Molecular and structural insights into the 5‐HT2C receptor as a therapeutic target for substance use disorders

Substance use disorder (SUD) is a chronic condition marked by maintained substance abuse leading to physiological and psychological changes, often altering cognitive and social behaviors. Current therapies combining psychotherapy and medication have high relapse rates, revealing their limitations. The serotonin 2C receptor (5-HT2C receptor) is a candidate for SUD treatment due to its signaling, expression profile, and neurological function. Recent interest in psychedelics, which broadly act at 5-HT2 receptors, has rekindled studies on the 5-HT2C receptor, especially structural analyses. This review examines the structural, molecular, and cellular mechanisms governing 5-HT2C receptor function in SUD, summarizing preclinical and clinical evidence and highlighting future research potential.

Study at a glance

Abstract

Abstract 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.