Will blockbuster obesity drugs revolutionize addiction treatment?

Last April, neuroscientist Sue Gregson received an email from a man detailing his years-long struggle to break free from opioid addiction, first to opioids, then to the very drug that was intended to help him quit smoking.

The man had found research by Gregson suggesting that certain anti-obesity drugs could help reduce rats’ addiction to drugs such as heroin and fentanyl. He decided to try quitting again, this time while taking semaglutide, the blockbuster GLP-1 drug known as Ozempic. “That’s when he wrote to me,” says Gregson, who works at the Penn State University College of Medicine in Hershey. “He said he was clean of drugs and alcohol for the first time in his adult life.”

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Stories like this have spread rapidly in the past few years, through online forums, weight-loss clinics and news headlines. They describe people taking diabetes medications and weight-loss medications such as semaglutide (also marketed as Wegovy) and tirzepatide (sold as Mounjaro or Zepbound) who suddenly find themselves able to kick long-term addictions to cigarettes, alcohol, and other drugs. Now, clinical data is starting to support this idea.

Earlier this year, a team led by Christian Hendershot, a psychologist now at the University of Southern California in Los Angeles, reported in a landmark randomized trial that weekly injections of semaglutide reduced alcohol consumption.¹ – Key evidence that GLP-1 drugs can change addictive behavior in people with substance use disorder. More than a dozen randomized clinical studies testing GLP-1 drugs for addiction are now underway around the world, and some results are expected in the next few months.

Meanwhile, neuroscientists are working to discover how weight-loss drugs suppress addiction by acting on hormone receptors in areas of the brain that control desire, reward and motivation. They found that GLP-1 treatments help alleviate cravings for alcohol, opioids, nicotine, and cocaine through some of the same brain pathways that also work to calm hunger signals and overeating. “Ultimately, the neurobiological system that is activated by rewarding substances — food, sex, drugs, rock ‘n’ roll — is the same system,” says Roger McIntyre, a psychopharmacologist at the University of Toronto in Canada. Some researchers are testing whether drugs, by affecting brain circuits associated with reward, might help treat dementia and depression as well.

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Scientists warn that the research is still in its early stages. says W. “We first need to know if it’s effective and safe,” says Kyle Simmons, a neuroimaging specialist at Oklahoma State University in Tulsa, who is leading the GLP-1 alcohol reduction trial.

But some researchers and doctors are excited. No truly new category of addiction medicine has received regulatory approval in decades, says Elisabet Gerlhag Holm, an addiction biologist at the University of Gothenburg in Sweden. If GLP-1 drugs prove effective in larger trials, “it’s a revolution,” she says.

Laboratory to the spotlight

It has taken several years for the current buzz around GLP-1 drugs in addiction medicine to begin. Researchers originally developed it to control blood sugar in people with type 2 diabetes by mimicking the hormone GLP-1. It soon became clear that these drugs could suppress appetite and promote weight loss as well. They act on hormone receptors in the pancreas and intestines – where they help regulate blood sugar and signal satiety – but also on key areas of the brain that control reward and motivation, reducing the desire to eat tasty, calorie-laden food.

By early 2010, Gerlhag Holm was wondering whether drugs could mitigate other urges. It published three research papers showing that it can relieve cravings in alcoholic rats and mice²Nicotine³ And stimulants such as amphetamine and cocaine⁴. As her team showed⁵ GLP-1 treatment can reduce relapse-like animal behaviors, which is when people return to drugs after a period of abstinence.

However, she says her findings barely gained traction among addiction researchers, and pharmaceutical companies haven’t shown any interest either. “I’ve been alone for a long time,” says Gerlhag Holm.

But Lorenzo Leggio, a physician and scientist at the US National Institutes of Health in Baltimore, Maryland, noticed this work. He has also been tracking evidence that GLP-1 may influence addictive behavior, and in 2015, he joined forces with Gerlhag Holm to uncover the first evidence of a link between the hormone and alcoholism in humans. The team found that a common variant of the GLP-1 receptor gene is linked to heavy drinking⁶.

Using post-mortem human brain tissue, Liggio’s lab later showed that people with alcohol use disorder have elevated levels of GLP-1 receptors in key reward-related regions of the brain.⁷. Leggio believes this reflects an adaptive response: Alcohol suppresses the body’s production of GLP-1, so the brain enhances the expression of receptors for the hormone to maintain sensitivity to it in circuits that control reward and motivation.

These findings, combined with a growing number of animal studies, have strengthened the association of GLP-1 with addictive behavior. However, the story did not reach the public eye until May 2023. Atlantic A magazine published an article about people taking semaglutide who said their desire to smoke or drink had disappeared. “Did scientists accidentally invent an anti-addictive drug?” It was themed. “That was definitely a turning point,” says Leggio, who suddenly found himself fielding calls from reporters.

However, the first few rigorous experiments had largely disappointing results. A 2022 study in Denmark, led by psychiatrist Anders Fink Jensen at the University of Copenhagen, found that weekly treatment with exenatide — a “first-generation” GLP-1 compound used since 2005 to treat diabetes but never approved for weight loss — did not significantly reduce the number of heavy drinking days in people diagnosed with alcoholism.⁸. Likewise, a 2023 trial in Switzerland found that dulaglutide, another older GLP-1 drug, did not help people quit smoking.⁹.

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But other findings suggest that medications may have an effect. In a trial¹⁰ Involving 20 people with opioid use disorder, led by Gregson and psychologist Scott Pons, also of Pennsylvania State University, treatment with liraglutide — another first-generation GLP-1 drug — reduced opioid cravings by about 40%. When Fink-Jensen’s team used functional magnetic resonance imaging (fMRI) to look at the brains of people taking exenatide in their clinical trial, they saw muted activity in regions associated with reward when participants viewed images of alcoholic drinks.⁸.

But the first-generation drugs tested in these initial studies are much less effective than agents such as semaglutide or terzebatide. These second-generation compounds bind more tightly to the GLP-1 receptor, remain active in the body longer and have shown greater benefits across a range of health conditions. So, can these newer medications change the behavior of people struggling with drug abuse?

Buzz suppression

This is what researchers are now studying in a set of clinical trials, with highly anticipated results. Fink-Jensen and colleagues have already tested whether high-dose semaglutide approved for weight loss can reduce alcohol intake in 108 people with alcohol use disorder and obesity, in a clinical trial that ended earlier this year. He says the results should be published in early 2026.

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Meanwhile, in the United States, Liggio and Simons are leading independent but coordinated randomized trials testing semaglutide injections in moderate to heavy drinkers who meet diagnostic criteria for alcohol use problems. The Leggio trial will include 52 people and test a high dose of the drug Wegovy, while the Simmons trial, which includes 80 people, is testing a low dose of Ozempic, which is typically prescribed for diabetes. Psychologist Joseph Schacht, of the University of Colorado Anschutz Medical Campus in Aurora, conducted his own alcohol experiment using the oral version of semaglutide (marketed as Repulsus). By coordinating their efforts, the three teams hope to understand how differences in dose and delivery affect results.

Schacht says pills, although less effective than injections, can be more attractive to people with alcohol addiction, many of whom also have a history of using injectable drugs like fentanyl. “They can feel self-conscious about needles, because that’s a cue associated with injecting drug use,” he says.

In all of these trials of the drug semaglutide to treat alcoholism, the research teams are also using functional magnetic resonance imaging to take before-and-after snapshots of the brain to show how the drug changes responses to alcohol-related stimuli, such as drinks or images. This could reveal whether and how the drug disrupts the brain’s drive for alcohol, which is what fuels addiction. Imaging results may also show patterns of brain activity that are more common in people who benefit from GLP-1 treatment compared to those who do not. “This may give us a better understanding of who the drug works best for,” Simons says.

Anatomy of reward

Researchers are already piecing together a picture of how GLP-1 drugs act on the brain’s reward system. They know from animal models that rewarding substances — such as alcohol, nicotine, opioids and food — activate similar neural circuits. This connects deep brain structures such as the ventral tegmental area, where neurons that make the neurotransmitter dopamine originate, to the nucleus accumbens, where dopamine signals arrive and are registered as pleasure. Normally, every sip, puff or hit sends a jolt of rewarding dopamine through this circuit, teaching the brain to want more and reinforcing addictive behavior.

GLP-1 receptors are found on neurons throughout this network, and when stimulated, they are thought to reduce the flow of dopamine and other chemical messengers to make rewarding experiences less compelling. When drugs like semaglutide mimic GLP-1, they reduce the dopamine response and the desire to repeat addictive behavior fades.

Animal studies show that stress responses also play a role. When medications activate GLP-1 receptors in areas of the brain such as the amygdala, they help turn off the flow of stress hormones that accompany anxiety, withdrawal, and cravings. This dual action — calming craving and anxiety — could help explain why treatments seem to not only reduce consumption but also reduce relapse, at least in rodents.