Rethinking addiction in the age of Ozempic

0:00Support for this podcast and the following message come from Allianz Travel Insurance. Ready to turn last year's travel dreams into this year's jet-setting reality? An AllTrips annual plan is ready when you are all year long. Learn more at AllianzTravelInsurance.com. This is the TED Radio Hour. Each week, groundbreaking TED Talks. Our job now is to dream big. Delivered at TED conferences. To bring about the future we want to see. around the world. To understand who we are. From those talks, we bring you speakers and ideas that will surprise you. You just don't know what you're going to find. Challenge you.

0:40We truly have to ask ourselves, like, why is it noteworthy? And even change you. I literally feel like I'm a different person. Yes. Do you feel that way? Ideas worth spreading. From TED and NPR. I'm Manoush Zomorodi. Today on the show, ideas about addiction and moderation. I think moderation is so important. There are so many things in life that we want a little of, maybe quite a bit of, but not too much of. And, you know, Aristotle obviously had this insight many centuries ago. This is Dhruv Kular. He is a physician at Weill Cornell Medical College. And he would love his patience to live by Aristotle's famous words, it is best to rise from life as from a banquet, neither thirsty nor drunken.

1:32But in the modern era? Our world is kind of designed for too much these days. It's just inundated with content and food and desire and all sorts of things. For some people, just having access to all these earthly delights makes moderation impossible. Take a woman named Mary, for example. I met Mary last year. She's a middle-aged woman, and she has been struggling with alcohol addiction for decades. She told me that she started drinking when she was 18 years old, and soon after she could drink something like 18 beers in the sitting and barely even seem buzzed. And Mary tried all sorts of things to try to cut back on her drinking.

2:16She entered Alcoholics Anonymous. She used a medication called Antabuse. She tried alcohol rehab. But none of them were effective. And she struggled with alcohol. And it started to really take a toll on many aspects of her life. Then, about a year ago, she was at a bar with a friend who usually also liked to drink a lot. But that evening, Mary noticed that her friend had barely touched her drink. And her friend told her that she started taking Ozempic. And now she could barely bring herself to drink more than two beers at a time. And Mary was really interested in this. She'd always thought of Ozempic as kind of a obesity medicine or a diabetes medicine.

2:56And she was wondering, you know, what did it have to do with drinking? And as it happened, the next day, she saw this advertisement on Facebook that there was a clinical trial nearby that was studying whether Ozempic or semaglutide could help people with alcohol addiction. So Mary enrolls in the trial, and every week, the researchers blindfold her, and they inject her with the medication. It's either placebo, or it's semaglutide or ozempic. And within weeks, she notices that she doesn't really like to drink beer anymore. And this is something that she's been doing for decades. She switches to white wine, and then after that, she just stops drinking altogether.

3:35And what she told me was that ozempic really got rid of not just the food noise in her head, which is what a lot of people describe, but what happened for her was it took out alcohol noise. And so she had been ruminating about alcohol for most of her life, where to drink, how much to drink, how not to drink. And all of a sudden that seemed to vanish. And she told me that she could finally start to think about other things in her life because alcohol wasn't really an issue anymore. And she made a lot of changes. She started exercising. She really improved her diet. She'd been having marital problems for years and always kind of thought about whether to end that relationship and suddenly did when she started on Ozempic during this trial.

4:19You know, in Mary's case, she also experienced pretty significant reduction in her appetite. And so there were days where she was eating, you know, three, four, 500 calories a day. And she lost 55 pounds in just five months. Oh my gosh. And she ended up having to come off the medication because she lost so much weight so quickly. But, you know, she was able to maintain her sobriety afterwards. So even after she came off the medication, really, she's had a much healthier relationship with alcohol and she's maintained her lower weight, and she's maintained her healthier lifestyle. For her, it's been a really positive experience.

5:00I mean, she must feel like she's a completely different person in some ways. She does. I mean, it seems like I don't think she realized how much alcohol was driving a lot of her behavior and her thinking. And she was really able to, in a way, reinvent herself after she started on Ozempic. Nearly one in six Americans age 12 or older has a substance use disorder. We know addiction can be genetic, and yet shame still shapes how we talk about it. Now, a class of drugs, GLP-1s, promises to change how we understand and treat addiction. But is it really a silver bullet? Today on the show, ideas about the brain, addiction, and empathy, how medical breakthroughs are revealing more about how the mind responds to the modern world, but also why human traits like compassion still play an important role in helping yourself or others who may be struggling with addiction.

6:02So back to Dr. Dhruv Kular, who points out that it has been more than 20 years since the FDA last approved a medication for alcohol use disorder. GLP-1s give him, and many physicians hope, that a new era in treatment is just beginning. Stories like Mary's have led scientists to consider whether these medications could be helpful for all sorts of addictions, from alcohol and cocaine to gambling and compulsive shopping. Here's Dhruv on the TED stage. Research has found that GLP-1s might help people stop smoking, reduce their cravings for opioids, leads them to consume fewer drinks. As one neuroscientist put it, GLP-1s might be telling us that there's some type of universal pathology when it comes to addiction and that they are part of how we fix it.

6:56Now, that is a tantalizing prospect, that there's a general purpose key that unlocks the path to moderation. But that's what GLP-1s seem like they could be, moderation molecules. They don't extinguish our desires, but they help us keep them in check. And no one knows exactly why. One possibility is that they modulate what's called the brain's mesolimbic pathway, sometimes referred to as the reward system. Alcohol, nicotine, cocaine, social media, they all increase dopamine release in that pathway. And GLP-1s, they might be limiting the spikes of dopamine. So mice that are on the medications and given cocaine, they have smaller surges of dopamine, but they otherwise seem to maintain adequate amounts of the neurotransmitter.

7:47GLP-1s could be calming the water without draining the pool. I mean, I think for normal people hearing that get a shot of Ozempic and you can turn your life around, that seems amazing. But as a physician, what was it about these stories connecting GLP-1 medication to addiction that struck you as so, I mean, I guess strange and unprecedented? Well, I think you have to think back about the history of Ozempic. And it was first discovered many years ago. And glucagon-like peptide one, which is a naturally occurring hormone, I mean, that was discovered nearly half a century ago now. And it was always thought to have effects for diabetes and then later weight loss.

8:32But the idea that it could modulate the way that people were experiencing the rewards of drugs and other types of behaviors, that is a much more recent discovery. And so this kind of came about because there were just so many stories of people saying that they wanted to drink alcohol less. They didn't want to smoke as much. People who had been taking opioids weren't having the same types of cravings that they had in the past. And some Some of that you take as anecdotal evidence. You're not sure exactly what to make of it. But over the past year or two, there has been a good amount of trial work that has shown and is increasingly showing that there are pretty substantial effects here.

9:13And it may be that this class of medications will be an important adjunct to people who are struggling with addiction. But we knew that addiction was biological, right? I remember the shift in thinking like in the 90s, a flip that happened in terms of not blaming people who have addictions, but blaming sort of the way their brains work. What is different about this? And was that wrong? Well, I think, you know, there is still a lot of stigma around addiction. And so people who are struggling with addiction, I think there is a growing recognition that a lot of this is biological, that it's happening even unconsciously, and that people really struggle in ways that they shouldn't be blamed for what's happening here.

9:58But I think there's still a lot of stigma that's preventing people from coming forward when they have an addiction. We have, as you said, made a lot of strides towards recognizing how much of a biological process addiction is. And so we've known that for many decades. Now, what's interesting here is that GLP-1s, they seem to work for many types of addictions, or at least there's the promise that it's working across various types of addictions. So if you think about the medications we've traditionally had to treat opioid use disorder or alcohol use disorder or nicotine use disorder, those are all separate medications.

10:36And we think that there's a particular mechanism or pathway through which they're operating. Here, GLP-1s, they seem to be acting across these different types of addictions, which is quite novel and interesting. And the prior thinking had been that they are modulating mostly our desire for food and creating a sense of satiety. And now the thinking is that maybe these effects are much broader than we previously thought. So in addition, Drew, to being a doctor who sees patients, you do research and you write for The New Yorker magazine. And for that, you talk to scientists who are developing these drugs.

11:14Do they know exactly how they work? Some of the ways in which these medications are actually operating are still mysterious. And so, you know, one of the interesting things I came across in my reporting is that it's still kind of a question mark how exactly these medications are even affecting the brain. So, you know, as the medications have become these longer lasting, more powerful medications, It's not even clear exactly how or if they get into the brain. They're supposed to be, you know, in theory, too big to cross the blood-brain barrier, which kind of protects the brain from toxins or drugs or other substances.

11:52But what we're seeing from trials that are being published, not only on addiction, but on other types of disorders, they seem to have a number of positive effects. Yeah, I was just seeing that there's research into, like, the relationship between the gut and the brain as well, that it's not just the brain that these drugs affect when it comes to eating and addiction, but the conversation that's going on between the intestines and the brain? Yeah. I mean, for a long time, GLP-1s were thought to affect primarily the gut. You know, they have their receptors all over the body, their receptors in the pancreas and the gastrointestinal tract, the brain.

12:32Of course, GLP-1s, they stimulate the release of insulin. They slow the passage of food through the stomach. They're signaling to the brain that we are full. So there's a lot of crosstalk between the gut and the brain. And there's some thought that maybe some of what we're seeing, both in terms of addiction, but also other types of conditions, is related to the ways in which the medications are affecting both the gut as well as the brain. In a minute, more with Dr. Dhruv Kular on GLP-1s, how they're changing our ideas about addiction and why they don't work for everyone. Today on the show, the brain, addiction, and empathy.

13:14I'm Manoush Zomorodi, and you're listening to the TED Radio Hour from NPR. We'll be right back.

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15:37Check it out. Sign up at npr.org slash newsletters. It's the TED Radio Hour from NPR. I'm Manoush Zomorodi. Today on the show, the brain, addiction, and empathy. And if there's one class of drugs that has dominated the cultural conversation in the past few years, it's GLP-1s. There's a lot of buzz about weight loss drugs. Think about all the Ozempic and all that stuff. Oh, I love it. I love it. Let them know you've already tried diet and exercise. I didn't want to show up at another party and see all of my friends 20 pounds thinner and just be resentful. Ozempic, Wagovi, Munjaro. These are the brand names for drugs that were first approved to treat type 2 diabetes, but are also being prescribed for weight loss.

16:24And now researchers are studying if they're effective in other unexpected ways. They lower the incidence of cardiac events, even in people without diabetes. The possible brain health benefits of Wagovi and Ozempic can lower the risk of kidney failure, heart problems, stroke, and death. And as we heard earlier, one of the most promising uses for GLP-1s is treatment of addiction. But many physicians, including Dr. Dhruv Kular, warn that it isn't necessarily a cure for all. Like any drug, GLP-1s won't work for everyone. In fact, for some people, these so-called moderation molecules, they could have an alter ego as a desire dampener.

17:05Maybe some people lose interest in drugs or alcohol or food because they lose interest in pretty much everything, a condition known as anhedonia. It's also true that addiction is often a lifelong battle, but many people who start on a GLP-1, they come off it within months, whether because of side effects or costs or access. And even people who do manage to stay on the medications might ultimately develop a tolerance to them, such that their cravings for a drug ultimately return. And yet it is hard not to get excited about the potential for GLP-1s to treat addiction when you consider how little progress we have made.

17:50I mean, that's what's so, like, kind of bizarre to me, is that I feel like everyone was like, well, let's wait and see, like, a year ago, two years ago. And now, largely, the medical community has come around. But let's talk about, like, you know, everything has downsides. What are the downsides for GLP-1s as far as we know now? That's right. So I think the first is that it can be hard for a lot of people to stay on these medications. And that's going to be a problem whether you're taking this for diabetes or obesity or addiction. Of course, drugs only work if you take them. But at least in some studies, half or more of people come off these medications within a year of starting to take them.

18:35And so, of course, that is going to limit how effective they can be if people aren't able to stay on them. It's also possible that some people experience psychological side effects. There have been reports, not a lot of great research yet, but at least reports that people feel kind of a blunted mood or even anhedonia. They're not interested in doing the things that they used to do. you know, the cost is still a huge issue. And so, you know, there are a lot of efforts underway to make these drugs more accessible, more available to people, either through insurance or other programs that are going to mitigate the cost.

19:13But at least the sticker price can still be$1 ,000 or $1 ,300 a month. And so, as you can imagine, not a lot of people are going to be able to afford that. And finally, I would say, you know, side effects in terms of GI side effects. In clinical trials, they seem to be pretty well tolerated. So maybe 5 % or 10 % of people have, you know, significant enough GI side effects to come off them. But that is potentially higher in the real world and one reason that people are coming off the medications. And what about, like, long term? We just don't know, right? Like, some of the side effects may not show up for five years, a decade, 20 years?

19:53That's possible. You know, these medications have kind of blown up on social media and elsewhere over the past few years. But they have versions of these medications have been around for two decades now. So the first GLP-1 medication came out in 2005, 2006, Exanatide. And that had to be taken twice a day, and it didn't have as powerful effects on weight loss. And so it wasn't kind of the phenomenon that these newer GLP-1s have become. But there have been medications or versions of GLP-1s for two decades. And we haven't seen those really concerning side effects that have sometimes cropped up with other medications over the course of five or 10 years.

20:31And so I think that's not to say that these specific formulations couldn't have other types of side effects. But it does give me some confidence that what we're seeing here is likely to be a more positive story. I mean, that is reassuring in some ways. Like part of me is like, put me on it now, coach. You know what I mean? Like what? Why not? If it's going to prevent, you know, all the things that come with, you know, aging, right? Those inflammation based chronic diseases. But also, like, I heard something recently that gave me pause. So I was at an American Heart Association meeting and some researchers were talking about using GLP-1s preventively in populations of kids where they don't get enough exercise or eat proper food or just this idea that obesity and diabetes are hitting younger people at younger and younger ages, school-age children, that maybe if diabetes type 2 is rampant in a population, that this should be used preventively.

21:32And that kind of freaked me out. I mean, it was just an idea that was presented, but it sort of made me think like, oh man, are we once again going for the quick fix without trying to change and create better lives for people generally? I think that's a really important point, especially when it comes to children or adolescents. I mean, you know, it's one thing to commit someone who is in their 50s or 60s to a medication that they're going to need to take for the rest of their life. it's quite different when someone is 10 or 15 or 20 years old. And so I do think it raises a really important set of questions about the treatment model here.

22:09Is it really the case that people are going to have to be on these medications for the long term, or is there a way to use these GLP-1 medications as a bridge to other types of interventions? I think the other thing that this raises for me is that, of course, as you're saying, when a medication is so powerful, it becomes tempting to use it and to kind of not continue to push on the more societal factors that are creating the epidemic that we're in. You know, we're not potentially addressing or not addressing the root causes of obesity and diabetes and addiction. But it's also the case that we have been trying to do that for decades and not made a lot of progress.

23:02And so, you know, in the short term, we should consider how to get it to as many people as possible who could really benefit from them. Where does the conversation for personal responsibility and modulation and finding your own sort of balance between extremes. Where does that fit into this conversation? A lot of the challenges that we have, whether it's around our mental health or our physical health, is trying to bring ourselves into greater harmony with our environment. And for some people, that will require medications. For some people, that'll require social supports, therapy. But I think getting to this place where we recognize that moderation is important, but that the modern world is one that facilitates too much is a really important kind of frame shift just to think about, you know, how we should be engaging with all the delights around us.

24:01I mean, with all of this, as you point out in your talk, it makes us rethink sort of assumptions we've made about people's morals or their personality for centuries, that someone is weak-willed or has no discipline, that they can't stop themselves from whatever, drinking, smoking, et cetera. Do you think that we're being set up for a new chapter, a new way of thinking about addiction and the way we talk about or treat people who struggle? I think so. I mean, I think because these medications are so widely used, I mean, some of the estimates are that one in every seven, one in every eight people in the United States have been on a GLP-1 medication at some point.

24:49So these are millions, tens of millions of people who are using these medications and are seeing the effects of them in their lives. You know, so I think there's going to be a different relationship both towards obesity as well as addiction. And for me, some of this really came home during my reporting for this piece. You know, I underwent an MRI scan. They were showing me photographs of all sorts of things, whether it's Big Macs or, you know, mountains or alcohol like beer, wine, whiskey. And they were basically seeing how my brain reacted to these various images. And afterwards, they showed me, you know, in response to photographs of alcohol, there was very little activity in kind of the relevant centers of my brain.

25:33And they compared them to people who are struggling with alcohol use disorder. And those areas just lit up in those people. And for me, it kind of drove home this point that so much of our behaviors downstream of these processes that are happening inside of our brains before we even have an opportunity to make a kind of a reasoned decision about what we're going to do. And so I don't want to say that our behavior, our will has no role in these conditions. Of course, we need to encourage and help people make decisions that are in line with their health. But I think that needs to be paired with an understanding that a lot of these processes are neurobiological.

26:13And shaming people because they have these conditions is not going to be a productive way to go about it. That was Dr. Dhruv Kular. He is a physician at Weill Cornell Medicine in New York City, a health policy researcher, and a writer for The New Yorker magazine. You can see his full talk at TED.com.

26:36So what about those who have experience either being addicted themselves or helping people rebuild their lives after addiction? What do they think about GLP-1s and their potential to help treat this serious problem? Some people tend to take something like that and just run it out to the end. This is going to be the cure of addiction. I'm always like, well, settle down. Like, it's a useful tool. I think GLP ones hold an enormous amount of promise. But I do not think that there is a silver bullet for addiction, nor will there be one. This is Eric Zimmer. He's the host of the podcast The One You Feed and author of the book How a Little Becomes a Lot, The Art of Small Changes for a More Meaningful Life.

27:2530 years ago, Eric was addicted to heroin. And he warns us of looking for quick fixes. Because while GLP-1s may reduce cravings, addiction, he says, it contains multitudes. You see a lot of people who are depressed have addiction and vice versa. My experience with addiction or my battles with depression is that it's a bunch of different tools put together in the right combination, the right puzzle gets aligned that is what allows us to get over addiction, to deal with depression better, to make changes in our lives. All of those things I think of as a puzzle. And a puzzle isn't one piece. It's a lot of pieces.

28:07Today, Eric coaches people to rebuild their lives in ways that can make it easier for them to be in recovery. And much of his credibility in this community is built on his openness in discussing his own experience with addiction. Like many people, I started experimenting with drugs and alcohol as a teenager, and it was great for a while. I mean, I loved it. It was a real answer to the things that troubled me and bothered me. And as we know with addiction, as that goes on, that ratio starts to change. The enjoyment to problem ratio starts to change. And that's where most people who aren't an addict start to get off the train because they're like, all right, this really isn't worth it.