A promising group of medications already used to treat diabetes and obesity may also hold potential for tackling alcohol and drug addiction, according to a new study published in the Journal of the Endocrine Society.
These drugs, called Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), could represent a hopeful new direction for addressing alcohol and other substance use disorders.
“Early research in both animals and humans suggests that these treatments may help reduce alcohol and other substance use,” said lead researcher Lorenzo Leggio, M.D., Ph.D., of the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both part of the National Institutes of Health (NIH) in Bethesda, Md. “Some small clinical trials have also shown encouraging results.”
Current Treatment Options Are Limited
Substance use disorders are identified through four key patterns: physical dependence, risky behavior, social difficulties, and loss of control.
The widespread harm caused by these disorders extends far beyond individual health, affecting families, communities, and societies worldwide. Alcohol, in particular, is considered the most damaging drug overall, contributing not only to health problems but also to traffic accidents and incidents of violence, according to researchers.
Even with the scale of the problem, fewer than one in four people received treatment for alcohol or other substance use disorders in 2023.
The authors point to numerous barriers, including stigma and limited resources for patients and providers. “Current treatments for [alcohol and other substance use disorders] fall short of addressing public health needs,” the study noted.
GLP-1 Drugs and Their Potential Role in Addiction
GLP-1 medications have recently gained fame for their success in reducing appetite and promoting weight loss.
Beyond their effects on digestion, GLP-1 molecules play a major role in the brain. Activation of GLP-1 receptors in the central nervous system helps regulate hunger signals, prompting people to eat when hungry and stop when satisfied.
The study highlights that some forms of obesity share biological and neurological traits with addiction, though this idea remains debated.
“Pathways implicated in addiction also contribute to pathological overeating and obesity,” the study says.
Recognizing this overlap, scientists began exploring GLP-1 drugs as a possible treatment for substance use disorders. Early studies in animals and humans suggest that these drugs may influence the brain circuits that drive addictive behavior, potentially lowering cravings and use while also benefiting other coexisting health issues.
Evidence from Early Research
Studies that examine GLP-1 effects on substance use disorders include:
- Alcohol use disorder (AUD): A randomized controlled trial with exenatide, the first GLP-1receptor agonist approved for diabetes, showed no significant effect on alcohol consumption, although a secondary analysis indicated reduced alcohol intake in the subgroup of people with AUD and comorbid obesity. A more recent randomized controlled trial showed that low-dose semaglutide — a newer GLP-1 receptor agonist approved for both diabetes and obesity — reduced laboratory alcohol self-administration, as well as drinks per drinking days and craving, in people with AUD.
- Opioid use disorder: In rodent models, several GLP-1 receptor agonists have been shown to reduce self-administration of heroin, fentanyl and oxycodone. The studies also found that these medications reduce reinstatement of drug seeking, a rodent model of relapse in drug addiction.
- Tobacco use disorder: Preclinical data show that GLP-1 receptor agonists reduce nicotine self-administration, reinstatement of nicotine seeking, and other nicotine-related outcomes in rodents. Initial clinical trials suggest the potential for these medications to reduce cigarettes per day and prevent weight gain that often follows smoking cessation.
The Road Ahead
Leggio and his colleagues emphasize that more research is needed to confirm how effectively GLP-1 drugs treat addiction and to understand the underlying biological mechanisms.
Despite the unanswered questions, researchers remain optimistic.
“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,” Leggio said. “Finding new and better treatments is critically important to help people live healthier lives.”
Other study authors are Nirupam M. Srinivasan of the University of Galway in Galway, Ireland; Mehdi Farokhnia of NIDA and NIAAA; Lisa A. Farinelli of NIDA; and Anna Ferrulli of the University of Milan and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica in Milan, Italy.
Research reported in this article was supported in part by NIDA and NIAAA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
