Can Ozempic cure addiction?

https://archive.is/1Zbeg

From the article:

When I asked addiction researchers about the promise of medications like Ozempic, they sounded as enthusiastic as Mary. GLP-1 medications—colloquially known as GLP-1s—mimic a naturally occurring hormone called glucagon-like peptide 1, which scientists have historically associated with digestion. In the traditional telling, after a meal, GLP-1 attaches to receptors in the pancreas, the gastrointestinal tract, and the brain; it stimulates the release of insulin, slows the passage of food through the stomach, and signals to our brains that we’re full. It breaks down within minutes. But it’s increasingly clear that GLP-1 affects much more than eating. GLP-1 drugs, which bind to the body’s receptors for hours or days, are now being studied for all sorts of addictions.

The results from the trial that Mary participated in should come out later this year, but a small study published in 2021 showed that smokers given exenatide, the first GLP-1 on the market, were nearly twice as likely to stop smoking as those given a placebo. An analysis of hundreds of thousands of electronic health records found that people with an addiction to opioids who happened to be prescribed GLP-1s were forty per cent less likely to overdose. Some scientists think that the medications may even help with behavioral addictions, such as gambling and compulsive shopping. Research into GLP-1s, scientists hope, could deepen our understanding of what addiction is. “Essentially all addiction medications to date have been specific to a particular type of addiction,” Heath D. Schmidt, a neuroscientist at the University of Pennsylvania, told me. “GLP-1s might be telling us that there’s some kind of universal pathology when it comes to addiction. And that they’re part of how we fix it.”

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Schacht is still analyzing data from the fifty people in his trial, but he shared some preliminary findings. Before the study, participants consumed nearly seven drinks a day; two months later, people on semaglutide drank half as much. The number of days on which they drank heavily—four or more drinks for women, five or more for men—fell from roughly two-thirds to a quarter. “My emotional response to alcohol was totally cut off,” Susan told me. Before she joined the study, if she found herself in the wine aisle of a grocery store, she’d buy five bottles. Afterward, she told me, “my brain recognized it—like, Oh, that’s what you used to want—but my body had no desire for it.” She said that when she repeated the cue-reactivity test at the end of the trial, the glass of wine “had absolutely no pull.” Strikingly, the drug didn’t make people any more likely to abstain from alcohol. It only led them to consume fewer drinks. “This, to me, is the most meaningful result,” Schacht said. “Most patients don’t want to be completely abstinent. They want to drink like a ‘normal person.’ ”

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These anecdotes raise the possibility that the so-called moderation molecule has an alter ego—as a desire dampener that can go too far. Maybe some people who take GLP-1s lose interest in drugs and alcohol because they lose interest in everything. In 2023, after scores of reports of suicidal thoughts and self-harm among people taking GLP-1s, the European Medicines Agency initiated a safety review. The agency ultimately concluded that the available evidence did not establish a causal link between the medications and suicidal thoughts or behaviors. (The U.S. Food and Drug Administration noted in 2024 that it could not “definitively rule out that a small risk may exist,” but requested last month that suicide warnings be removed from GLP-1 drugs.) The data remain frustratingly ambiguous. Observational studies, which tend to be less precise than randomized controlled trials, have found that GLP-1s might harm or help a person’s mental health. The Nature network of journals recently published an article suggesting that GLP-1s reduce the risk of suicidal thoughts by more than half—and another article saying that they more than double the risk of suicidal behavior. Nearly all the experts I spoke with said that we needed more research.

When we take a medicine in the hope that it will curb a particular desire, we’re meddling with a complex system, Sarah Kawasaki, the chief of addiction services at Penn State Health, told me. Kawasaki portrayed addiction as a legitimate evolutionary adaptation—the pursuit of pleasure—gone haywire. Enjoyment of food encouraged our ancestors to nourish themselves; enjoyment of sex encouraged them to procreate. “When it’s not in its extreme form, pleasure-seeking is what led to the success of this species,” Kawasaki said. Tampering with it can have side effects. “You need joy in life,” she told me. “What happens when you blanket a society in GLP-1s? Do we all turn into boring, listless people?” A small minority of the population seems to report anhedonia after taking GLP-1s, and other mental-health consequences—irritability, insomnia, apathy, brain fog—are probably only slightly more common. But the rapid spread of these medications is, essentially, a vast social experiment. Drugs are generally approved based on controlled studies of several hundred individuals. Now tens of millions of people are taking GLP-1s, and we’re discovering, in real time, the full range of their effects.

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Clinical trials have generally observed patients for weeks or months; addiction is a chronic disease that can last a lifetime. Even some of Grigson’s rats developed a tolerance to GLP-1s: after they’d been on a dose for a few weeks, their drug-seeking returned. “We’re in this phase right now where some people think these drugs cure everything,” Seeley said. “The hypothesis is that they target food, and then they have all these great spillover effects all over the place. My view is that the spillover is temporary. When the weight loss stops, the spillover stops.” If so, the medications could loosen the grip of an addiction temporarily, without inducing any kind of sustained sobriety. The GLP-1 bubble could still pop.