Molecular and structural insights into the 5‐HT_2C receptor as a therapeutic target for substance use disorders

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‐HT2C receptor) make it a candidate of interest for the treatment of SUD. Recently, psychedelics, which broadly act at 5‐HT2 receptors, have indicated potential for the treatment of SUD, implicating the 5‐HT2C receptor. The modern psychedelic movement has rekindled interest in the 5‐HT2C receptor, resulting in many new studies, especially structural analyses.This review explores the structural, molecular and cellular mechanisms governing 5‐HT2C 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.

A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics

“…Another receptor that may contribute to the therapeutic effects of psychedelics is the trace amine-associated receptor (TAAR), as psychedelics activate the TAAR1 receptor, subsequently exerting an inhibitory influence on dopaminergic activity [253,254].…”