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2000
Volume 23, Issue 8
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190
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Abstract

Introduction

Glucagon-Like Peptide-1 Receptor (GLP1R) agonists have become widespread anti-obesity/diabetes pharmaceuticals in the United States.

Aim

This article aimed to provide our current knowledge on the plausible mechanisms linked to the role of Ozempic (Semaglutide), which is generalized as one of the anti-addiction compounds.

Methods

The effects of GLP1R agonists in Alcohol Use Disorder (AUD) and substance use disorder (SUD) are mediated, in part, through the downregulation of dopamine signaling. We posit that while GLP1R agonism could offer therapeutic advantages in hyperdopaminergia, it may be detrimental in patients with hypodopaminergia, potentially leading to long-term induction of Suicidal Ideation (SI). The alleged posit of GLP1 agonists to induce dopamine homeostasis is incorrect. This study refined 31 genes based on the targets of Ozempic, , and related enzymes for SI and 10 genes of the Genetic Addiction Risk Score (GARS) test. STRING-MODEL refined 29 genes, and further primary analyses indicated associations of with , , , , and .

Results

In-depth silico enrichment analysis revealed an association between candidate genes and depressive phenotypes linked with dopaminergic signaling. Finally, through primary and in-depth silico analyses, we demonstrated multiple findings supporting that GLP1R agonists can induce depression phenotypes.

Conclusion

Our findings suggest that associated polymorphisms seem to have overlapping effects with addictive behaviors of Reward Deficiency Syndrome (RDS) and dopamine regulation. Consequently, GLP1R agonists may represent a double-edged sword, potentially triggering both anti-addictive effects and SI by exacerbating depressive phenotypes. Thus, we encourage the scientific community to perform further empirical clinical studies to confirm this proposed pathway.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and the Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicidal Ideation and Substance Use Disorder
Curr. Neuropharmacol. 23, 974 (2025); https://doi.org/10.2174/011570159X349579241231080602
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  • Article Type:     Research Article
Keyword(s): dopamine homeostasis; GLP1; in-depth in silico; Ozempic; substance use disorder; suicide ideation

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