Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder
Open accessAbstract
Cocaine use disorder (CUD) is a major public health challenge with a high relapse rate and lack of effective pharmacotherapies; therefore, there is a substantial need to identify novel medications to treat this epidemic. Since the advent of glucagon-like peptide-1 (GLP-1) receptors (GLP-1Rs) agonists (GLP-1RAs), their potential has been extensively explored and expanded. In this review, we first summarized the biological effects of GLP-1, GLP-1Rs, and GLP-1RAs. Subsequently, the recent literature examining the behavioral effects and the possible pharmacological mechanisms of GLP-1RAs on CUD was reviewed. Increasing preclinical evidence suggests that GLP-1RAs are promising in regulating dopamine release, dopamine transporter (DAT) surface expression and function, mesolimbic reward system and GABAergic neurons, and maladaptive behaviors in animal models of self-administration and conditioned place preference. In addition, the emerging role of GLP-1RAs in inhibiting inflammatory cytokines was reported. These findings indicate that GLP-1RAs perform essential functions in the modulation of cocaine-seeking and cocaine-taking behaviors likely through multifaceted mechanisms. Although the current preclinical evidence provides convincing evidence to support GLP-1RA as a promising pharmacotherapy for CUD, other questions concerning clinical availability, impact and specific mechanisms remain to be addressed in further studies.
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Users' alterations in alcohol consumption and substance use following initiation of semaglutide 2.4 mg contribute to existing literature supporting GLP-1RA as a potential treatment approach for addiction.
“Users have also noted alterations in alcohol consumption and substance use following the initiation of semaglutide 2.4 mg, contributing to the existing body of literature supporting GLP‐1RA as a potential treatment approach for addiction [21, 23, 26, 27].”
From A Qualitative Analysis of Patient Experiences Using Semaglutide 2.4 mg for Weight Loss (2025) · cites this paper as [27]
The Conclusion describes GLP-1RAs as promising potential treatments for cocaine use disorder, supporting the sentence’s broader addiction-treatment rationale. It does not report users’ changes in alcohol consumption or substance use after starting semaglutide 2.4 mg; the Conclusion also says the promising addiction findings are largely preclinical. (LLM, conf=0.87)
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- Authors
- Zhu, C., Li, H., Kong, X., Wang, Y., Sun, T., & Wang, F.
- Affiliations
- Ningxia Medical University (CN)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Corresponding author
- Wang, Yezhong
- Sun, Tao
- Wang, Feng
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2022-03-01
- Volume
- 13
- Pages
- 819470-819470
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC8921771
- OpenAlex
- W4214722065
- Cited by
- 26
- References
- 117
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 9 · 2023: 2 · 2022: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82060261, 81660226, 2018BFG02007)
- Ningxia Medical University
- Key Research and Development Program of Ningxia (2018BFG02007)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- cocaine dependence, GLP-1 receptor agonists, GLP-1 receptor, dopamine release, dopamine transporter, mesolimbic reward system, GABAergic neurons, cocaine self-administration, conditioned place preference, cocaine-seeking behavior, inflammatory cytokines, pharmacotherapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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