Can GLP-1 drugs treat addiction?

Researchers are investigating whether GLP-1 drugs could be used to treat addiction disorders, following patient reports of reduced cravings.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Flora Lichtman?

  Hi, I'm Flor 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, you know, if I'm doing this, maybe I try to go all the way and fully reset to a healthier lifestyle.

• 0:35Speaker 01

  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. You know, 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.

• 1:16Flora Lichtman?

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

• 1:23Speaker 01

  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? You know, 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 for drinking seemed to really vanish.

• 2:07Speaker 01

  It wasn't like a gradual thing. It was almost like an immediate light switch, you know, as soon as you started taking them.

• 2:17Flora 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 know? What are the risks? And do these drugs tell us anything new about the biology of addiction? Here with me is Dr. Joseph Schocht, the co-director of the Division of Addiction Science Prevention and Treatment at the University of Colorado Anshu 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.

• 3:02Speaker 02

  Thank you. Happy to be here.

• 3:04Speaker 03

  Thanks so much for having me.

• 3:05Flora Lichtman?

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

• 3:12Speaker 02

  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?

• 3:35Flora 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?

• 3:47Speaker 03

  That's a great question. So I think that there are sort of 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 the GLP-1s are experiencing

• 4:32Speaker 03

  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 Exentatide or Bedurion. 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 Azempic, 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.

• 5:17Speaker 03

  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.

• 5:41Flora Lichtman?

  Yeah, I mean, we know with food that these drugs can make you feel sick, you know, that 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?

• 5:58Speaker 03

  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, but 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's specific 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.

• 6:44Speaker 03

  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.

• 6:55Flora Lichtman?

  Sarah?

• 6:56Speaker 02

  I think, you know, addiction is such a complex thing. It's not just presence or absence of, you know, 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, you know, exercise. The use typically doesn't come out of nowhere, right? 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,

• 7:37Speaker 02

  to not have to experience overwhelming emotions, to not have to, you know, deal with horrific memories of trauma, things like that. And so, you know, 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 way of dealing with these things, you know, I would argue that the medication has to be supplemented with other, you know, behavioral health services because, you know, 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, you know, yearning to avoid and escape are

• 8:22Speaker 02

  going to come flooding back.

• 8:24Flora Lichtman?

  Right, so even if you get rid of cravings, there's a lot more to addiction than just that biochemistry.

• 8:33Speaker 02

  Absolutely.

• 8:35Flora 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.

• 8:54Speaker 04

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• 9:52Speaker 05

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• 10:06Flora Lichtman?

  Jo, 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?

• 10:21Speaker 03

  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.

• 11:04Speaker 03

  These drugs are of course also affecting the GLP-1 that your body naturally 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's easier for different things to cross into the brain. And that, again, that this may be one reason that GLP-1s perhaps are more effective in reducing substance use for people with alcohol use disorder than than other drugs.

• 11:42Flora Lichtman?

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

• 11:52Speaker 03

  I don't think we have enough data to know yet. There are some intriguing electronic medical 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.

• 12:33Flora Lichtman?

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

• 12:37Speaker 01

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

• 12:52Speaker 01

  You see any evidence of that?

• 12:54Speaker 02

  Absolutely. You know, 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, you know, a year, five years, several decades, we're building new neuropathways. 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. Right? So, and that's why I think it's so important that, you know, medication alone cannot be the answer.

• 13:30Flora Lichtman?

  Is there stigma around using medication for addiction?

• 13:34Speaker 02

  Definitely. It can certainly be pretty stigmatizing. I think when you're, we're also thinking about some of the more, you know, 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're using these medications. I don't personally subscribe to that. I think anything that can help you, you know, 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

• 14:17Speaker 02

  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.

• 14:28Flora Lichtman?

  They also seem to, you know, we've seen this in food. They show that it's not a willpower issue, right? That there's underlying biology here. And I wonder if, if that might be at play in addiction too.

• 14:43Speaker 03

  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 use 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.

• 15:23Flora 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?

• 15:38Speaker 02

  I really appreciate that point because I think that 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.

• 16:10Flora Lichtman?

  Sarah, are you concerned about access with these drugs?

• 16:13Speaker 02

  Absolutely. That is my other really big sticking point. I think if we're serious about utilizing something like this as a life-saving 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. 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?

• 16:57Flora Lichtman?

  Does the fact that these drugs are showing promise for drugs and alcohol suggests anything new about addiction? You know, does it suggest a sort of grand unified mechanism at work for addiction, Joe?

• 17:12Speaker 03

  That's a wonderful question. You know, 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 alcohol substance use disorders is telling us, is suggesting, is that there may be this kind of final common pathway,

• 17:55Speaker 03

  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.

• 18:12Flora 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?

• 18:22Speaker 03

  I think it's too early to do that. I would, much too early. Alcohol and substance 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

• 19:03Speaker 03

  see those data and will be able to make informed choices about for whom these medications should be prescribed for alcohol substance use disorders.

• 19:12Flora Lichtman?

  Sarah Karstens, Addiction Clinical Director of Outpatient Services at Penn Medicine's Princeton House Behavioral Health, and Dr. Joseph Schocht, Associate Professor in the Department of Psychiatry at the University of Colorado Anschutz School of Medicine. Thank you both for joining me today.

• 19:28Speaker 03

  Thanks so much.

• 19:29Speaker 02

  Thank you for having us.

• 19:31Flora Lichtman?

  This podcast was produced by Shoshana 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-CY-FRY is our number, 877-4-CY-FRY. Thank you for listening. I'm Flora Lichtman.