GLP-1 receptor agonists, dopamine D3 receptor antagonists, and CRF antagonists each target different aspects of addiction and show preclinical promise for treating alcohol, opioid, and stimulant use disorders.
3 mechanisms, 1 goalGLP-1 receptor agonists modulate reward, D3R antagonists reduce drug-seeking, and CRF antagonists prevent stress-driven relapse — together offering a multi-pronged approach to treating substance use disorders.
What the researchers found
This review examines three emerging therapeutic classes for substance use disorders: GLP-1 receptor agonists, dopamine D3 receptor antagonists, and corticotropin-releasing factor (CRF) antagonists. GLP-1 receptor agonists (like semaglutide and liraglutide) show promise in reducing alcohol and substance use by modulating the brain's reward circuitry — preclinical studies demonstrate reduced drug-seeking behavior, and early clinical observations are encouraging. CRF antagonists target the stress and relapse pathways, while D3R antagonists specifically modulate reward processing. Together, these three approaches address different stages and mechanisms of addiction: reward, stress, and relapse.
Why it matters
Substance use disorders affect hundreds of millions of people globally and current treatments are inadequate — approved medications exist for only a few substances (alcohol, opioids, nicotine), often with limited efficacy and significant side effects. The discovery that GLP-1 receptor agonists — drugs already widely prescribed for diabetes and obesity — may also reduce addictive behaviors opens a potentially game-changing treatment avenue. Combined with CRF and D3R-targeting approaches, a multi-pronged pharmacological strategy for addiction is emerging.
The numbers in context
3 therapeutic classes reviewed · Targets: alcohol, opioid, and stimulant use disorders · GLP-1 RAs, D3R antagonists, CRF antagonists
How the study worked
This is a narrative review of preclinical and clinical literature on three emerging therapeutic classes for substance use disorders. The authors examine evidence from animal models of addiction and available human studies for GLP-1 receptor agonists, dopamine D3 receptor antagonists, and corticotropin-releasing factor antagonists.
Who was studied
Not applicable — review covering preclinical and clinical studies on substance use disorders involving alcohol, opioids, and stimulants
What this study cannot tell us
Most evidence for these therapies comes from preclinical animal studies, with limited clinical trial data available. The review does not perform systematic search or meta-analysis. GLP-1 agonist effects on addiction are largely observational in humans (e.g., noticed in patients taking the drugs for other reasons), not from dedicated addiction trials. CRF antagonists have historically had disappointing clinical results despite strong preclinical data. The optimal doses, treatment durations, and patient populations for addiction applications remain undefined.
How to read the evidence
This is a narrative review covering a mix of preclinical and early clinical evidence. Most findings come from animal models, with human evidence for GLP-1 agonists primarily observational. No large randomized controlled trials have been completed for any of these agents specifically for addiction.
When this study was published
Published in 2025, this review captures a moment of intense interest in repurposing GLP-1 agonists for addiction — a hypothesis that has gone from anecdotal observation to active clinical investigation in just a few years. The field is evolving rapidly.
The bigger picture
The observation that patients taking GLP-1 drugs for diabetes or obesity spontaneously reduced their alcohol and substance use has generated enormous excitement in addiction medicine. This review places GLP-1 agonists alongside two other promising classes to frame a comprehensive pharmacological strategy for addiction that addresses reward (D3R), stress/relapse (CRF), and broader mesolimbic modulation (GLP-1). If any of these approaches proves effective in clinical trials, it could represent the first new addiction medication breakthrough in decades.
Questions still open
- Will dedicated clinical trials of GLP-1 receptor agonists for addiction confirm the promising signals from preclinical studies and clinical observations?
- Could combining these three therapeutic approaches (GLP-1 agonists + D3R antagonists + CRF antagonists) be more effective than any single agent?
- Why have CRF antagonists underperformed in clinical addiction trials despite strong preclinical evidence, and can this translational gap be bridged?
Common questions
Can Ozempic or Wegovy treat addiction?
Why do we need new addiction medications?
Read the original research
Emerging Therapeutics in the Treatment of Substance Use Disorders: A Focus on GLP-1 Receptor Agonists, D3R Antagonists, and CRF Antagonists.
Journal of integrative neuroscience, 24(4), 26361
Citation
Draghmeh, Khaled; Fuehrlein, Brian. (2025). Emerging Therapeutics in the Treatment of Substance Use Disorders: A Focus on GLP-1 Receptor Agonists, D3R Antagonists, and CRF Antagonists.. Journal of integrative neuroscience, 24(4), 26361. https://doi.org/10.31083/JIN26361