GLP-1 RECEPTOR AGONISTS AS EMERGING THERAPEUTICS FOR SUBSTANCE USE DISORDERS: A REVIEW OF MECHANISMS, EFFICACY, AND PUBLIC HEALTH IMPLICATIONS
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.5071Keywords:
GLP-1 Receptor Agonists, Semaglutide, Tirzepatide, Mesolimbic Dopamine System, Alcohol Use Disorder, Social Determinants of Health, Incentive SalienceAbstract
The convergence of the global obesity epidemic and the rising prevalence of substance use disorders (SUDs) presents a critical public health challenge that traditional therapeutic models have failed to address adequately. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatments for type 2 diabetes and obesity, recent data indicate they possess profound off-target effects on the central nervous system reward circuitry. This comprehensive narrative review synthesizes evidence published between 2023 and early 2026 to elucidate the neurobiological mechanisms and clinical efficacy of agents like semaglutide and tirzepatide in attenuating addictive behaviours. Through a systematic search of major biomedical databases, we analyse high-quality randomized controlled trials and retrospective cohort studies. The reviewed neurobiological data suggest that these agents modulate synaptic plasticity within the ventral tegmental area and nucleus accumbens to dampen phasic dopamine release. This mechanism effectively reduces the incentive salience of stimuli such as alcohol and opioids without inducing global anhedonia. Clinical evidence supports these findings by demonstrating significant reductions in alcohol intake, opioid overdose risk, and compulsive behavioural patterns. We conclude that while these pharmacotherapies offer a paradigm-shifting therapeutic potential for addiction, their integration into psychiatric practice requires a rigorous re-evaluation of access disparities and the bioethical implications of medicalizing consumption behaviours.
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Copyright (c) 2026 Natalia Bylak, Sebastian Konecki, Grzegorz Jałoszyński, Norbert Gromadzki, Anna Gwizdek, Marcin Patryk Barbachowski, Maciej Makarewicz, Maria Kurt, Dawid Szczepański, Bruno Makowski, Oliwia Marciniak
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