Last April, neuroscientist Sue Grigson received an e-mail from a man detailing his years-long struggle to kick addiction — first to opioids, and then to the very medication meant to help him quit.
The man had stumbled on research by Grigson, suggesting that certain anti-obesity medications could help to 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 better known as Ozempic. “That’s when he wrote to me,” says Grigson, who works at Pennsylvania State University College of Medicine in Hershey. “He said that he was drug- and alcohol-free for the first time in his adult life.”
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Stories like this have been spreading fast in the past few years, through online forums, weight-loss clinics and news headlines. They describe people taking diabetes and weight-loss drugs such as semaglutide (also marketed as Wegovy) and tirzepatide (sold as Mounjaro or Zepbound) who find themselves suddenly able to shake long-standing addictions to cigarettes, alcohol and other drugs. And now, clinical data are starting to back them up.
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 cut alcohol consumption1 — a key demonstration that GLP-1 drugs can alter addictive behaviour in people with a substance-use disorder. More than a dozen randomized clinical studies testing GLP-1 drugs for addiction are now under way worldwide, with some results expected in the next few months.
Neuroscientists, meanwhile, are working out how the weight-loss drugs suppress addiction by acting on hormone receptors in brain regions that control craving, reward and motivation. They are finding that GLP-1 therapies help to blunt urges for alcohol, opioids, nicotine and cocaine through some of the same brain pathways that also quell hunger cues and overeating. “At the end of the day, the neurobiological system that is activated by rewarding substances — food, sex, drugs, rock and roll — it’s the same system,” says Roger McIntyre, a psychopharmacologist at the University of Toronto in Canada. And some researchers are testing whether, by influencing reward-related brain circuits, the drugs might help with dementia and depression as well.
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The research is still in its early stages, scientists warn. “We first need to find out if it’s efficacious and safe,” says W. Kyle Simmons, a neuroimaging specialist at Oklahoma State University in Tulsa, who is leading a GLP-1 trial for alcohol reduction.
But some researchers and physicians are excited. No truly new class of addiction medicine has won approval from regulators in decades, says Elisabet Jerlhag Holm, an addiction biologist at the University of Gothenburg in Sweden. If GLP-1 drugs prove effective in bigger trials, she says, “it’s a revolution”.
Laboratory to limelight
It took some years for the current buzz around GLP-1 drugs in addiction medicine to build. Researchers originally developed them to control blood sugar in people with type 2 diabetes by mimicking the hormone GLP-1. Soon it became clear that the drugs could curb appetite and promote weight loss, too. They act on hormone receptors located in the pancreas and gut — where they help to regulate blood sugar and signal fullness — but also in key regions of the brain that control reward and motivation, dialling down the urge for tasty, calorie-laden food.
By the early 2010s, Jerlhag Holm was wondering whether the drugs could blunt other urges. She published a trio of papers showing that they could dampen cravings in rats and mice hooked on alcohol2, nicotine3 and stimulants such as amphetamine and cocaine4. Her team also showed5 that GLP-1 therapy could reduce animal behaviours that resemble relapse, which is when people return to drugs after a period of abstinence.
Some people report anecdotally that GLP-1 drugs are helping them to quit long-standing nicotine addictions.Credit: Tolga Akmen/AFP/Getty
Yet her findings barely registered among addiction researchers, she says, and pharmaceutical companies showed no interest either. “I was quite alone for a long time,” says Jerlhag Holm.
But Lorenzo Leggio, a physician-scientist at the US National Institutes of Health in Baltimore, Maryland, noticed the work. He had also been following clues that GLP-1 might influence addictive behaviour and, in 2015, joined forces with Jerlhag Holm to uncover the first evidence of a connection between the hormone and alcohol dependence in humans. The team found that a common variant of the GLP-1 receptor gene was linked to heavier drinking6.
Using post-mortem human brain tissue, Leggio’s lab later showed that people with alcohol-use disorder have elevated levels of GLP-1 receptors in key reward-related regions of the brain7. Leggio suspects that this reflects an adaptive response: alcohol dampens the body’s GLP-1 production, and so the brain boosts expression of the hormone’s receptors to preserve sensitivity to it in circuits that govern reward and motivation.
These results, together with a growing number of animal studies, solidified GLP-1’s connection to addictive behaviour. Yet it was not until May 2023 that the story spilled into the public eye. The Atlantic magazine published an article about people taking semaglutide who said their urge to smoke or drink had faded. ‘Did Scientists Accidentally Invent an Anti-addiction Drug?’ it was headlined. “That was definitely a turning point,” says Leggio, who suddenly found himself getting calls from journalists.
The first few rigorous trials, however, 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 substantially reduce the number of heavy drinking days in people diagnosed with alcohol dependence8. A 2023 trial in Switzerland likewise found that dulaglutide, another older GLP-1 drug, did not help people to quit smoking9.
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But other results suggested that the drugs might have an effect. In a trial10 involving 20 people with opioid-use disorder, led by Grigson and psychologist Scott Bunce, also at Pennsylvania State University, treatment with liraglutide — another first-generation GLP-1 drug — reduced opioid craving by roughly 40%. And 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 reward-related regions when the participants viewed images of alcoholic drinks8.
But the first-generation drugs tested in these preliminary studies are much less potent than agents such as semaglutide or tirzepatide. These second-generation compounds bind more tightly to the GLP-1 receptor, stay active in the body for longer and have shown greater benefits across a range of health conditions. So, could these latest drugs change the behaviour of people struggling with substance misuse?
Blunting the buzz
That’s what researchers are now examining in a raft of clinical trials with hotly anticipated results. Fink-Jensen and his colleagues have already tested whether the high dose of semaglutide approved for weight loss can cut alcohol intake in 108 people with alcohol-use disorder and obesity, in a clinical trial that wrapped up earlier this year. He says the results should be published in early 2026.
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In the United States, meanwhile, Leggio and Simmons are each leading independent but coordinated randomized trials testing injected semaglutide in moderate-to-heavy drinkers who meet the diagnostic criteria for problematic alcohol use. Leggio’s trial will involve 52 people and test the high-dose Wegovy form of the drug, whereas Simmons’s trial, involving 80 people, is testing the lower-dose Ozempic, typically prescribed for diabetes. And psychologist Joseph Schacht at the University of Colorado Anschutz Medical Campus in Aurora has been running his own alcohol trial with the oral version of semaglutide (marketed as Rybelsus). By coordinating their efforts, the three teams hope to tease apart how differences in dose and delivery affect outcomes.
Schacht says that the pills, although less potent than injections, could be more appealing to people with alcohol addiction, many of whom also have a history of using injectable drugs such as fentanyl. “They can be gun-shy around needles, because that is a cue related to injection drug use,” he says.
In all of these trials of semaglutide for alcohol dependence, the research teams are also using fMRI to capture before-and-after snapshots of the brain to show how the drug alters responses to alcohol-related prompts, such as drinks or photos. This could reveal whether and how the drug disrupts the brain’s drive for alcohol — the reward-seeking sense of ‘wanting’ that fuels addiction. The imaging results might also show brain activity patterns that are more common in people who benefit from GLP-1 therapy than in those who don’t. “It may give us a better understanding for whom the drug works best,” Simmons 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 — alcohol, nicotine, opioids, food — activate similar neural circuitry. This links deep brain structures such as the ventral tegmental area, where neurons that synthesize the neurotransmitter dopamine originate, to the nucleus accumbens, where dopamine signals arrive and register 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 behaviour.
GLP-1 receptors sit on neurons throughout this network and, when triggered, are thought to reduce the flow of dopamine and other chemical messages to make rewarding experiences feel less compelling. When drugs such as semaglutide mimic GLP-1, they blunt the dopamine response and the compulsion to repeat the addictive behaviour fades away.
Stress responses come into play as well, animal studies show. When drugs activate GLP-1 receptors in brain regions such as the amygdala, they help to mute the surge of stress hormones that accompany anxiety, withdrawal and craving. This dual action — calming both the urge and the unease — could help to explain why the therapies seem to reduce not only consumption but also relapse, at least in rodents.
