The medications transforming diabetes and weight loss treatment might have an unexpected side effect: reducing cravings for alcohol, opioids, and cigarettes. A new review published in the Journal of the Endocrine Society examines how GLP-1 receptor agonists, the drug class that includes Ozempic and Wegovy, could represent a promising approach to treating substance use disorders, conditions that claimed millions of lives last year while existing treatments reached only a fraction of those who needed help.
The connection isn’t entirely surprising. Researchers have long noticed overlapping brain circuits between addiction and compulsive eating, particularly in regions like the ventral tegmental area and nucleus accumbens that process reward. Some forms of obesity show biochemical signatures remarkably similar to addiction, though drawing that parallel remains controversial. What’s less debatable is that pathways involved in substance cravings also drive pathological overeating.
Early research in both animals and humans suggests that these treatments may help reduce alcohol and other substance use. Some small clinical trials have also shown encouraging results.
That quote comes from Lorenzo Leggio, a researcher at the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, who led the review. The paper synthesizes evidence from rodent studies, electronic health records, and the handful of human trials completed so far. In mice and rats, various GLP-1 drugs reduced self-administration of heroin, fentanyl, oxycodone, cocaine, and nicotine. They also decreased the reinstatement of drug-seeking behavior—the animal model equivalent of relapse.
From Lab Bench to Clinic
The human data, while preliminary, follows a similar pattern. One randomized trial found that low-dose semaglutide reduced laboratory alcohol consumption in people with alcohol use disorder. It also lowered drinks per drinking day and subjective cravings. Denmark’s national health records showed reduced risk of alcohol-related events among patients prescribed GLP-1 drugs. Another trial found exenatide, an earlier GLP-1 medication, helped with smoking cessation and prevented the weight gain that typically derails quit attempts.
The mechanism appears to involve multiple systems. GLP-1 receptors populate not just the pancreas and gut, but brain regions controlling appetite, reward, and impulse control. When activated, they modulate dopamine signaling in ways that seem to dampen both the appeal of drugs and the drive to seek them out. The effect extends to the prefrontal cortex, which governs executive function and decision-making—capabilities often impaired in addiction.
Current addiction treatments leave much to be desired. Fewer than 25 percent of people with substance use disorders received treatment in 2023, and less than 2 percent of those with alcohol problems got medication. Stigma explains part of that gap, but so does the limited menu of approved drugs. For alcohol dependence, doctors can prescribe disulfiram, acamprosate, or naltrexone. Opioid addiction has methadone, buprenorphine, and naltrexone. Tobacco treatment includes nicotine replacement, varenicline, and bupropion. Cannabis and stimulant addictions have no approved medications at all.
Complications and Questions
GLP-1 drugs bring their own complications. Nausea tops the list of side effects, followed by vomiting, diarrhea, and constipation. Long-term use may affect muscle mass, a concern for patients with addiction who often have nutritional deficiencies. Some people regain weight after stopping the drugs, and most patients discontinue within a year due to side effects, cost, or plateauing results. Whether similar patterns would emerge in addiction treatment remains unknown.
The review acknowledges these uncertainties while noting the stakes involved. Alcohol alone caused 2.6 million deaths globally in 2019. Opioid overdoses continue climbing. Meanwhile, the neurobiological overlap between addiction and metabolic disorders keeps drawing researchers back to GLP-1 drugs as a potential solution. Naltrexone already bridges both worlds—it treats alcohol and opioid dependence while also appearing in the combination drug for obesity.
This research is very important because alcohol and drug addiction are major causes of illness and death, yet there are still only a few effective treatment options. Finding new and better treatments is critically important to help people live healthier lives.
Several clinical trials are now underway testing GLP-1 drugs and newer multi-receptor agonists in people with alcohol, opioid, cocaine, and tobacco addictions. Some studies focus on patients with comorbid conditions like liver disease or schizophrenia. The results won’t arrive for years, leaving patients and doctors to weigh anecdotal reports against the absence of rigorous evidence. Social media fills with stories of reduced drinking or smoking after starting these medications, but such accounts can’t replace controlled trials.
Cost poses another barrier. The newest GLP-1 drugs carry price tags exceeding $1,000 monthly, limiting access particularly in underserved communities where addiction often hits hardest. Insurance coverage varies. Some plans readily approve the drugs for diabetes or obesity but balk at off-label use for addiction, even as the death toll mounts and treatment capacity remains inadequate.
The review stops short of recommending GLP-1 drugs for addiction treatment outside clinical trials. Too many questions remain about dosing, duration, combination with existing therapies, and which patients might benefit most. But it makes clear that doing nothing isn’t working either. With 46 million American adults meeting criteria for substance use disorders and existing medications reaching so few, even a modest new tool could save lives.
Journal of the Endocrine Society: 10.1210/jendso/bvaf141
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