Glucagon‐Like Peptide‐1 Receptor Agonists in Cocaine Use Disorder: Clinical Observations and Underlying Mechanisms
Céline Eiden, Ghjulia Chautard, Anne Batisse, Aurélie Aquizerate, Amandine Luquiens, Hélène Donnadieu, Jean‐Luc Faillie, Hélène PeyriereABSTRACT
Background
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.
Objectives
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.
Methods
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.
Results
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.
Conclusion
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