GLP-1 receptor agonists at the crossroads of obesity and addiction: A review of shared neurobiology and translational evidence.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and pilot trials without systematic meta-analysis
PubMed 42184906 · doi:10.1016/j.pbb.2026.174217
What was done
This narrative review synthesized translational evidence and shared neurobiological mechanisms between obesity and substance use disorders (SUDs) regarding glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The authors searched PubMed/MEDLINE, Embase, PsycINFO, and Web of Science from January 2015 through December 2025, along with manual reference screening, to identify eligible preclinical studies and pilot clinical trials evaluating GLP-1 RAs in substance-related behaviors.
What was found
The abstract reports no numerical data, pooled estimates, or effect sizes. Preclinical findings showed that GLP-1 RAs reduced intake and seeking across alcohol, nicotine, opioids, and psychostimulants via mesolimbic dopamine signaling modulation. Early pilot clinical trials demonstrated therapeutic promise for reducing alcohol use, aiding smoking cessation, and limiting post-cessation weight gain.
Why it matters
GLP-1 RAs represent a promising repurposing strategy for substance use disorders that share reward circuitry dysregulation with obesity, offering a potential dual-target intervention for patients with comorbid conditions.
Limits
As a narrative review, it lacks quantitative meta-analytic pooling. The underlying human clinical literature is restricted to pilot trials with modest sample sizes and short follow-up durations; clinical efficacy and optimal dosing remain unestablished for opioid and psychostimulant use disorders.
Cited by
- supports GLP-1 receptor agonists reduce desire in reward pathways, with emerging evidence showing decreased cravings for addictive behaviors such as gambling, shopping, alcohol, and smoking.