Semaglutide (Ozempic, Wegovy) and other drugs in its class are widely known for their role in managing type 2 diabetes and suppressing appetite. They may also prove useful one day for curbing certain addictive behaviors such as alcohol use and smoking, according to research.
Preclinical research has shown promising results, and endocrinologists and patients alike have described, anecdotally, reduced cravings for alcohol, shopping and even coffee.
“The consistency I hear from all patient groups is gaining control, whereas previously there was loss of control,” Gitanjali Srivastava, MD, internist and obesity medicine program director at Vanderbilt University Medical Center in Nashville, Tennessee, told MedPage Today. “Suddenly, there’s a calm. It’s like the calm after the storm.”
In addition to dampening previously binge eating, patients described feeling like “a valve has been closed” on a number of other behaviors after starting the drug, Srivastava said. “Suddenly I’m able to step back and say, ‘Oh, well, I had this shopping phenomenon that was going on, gambling or addiction or alcoholism, and suddenly it just stopped.'”
However, the precise mechanisms underlying the effects of semaglutide and other GLP-1 agonists on behaviors such as smoking and alcohol consumption are not well understood. Researchers are in the early stages of studying the use of this drug class for addictive behaviors in humans, and experts said unanswered questions about a potential addictive indication for semaglutide should elicit attention — and caution — from of the prescribers.
Semaglutide modulates insulin release through the pancreas, which is how it helps people with type 2 diabetes control their blood sugar. But it also works in the brain via GLP-1.
“If we look at where the GLP-1 receptor is in the brain, it’s really widely distributed. So, it’s in many brain centers in the nuclei that would be associated with these types of behaviors,” Daniel Drucker, MD, of Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, he told MedPage Today.
“The challenge we have is we have the anecdotal reports, which are pretty prevalent. We have a lot of doctors reporting it and a lot of people on social media reporting their experiences. What we don’t have are definitive randomized controlled trials,” he said. added.
Over the years, animal studies have shown similar reactions to other GLP-1 agonists such as liraglutide (Saxenda), which suppressed or reduced alcohol consumption in rats and African vervets. Studies of exenatide (Byetta) and opioid-related behaviors had mixed results, although it reduced nicotine intake in mice.
While Drucker said the mechanisms behind an effect like this “aren’t very well defined,” one could have to do with dopamine availability. “GLP-1 will suppress the amount of dopamine or dopamine transporters, implying, indirectly…that somehow we don’t get as much pleasure or get as much reward because dopamine is induced by many of these substances we take in, which is part of the pleasure of taking them.”
Another may have to do with the neurotransmitter GABA. Lorenzo Leggio, MD, Ph.D., of the National Institute on Alcohol Abuse and Alcoholism, co-authored a recent study that found that semaglutide reduced “binge-like” alcohol consumption and alcohol dependence in mice, respectively and in rats. This was true in both males and females, and the rodents also showed an aversion to a sugary solution.
Leggio said drugs used for alcohol use disorder, such as acamprosate (Campral), act on GABA.
In the study, “we showed that semaglutide is affecting some of the key addiction-related factors in our brain, such as dopamine and GABA,” Leggio told MedPage Today. “So it’s another piece of the cake, another piece of evidence that semaglutide is working those systems in the brain that we know are important to addiction.”
Leggio is now working on a protocol for a randomized controlled trial that will look at semaglutide and alcohol use in humans, and is collaborating with Oklahoma State University on a similar study.
There’s still some disagreement about exactly how GLP-1 signals are sent in the gut and brain, he said. What he and others are studying is how GLP-1 made in the brain and GLP-1 made in the gut interact, which could inform whether the effects of semaglutide in reducing alcohol consumption are related to the effects of semaglutide in the body. .
But doctors like Srivastava and Jody Dushay, MD, an endocrinologist at Beth Israel Deaconess Medical Center in Boston, have noticed real-world signs.
Dushay told MedPage Today that a small number of his patients taking GLP-1 agonists have reduced cravings or use of alcohol. “Anecdotally, it’s true,” she said. However, “I’ve only heard people mention it spontaneously, so it’s a really small number of people who mentioned alcohol.”
Few of Dushay’s patients smoke, he added, and he hadn’t heard from patients other behaviors like shopping or using the phone.
Dushay also wondered if a common side effect of semaglutide might also play a role in aversion to alcohol: nausea, which about 85 percent of her patients estimated to have some extent.
“Some people might say, ‘I’m not nauseous and I don’t really feel like drinking,'” she said. “And other people are like, ‘I’m so sick, I don’t even want to have a drink.’ So, it could be one or the other. Or it could be both.”
However, the nausea is usually short-lived as patients develop a tolerance to semaglutide. It is also possible, said Dushay and others, that a general dampening of pleasure responses underlies the phenomenon.
“It’s not entirely surprising that some people can feel like they don’t get pleasure from activities they enjoyed before,” she noted. “It might just be the case that… he doesn’t scratch his itch anymore.”
Experts have also warned of the potential risk of serious mental health problems that could result from what is known as anhedonia, the reduced ability to experience pleasure. Wegovy’s labeling carries a warning about suicidal ideation and advises against prescribing it to patients with a history of suicidal thoughts.
“This is exactly why we need to do double-blind placebo-controlled studies, to look not only at efficacy, as we hope, but also at safety, specifically, because people with alcohol use disorder and addiction in general they often have comorbidity with other mental health problems, including depression,” Leggio said, emphasizing the importance of monitoring depressive symptoms closely.
But, he added, “we’re definitely…not concerned based on what we know so far because semaglutide is being prescribed worldwide and there have been no red flags.”
Another big unknown, Drucker noted, is the dose-response relationship needed to produce suppression of addictive behaviors, versus weight loss and diabetes control.
“Are they identical? If so, do I really not want everyone to lose weight if they’re trying to necessarily quit smoking or reduce their addiction, or can we get away with lower doses than needed to achieve weight loss?” Drucker said. “That’s a really interesting question. And we don’t have good data to answer it.”
Ultimately, experts agree, all patients are different, and there’s still no way to predict how someone will respond to semaglutide and other GLP-1 agonists.
“It’s nice to be aware, as someone who prescribes them frequently, that you need to ask patients about all of this and not just look at ‘how many pounds have you lost?'” Dushay said. “Truly [ask], ‘what is this drug doing in your body?’ and start asking a wider range of questions, rather than putting someone on the scale and titrating a dose.”
“Do you think semaglutide will drastically save the world from addiction? The answer is no,” Leggio said. “If you asked me, ‘Do you think semaglutide is a promising drug to help people with alcohol use disorder?’ I think the answer is yes.”
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