Semaglutide and Drug Craving: Emerging Perspectives in Addiction Psychiatry

Abstract

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist used for type 2 diabetes and obesity, has attracted interest as a potential modulator of drug craving and substance-related reinforcement. This mini-review examines mechanistic and clinical evidence across cocaine, alcohol, nicotine, and opioid use disorders. Preclinical studies implicate mesolimbic GLP-1 signalling in reward, cue reactivity, and consummatory behaviour. Human evidence remains limited but is most persuasive for alcohol use disorder, where randomized subcutaneous and oral semaglutide trials have reported improvements in selected drinking and craving outcomes; evidence for cocaine and nicotine remains preliminary or mixed, and opioid evidence is largely observational or protocol-level. A central interpretative challenge is whether apparent benefits reflect direct reward modulation or indirect effects of appetite suppression, gastrointestinal symptoms, weight loss, or metabolic improvement. Semaglutide is not an established pharmacotherapy for substance use disorders, and approved metabolic indications must remain distinct from investigational anti-craving use. Further trials should use substance-specific clinical outcomes, objective measures of consumption, formal mediation analyses, representative psychiatric populations, and longer follow-up.