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Some people taking popular new diabetes and weight-loss drugs, including Ozempic, Wegovy, Zepbound, and Mounjaro, have reported reduced cravings for substances besides food. The medications seem to dampen the effects of drugs ranging from nicotine to alcohol, but scientists haven’t been able to fully figure out why.

A recent preliminary study in Scientific Reports offers clues to how the new class of drugs may make people drink less alcohol—and feel less drunk when they do. The study authors suggest that understanding the drugs’ mechanism in the entire body—not just the brain—could open up avenues for treating alcohol use disorder.

“There’s a lot of action in the brain, but what we were trying to argue in our paper is that there also is probably action in the gut,” says study co-author Alex DiFeliceantonio, an appetitive neuroscientist at Virginia Tech. “We need to look at both to really fully understand how these drugs are working to reduce the intake of substances with abuse liability.”

The drugs promote the release of insulin and ma

ke people feel full by mimicking the natural gut hormone glucagon-like peptide 1 (GLP-1). Scientists largely agree that the primary way GLP-1 drugs cause weight loss is through their effects on feelings of satiety in the brain—causing people to feel full faster and ultimately eat smaller meals. Past evidence suggests the brain’s pleasure and satiety pathways overlap, which has spurred researchers to propose that the GLP-1 drugs may be also quieting reward signals key in certain addictive behaviors, such as drinking alcohol.

But the drugs also cause a physiological reaction in the gut: they slow down the movement of food and liquids from the stomach into the small intestine, a process known as gastric emptying.

People taking these drugs “can’t eat quite as much, because the food is staying in their stomach longer,” DiFeliceantonio says. “The interesting thing about alcohol is it is not well absorbed in the stomach. It needs to empty into the intestine to be absorbed and for you to feel the effects.”

If the GLP-1 drugs delay gastric emptying, alcohol may take longer to reach the brain. “We know that slowing down a drug makes it less rewarding,” DiFeliceantonio says—and reducing reward may help treat addiction. “The substance matters, yes, but the speed at which it gets to your brain also matters,” she says.

DiFeliceantonio and her colleagues set out to test this hypothesis. In a makeshift bar in their lab, they gave vodka mixed in orange or cranberry juice to 10 people who were taking one of the GLP-1 medications for weight loss and a similar number of people in a control group. None of the participants had alcohol use disorder. In the span of an hour, all participants drank three vodka doses, calculated based on their body size, to increase their breath alcohol content (BrAC) to 0.08 percent. This is equivalent to a blood alcohol content (BAC) of 0.1 percent, past the legal limit for driving in the U.S.

The researchers surveyed the participants about how drunk they felt and took several breath alcohol measurements over four hours, or until the participants’ BrAC levels dropped below 0.02 percent.

“What we found was that, especially in the first 20 to 30 minutes after drinking the alcohol, there was a lower breath alcohol content in the group taking a GLP-1 receptor agonist, and they reported that they felt less drunk,” DiFeliceantonio says. All the participants reached similar BrAC levels after about an hour, but slowing the alcohol’s effect on the brain made people feel less intoxicated, she says.

Neither changes in blood glucose nor nausea (a common side effect of GLP-1 medications) explained how intoxicated people felt, the researchers found.

The study has several limitations. The sample size was small, and different participants were taking different weight-loss medications, which act on different gut hormone receptors or are prescribed at varying dosages. Ideally, in drug studies, researchers would keep the medication and dose consistent, but this study is a good start, says Carolina Haass-Koffler, an addiction researcher and associate professor of psychiatry at Brown University, who was not involved in the study.

“Alcohol use disorder is a complex, systemic disease and involves not only brain dysfunction but also a metabolic component,” Haass-Koffler says. “I really like the integration of the whole-body concept in this study.”

She notes, however, that introducing GLP-1 medications to a new population requires careful evaluation of the risks and benefits. “Safety data are out there for people with diabetes and now people taking the medication for obesity,” but the clinical presentation could be completely different in people with alcohol use disorder, Haass-Koffler says. DiFeliceantonio wouldn’t recommend GLP-1 drugs as future frontline treatments for someone with alcohol use disorder who is underweight.

Randomized controlled trials of these drugs have shown some promise in treating alcoholism. A 2022 clinical trial found that the early-generation GLP-1 medication exenatide lowered alcohol cravings in people with alcohol use disorder, and another trial published in February found that people with obesity and alcohol use disorder drank less when treated with semaglutide, the generic name for Wegovy and Ozempic.

“It seems like a really small thing, to just slow down [alcohol reaching the brain] a little,” DiFeliceantonio says. “From this study, we can’t definitively say this is the reason that people taking GLP-1 medications drink less, but it’s adding to this body of evidence of what the mechanism is.”

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