substance use disorder (SUD) is a chronic condition, with maintained abuse of a substance leading to physiological and psychological alterations and often changes in cognitive and social behaviours. Current therapies include psychotherapy coupled with medication; however, high relapse rates reveal the shortcomings of these therapies. The signalling, expression profile, and neurological function of the serotonin 2C receptor (5‐HT 2C receptor) make it a candidate of interest for the treatment of SUD. Recently, psychedelics, which broadly act at 5‐HT 2 receptors, have indicated potential for the treatment of SUD, implicating the 5‐HT 2C receptor. The modern psychedelic movement has rekindled interest in the 5‐HT 2C receptor, resulting in many new studies, especially structural analyses. This review explores the structural, molecular and cellular mechanisms governing 5‐HT 2C receptor function in the context of SUD. This provides the basis of the preclinical and clinical evidence for their role in SUD and highlights the potential for future exploration.