Glucagon-Like Peptide-1 Receptor Agonists in Cocaine Use Disorder: Clinical Observations and Underlying Mechanisms.

Authors

Céline Eiden, Ghjulia Chautard, Anne Batisse, Aurélie Aquizerate, Amandine Luquiens, Hélène Donnadieu, Jean-Luc Faillie, Hélène Peyriere

Published in

Fundamental & clinical pharmacology. Volume 40. Issue 4. Pages e70103.

Abstract

Cocaine use disorder (CUD) remains a major public health concern, characterized by high relapse rates and the absence of approved pharmacological treatments. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for metabolic disorders, modulate mesolimbic reward pathways and have been proposed as potential modulators of addictive behaviors.
To describe clinical observations of GLP-1RA exposure in individuals with CUD identified through the French national vigilance system and to contextualize these findings through a structured narrative review of preclinical and clinical evidence.
Cases involving GLP-1RA exposure in individuals with ongoing cocaine use were identified through the French national vigilance system and described. A structured literature search (MEDLINE, Embase, Google Scholar) identified original preclinical and clinical studies examining the effects of GLP-1 receptor activation on cocaine-related behavioral and neurobiological outcomes.
Two cases involving patient-initiated off-label GLP-1RA use motivated by perceived anti-craving effects were identified through the vigilance system. The literature synthesis included 22 original publications (17 preclinical and 5 human studies). Across experimental models, GLP-1 receptor activation reduced cocaine self-administration, conditioned reward, and relapse-like behaviors. These effects were associated with the attenuation of mesolimbic dopamine signaling, including reduced cocaine-evoked dopamine release and modulation of dopamine transporter function. Human evidence remains limited and heterogeneous.
GLP-1 receptor signaling represents a biologically plausible target in CUD. However, current clinical evidence remains preliminary. Patient-driven observations underscore the need for controlled clinical trials and continued vigilance monitoring.

PMID:
42380081
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.

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