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Testing GLP-1 Drugs for Substance Use Disorders

GLP-1 receptor agonist drugs, including liraglutide and semaglutide, are the basis for Ozempic, Wegovy, and other GLP-1 drugs prescribed for type 2 diabetes and off-label for the treatment of obesity. Over time, a growing chorus of anecdotal reports from people taking GLP-1 drugs indicates they might also be effective in reducing cravings for alcohol and opioids.

A huge number of trials have been launched to explore other uses for GLP-1 drugs besides type 2 diabetes. Trials have begun testing GLP-1 drugs as a treatment for heart disease, liver disease, Alzheimer’s disease, and an encyclopedia of other medical maladies. Most of the positive results derive from weight loss, as obesity is a factor in dozens of other medical conditions.

There is a growing interest in testing the use of GLP-1 drugs as a treatment for substance use disorders, matched by a seeming disinterest on the part of drug companies to conduct trials. The lack of studies comes down to money. Drug companies fear that if GLP-1 drugs are successful in treating addictions, they could be compelled to provide the drugs at cost to deal with a public health crisis.

Most of the studies of GLP-1 drugs for substance use disorders are academically funded. The British Journal of Pharmacology published a review of GLP-1 drugs for addiction disorders in 2021 and summarized the status of the research:

Studies in rodents and non-human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients.

Again, “trials have been initiated” but results are still wanting. Researchers writing in Nature Medicine in December 2023, caution against the premature off-label prescription of GLP-1 drugs for substance use disorders:

Some GLP-1RAs promote more weight loss than others, and so may be contraindicated for patients with normal or low weight. For example, special attention may be needed in patients with stimulant use disorders, given the known anorexigenic effects of psychostimulants.

In February of this year, researchers reported preliminary results of a clinical trial evaluating liraglutide for opioid use disorder. Twenty patients enrolled in a trial where half were given liraglutide and the other half a placebo. Full details of the study have not been published yet, but Dr. Patricia “Sue” Grigson-Kennedy of Penn State’s Neuroscience Institute reported at a meeting of the American Association for the Advancement of Science:

At higher doses of liraglutide, patients dropped out of the trial largely due to gastrointestinal symptoms including nausea.

We lack information on how many dropped out and how quickly. Cravings for opioids were reduced by 30% compared with the placebo group. The study was conducted in less than three weeks, so there’s no data available on the long-term benefits, with or without continued liraglutide treatments.

A recent summary of findings from clinical and preclinical studies of GLP-1 drugs for substance-use disorders published in the “Neuropharmacology” section of Frontiers in Pharmacology states that:

Although a GLP-1R agonist does not alter alcohol intake in AUD patients, it reduces this consumption in a sub-population of obese AUD individuals. Given the uncertainty of this outcome, additional clinical studies of obese AUD patients should explore the effects of the GLP-1R agonists on alcohol intake and body weight.

Specifically, the study being referred to was conducted in 2022 with 127 patients for alcohol use disorder enrolled in a 26-week trial with half receiving exenatide, a GLP-1 receptor agonist, and half receiving a placebo. The researchers report that “exenatide did not significantly reduce the number of heavy drinking days compared with placebo.” Heavy drinking days were significantly reduced in one sub-group: those with a BMI greater than 30kg/m2. A most puzzling outcome, indeed.

We look forward to seeing more studies of GLP-1 drugs for substance use disorders with non-obese individuals. Are they effective? Do they reduce cravings for normal-weight persons? How bad are the gastrointestinal events that have caused so many to abandon GLP-1 drugs? Is it dangerous for normal-weight persons to take GLP-1 drugs? We look forward to reporting on these questions at AddictionNews.

Written by Steve O’Keefe. First published July 8, 2024.


“Did Scientists Accidentally Invent an Anti-addiction Drug?,” The Atlantic, May 19, 2023.

“The role of glucagon-like peptide 1 (GLP-1) in addictive disorders,” British Journal of Pharmacology, September 2021.

“GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders,” Nature Medicine, December 2023.

“Taking a weight-loss drug reduced a craving for opioids,” ScienceNews, February 16, 2024.

“Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial,” JCI Insight, October 2022.

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