Abstract: Substance Use Disorders (SUDs) involving alcohol, nicotine, and opioids constitute a substantial global health burden, with current pharmacotherapies often limited by efficacy issues or adverse effects. This review examines the emerging therapeutic potential of Glucagon-Like Peptide-1 (GLP-1) receptor agonists, specifically Semaglutide, in modulating reward circuitry. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science for studies published between 2018 and 2024. Preclinical findings indicate that Semaglutide significantly attenuates the intake of alcohol, opioids, and nicotine in rodent models by suppressing dopamine release in the nucleus accumbens and enhancing GABAergic transmission. Clinical observations from metabolic disorder treatments suggest a concurrent reduction in substance cravings. The underlying mechanisms appear to involve the restoration of blood-brain barrier integrity, reduction of neuroinflammation, and direct modulation of the mesolimbic reward system. These findings suggest Semaglutide possesses significant neuroprotective and anti-craving properties, warranting further investigation through large-scale randomized controlled trials.

Keywords: Semaglutide, GLP-1 Receptor Agonists, Substance Use Disorders, Neuroprotection, Addiction, Reward Circuitry.

Downloads: | DOI: 10.17148/IARJSET.2026.13142