Can GLP-1 drugs treat addiction?

FLORA LICHTMAN: Hi. I’m Flora Lichtman, and you’re listening to Science Friday.

GLP-1s– Ozempic, Wegovy, Zepbound. You know what I’m talking about– are prescribed for weight loss, diabetes, blood-sugar management. But as more people take them, patients are reporting an off-label use. We got a call from one of our listeners, Brian from Wisconsin. About a year ago, he decided to get on a GLP-1 to manage his diabetes. But he thought, if I’m doing this, maybe I try to go all the way and fully reset to a healthier lifestyle.

BRIAN: And I just decided to change everything at that point in my life. So that included cutting out alcohol, which I’ve had a long, complicated relationship with over the years. Typical rural Wisconsin-type drinking since I was 12, beers here and there with buddies all throughout high school. I suffered from a lot of depression, anxiety. And you’re in Wisconsin, and you’re in a college town, and the drinking culture is huge. So it was pretty easy to self-medicate.

FLORA LICHTMAN: In the years since, Brian tried not to drink so much, but it was hard to get alcohol off his mind.

BRIAN: You still plan everything around when you’re going to be able to drink. Are you going to have enough to drink? Are you going to have to stop at this place first before you go home? all the little things you do that you don’t realize. And I thought if I was going to try to do something positive for my health around the time when I was diagnosed with diabetes, then why not just quit drinking also?

And it was strange because, really, the cravings things for drinking seemed to really vanish. It wasn’t like a gradual thing. It was almost like an immediate light switch as soon as you started taking them.

FLORA LICHTMAN: Brian’s not the only one to report this. In fact, researchers are actively investigating whether GLP-1s might be effective for treating alcohol and drug addiction. So how much do we? What are the risks? And do these drugs tell us anything new about the biology of addiction?

Here with me is Dr. Joseph Schacht, the codirector of the Division of Addiction Science, Prevention, and Treatment at the University of Colorado Anschutz School of Medicine. He’s running a randomized clinical trial on GLP-1s and alcohol use. And we have Sarah Carstens, the addictions clinical director of outpatient services at Penn Medicine’s Princeton House Behavioral Health. She works directly with patients. Sarah, Joe, thank you for being here.

SARAH CARSTENS: Thank you. Happy to be here.

JOSEPH SCHACHT: Thanks so much for having me.

FLORA LICHTMAN: Sarah, we know Brian’s not the only one reporting this. Have you heard stories like this from your patients?

SARAH CARSTENS: So we have not had any patients who have specifically been on this medication that have been reporting significant changes to their use patterns, though it absolutely has been a topic of conversation, just people hearing that this is something that’s happening and wondering, is this something that could be helpful for them in the future?

FLORA LICHTMAN: Joe, I mean, is the data– I know you’re running a trial, but is the data on GLP-1s for alcohol addiction/drug addiction still mostly anecdotal? Where does that stand?

JOSEPH SCHACHT: That’s a great question. So I think that there are three lines of evidence that are in different stages. The first one is some of these preclinical or animal models of alcohol addiction, and those models go back now 10, 15 years with GLP-1 agonists and suggest that these types of drugs reduce alcohol consumption and use of other substances in animals.

The second part of the story is some of these studies of electronic medical records taken from large health systems in which you have tens of thousands of people, again, taking these medications for other indications, for obesity or diabetes. Those studies also very consistently show that people taking GLP-1s are experiencing fewer of these alcohol-related things in the medical chart.

And the third piece of the story and the one that’s the least developed but is the most important, of course, is the randomized-clinical-trial evidence, and there we now have two studies of GLP-1 agonists for alcohol-use disorder, one of which was negative using an older drug called exenatide or Bydureon. That study was negative, although it suggested in the patients with the highest body weights that they did drink less when they were given the GLP-1 agonist.

The other study is a study of Ozempic, of injectable semaglutide, a small study of 50 patients conducted at the University of North Carolina. These were non-treatment-seeking patients. And so they were drinking quite heavily, but they were not trying to stop or cut down on their drinking. And the study suggested that they experienced less alcohol craving and also consumed less alcohol during the time that they were on the GLP-1 agonist.

But that’s just one small study so far. We’re really waiting on more of the clinical-trial evidence to come in, and there are a number of studies, mine and others, ongoing right now. We anticipate that in the next six months, we’ll know quite a lot more from the clinical-trial perspective about the efficacy of these drugs.

FLORA LICHTMAN: Yeah, I mean, and we know with food that these drugs can make you feel sick, that just the idea of eating becomes unappealing. If that’s the mechanism working for alcohol here, is that the same as dampening a craving?

JOSEPH SCHACHT: Yeah, I would really differentiate those things, actually. So, first, I completely agree GLP-1 agonists absolutely cause gastrointestinal side effects. They don’t do that for everyone. If you look at the clinical trial data, typically it’s 30% to 40% of patients experience those side effects. They tend to be somewhat transient. They’re not all the time. And we think we see these effects for alcohol use, for other drugs over a more sustained period of time. It’s not like you stop drinking for the week that you have the side effects, and then you go right back to it.

The thing that I think is happening with GLP-1s– again, and that specific’s perhaps to the caloric part of alcohol– is that they are taking away the motivation to drink. They’re not making you sick and feeling like you don’t want to drink because you’re sick. They’re taking away your interest in drinking in the first place, your desire to do that, and that’s a very different biological pathway than gastrointestinal side effects.

FLORA LICHTMAN: Sarah?

SARAH CARSTENS: I think addiction is such a complex thing. It’s not just presence or absence of the substance use in and of itself. That is certainly a part of it. There are all of the physiological components, of course, which medications like this would certainly help to manage, but there are also a lot of other factors. There are the environmental factors, relationships, food, nutrition, exercise.

The use typically doesn’t come out of nowhere. So why were they drinking in the first place? What was causing the alcohol use? And again, in my experience, very typically it is to not have to feel something else, to not have to experience overwhelming emotions, to not have to deal with horrific memories of trauma, things like that. And so the alcohol or other substance use becomes the way in which they’re escaping that.

And so it just makes me wonder if we’re taking away this kind of coping skill or way of dealing with these things, I would argue that the medication has to be supplemented with other behavioral health services because if we’re taking away that skill, we’ve got to put something in place because all of those emotions, all of those things that they have been yearning to avoid and escape are going to come flooding back.

FLORA LICHTMAN: Right. So even if you get rid of cravings, there’s a lot more to addiction than just that biochemistry.

SARAH CARSTENS: Absolutely.

FLORA LICHTMAN: After the break, I want to dig into the mechanism or the possible mechanism of how these drugs might work for addiction and what these findings might tell us about the biology of addiction. Stay with us.

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Joe, I know the studies are still underway that will give us more clarity about how effective these drugs are for alcohol and other substances, but do we have a sense of the possible mechanism of how GLP-1s might work on addiction?

JOSEPH SCHACHT: That is really still an area of investigation. We know that there are GLP-1 receptors in the parts of the brain that fundamentally contribute to craving and to wanting things and to being unable to control use of alcohol or other substances. Those are parts of the brain like the nucleus accumbens, which is in the basal ganglia, the lizard part of the brain.

We don’t know if these GLP-1 agonist drugs are able to access those parts of the brain. For various reasons related to how they’re produced, they may not be able to easily cross what’s called the blood-brain barrier. And so it’s possible that some of these effects are being produced through some secondary mechanism. These drugs are, of course, also affecting the GLP-1 that your body naturally actually produces. It’s possible that that mechanism is translating into the brain somehow. It’s also possible that these drugs are crossing into the brain.

One interesting theory I’ve heard is that in people with a long history of alcohol-use disorder of heavy drinking that the blood-brain barrier becomes leakier, that it’s easier for different things to cross into the brain, and that, again, this may be one reason that GLP-1s perhaps are more effective in reducing substance use for people with alcohol-use disorder than other drugs.

FLORA LICHTMAN: Do we know if GLP-1s might work better for some drugs than others? Do we have enough data to know?

JOSEPH SCHACHT: I don’t think we have enough data to know yet. There are some intriguing electronic-medical-records studies out there suggesting that there seems to be a signal for other drugs besides alcohol, that we also see fewer prescriptions for smoking-cessation medications, for example, in patients prescribed GLP-1 drugs versus non-GLP-1 drugs.

The interesting thing, I think, about alcohol, unlike all other drugs of abuse, is that alcohol is a caloric substance, and the GLP-1 drug may be reducing that drive for those calories, in some ways sort of incidental to the fact that those calories are coming from alcohol versus something else.

FLORA LICHTMAN: Our listener Brian, who shared his story at the top, had a question.

BRIAN: Once you do stop a certain behavior, is there any evidence that the brain will rewire itself in terms of its way that it thinks about addiction? Do you see any evidence of that?

SARAH CARSTENS: Absolutely. New behavior can spawn new behavior. When we’re engaging in different patterns of behavior that are contrary to what we’ve been doing for a year, five years, several decades, we’re building new neural pathways. And when we do those things enough, when we engage in these new behaviors enough, that will help that to become essentially our new default setting. And that’s why I think it’s so important that medication alone cannot be the answer.

FLORA LICHTMAN: Is there a stigma around using medication for addiction?

SARAH CARSTENS: Definitely. It can certainly be pretty stigmatizing. I think when we’re also thinking about some of the more traditional recovery networks, we think about AA and NA, and there are definitely schools of thought within those camps that you’re not really in recovery if you are using these medications. I don’t personally subscribe to that. I think anything that can help you live your fullest life is what you need to do.

I think where GLP-1s may actually have a benefit is that they’ve seen such success in other arenas that my hope would certainly be that people would not be as afraid to try something like this and that it would actually be a bit less stigmatizing than some of the other medications that are available within addiction medicine right now.

FLORA LICHTMAN: They also seem to– we’ve seen this in food. They show that it’s not a willpower issue, that there’s underlying biology here. And I wonder if that might be at play in addiction too?

JOSEPH SCHACHT: I think that is such a profoundly important point, just to jump in. I have spent my career studying medications for alcohol and substance-use disorders. One of the other things that we really struggle with is this perception that addiction, the substance-abuse disorders are diseases of willpower, that people could choose to be better if they wanted to, that they’re choosing to do this, and that they have the ability to stop.

That’s not the case. These are diseases of the brain. They’re diseases of neurobiology. But the fact that a medication can reverse some of this I think allows people to see that in a different way, and understanding that is critical to treating these disorders compassionately.

FLORA LICHTMAN: I mean, on the other hand, we’re seeing some people eating way too little on these drugs and developing nutritional deficiencies. Are there risks to giving this drug to people who don’t have any weight to lose?

SARAH CARSTENS: I really appreciate that point because I think that has definitely been one of the things that has been on my mind a lot. What is this going to look like for people who are already at a deficit in terms of their nutritional status because of the years of alcohol use and how that translates? And what does the follow-up look like? Are we recommending nutritionists? Are we working with them to ensure proper caloric intake and all of that? So I really appreciate that point.

FLORA LICHTMAN: Sarah, are you concerned about access with these drugs?

SARAH CARSTENS: Absolutely. That is my other really big sticking point. I think if we’re serious about utilizing something like this as a lifesaving measure for folks, access has to be a consideration. And not just access but I think in terms of the research that is being done, representation as well, right, because who is utilizing this right now is not necessarily representative of every group that could really benefit from this. And so I think it’s really important to make sure that we’re looking at ensuring that this is going to work. For whom is this going to work? And then are those folks able to afford it?

FLORA LICHTMAN: Does the fact that these drugs are showing promise for drugs and alcohol suggest anything new about addiction? Does it suggest a sort of grand unified mechanism at work for addiction? Joe?

JOSEPH SCHACHT: That’s a wonderful question. There’s been a long history of overlap between eating and weight loss and addiction medications in particular. So some of the medications that are currently approved or often used to treat alcohol-use disorder in particular are also weight-loss drugs. For example, the drug naltrexone– that’s an opioid antagonist. It’s also approved in combination with another drug as a weight-loss drug. And so that suggests that there’s some overlapping pathways there.

I think what the potential efficacy of GLP-1 agonists for substance-use disorders is telling us, is suggesting is that there may be this kind of final common pathway, this core underlying biology of desire, of wanting things that may transcend food or alcohol or other things and may reflect something fundamental about the way the brain processes these feelings.

FLORA LICHTMAN: What would you say to people who are struggling with addiction who might hear this or read about this and think, maybe I should experiment on myself?

JOSEPH SCHACHT: I think it’s too early to do that, much too early. Alcohol and substance-use disorders are very challenging to treat. We don’t have medications that are strongly effective or effective for everyone. And so I can understand where that frustration comes from. And people might say, well, I’m going to try this because nothing else has worked. On the other hand, we don’t have all of the clinical trial data in yet. I think that we very soon will, and so I would encourage people to wait a little bit longer as the results of those trials are published in the next six months to a year and that prescribers who might writing the prescriptions for these medications will see those data and will be able to make informed choices about for whom these medications should be prescribed for alcohol or substance-use disorders.

FLORA LICHTMAN: Sarah Carstens, addiction clinical director of outpatient services at Penn Medicine’s Princeton House Behavioral Health and Doctor Joseph Schacht, associate professor in the Department of Psychiatry at the University of Colorado Anschutz School of Medicine, thank you both for joining me today.

JOSEPH SCHACHT: Thanks so much.

SARAH CARSTENS: Thank you for having us.

FLORA LICHTMAN: This podcast was produced by Shoshannah Buxbaum with an assist from Kathleen Davis. Thank you to everyone who called us with your stories. We listened to every single one of them, and we were really moved to hear them and that you would share them with us.

If you’d like to call us with a question or a comment or a story idea, the listener line is always open. 877-4-SCIFRI is our number. 877-4-SCIFRI. Thank you for listening. I’m Flora Lichtman.

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