Semaglutide and Other GLP-1 Receptor Agonists as Potential Therapies for Addiction – Mechanisms, Evidence, and Clinical Implications
DOI:
https://doi.org/10.12775/JEHS.2025.86.66921Keywords
Semaglutide, GLP-1 receptor agonists, Substance use disorders, Alcohol use disorder, Novel pharmacotherapiesAbstract
Objective: The aim of this article is to review and analyse the current state of knowledge on the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, in the treatment of substance use disorders (SUD). The analysis focuses on evaluating their effects on reducing craving and substance intake, as well as their potential as novel therapeutic interventions targeting neurobiological mechanisms of addiction.
Material and methods: A systematic literature review was conducted using PubMed, Scopus, and Google Scholar. Preclinical rodent studies and clinical/observational human studies evaluating the effects of GLP-1 receptor agonists, including semaglutide, on substance intake, craving, and relapse were included. Studies assessing impacts on dopaminergic pathways, the HPA axis, and neuroinflammation were also considered.
Results: Preclinical and clinical evidence indicates that GLP-1 receptor agonists, including semaglutide, reduce alcohol and drug intake, limit binge-like behaviors, and decrease relapse risk. Mechanisms likely involve modulation of dopaminergic pathways, regulation of the HPA axis, and reduction of neuroinflammatory processes. Clinical studies show decreased substance craving, lower consumption, and reduced relapse, with a favorable safety and tolerability profile. Observational real-world data further support effectiveness across different patient populations and substances.
Conclusions: GLP-1 receptor agonists, represent a promising novel pharmacotherapeutic approach for AUD and potentially other SUDs. Despite encouraging results, larger, multi-center trials with longer follow-up are necessary to establish definitive efficacy, safety, and optimal dosing strategies.
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