The Evidence on Ozempic to Treat Addiction

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2:14This is the New Yorker Radio Hour. I'm David Remnick. It's rare that a drug has had as big an impact on our lives as Ozempic. It's been on the market for a relatively short time, and something like 12 % of Americans have taken Ozempic or one of the others in its class, the GLP-1 drugs. Now, 12 % is a lot. But when you consider that around 40 % of us are obese, we're probably not at the plateau for GLP-1 drugs. And because these are relatively new drugs, there's a lot that scientists don't know about them yet. Dhruv Kular is a contributing writer covering medicine and health care. And he just published a piece of reporting in The New Yorker called Can Ozempic Cure Addiction?

3:02This segment will be called Everyone's Doing It, Doing It, Doing It. Are you willing to admit it's a wonder drug? I don't know about a wonder drug, but it's the closest thing we have. So how did you get clued into this research on GLP-1 drugs, Ozempic, Wigovia, and so many others, and then tie it to the problem of addiction? Yeah. Well, I've been interested in these drugs forever, in part because we saw, I mean, they can manage diabetes and then obesity, but not just that. I mean, it's not just an aesthetic thing with these drugs. So if you think about cardiovascular risk, stroke risk, chronic kidney disease, liver disease, all these things seem to be getting better the longer that people are on these drugs.

3:49And then there's just all these stories, these anecdotes from people who start taking the drugs. They don't feel like drinking anymore. They don't feel like smoking. They're not doing opioids. They don't want to gamble. They don't want to shop. And so there's an avalanche of these stories. And then you start to get these clinical trials. And that's what's trying to unpack, you know, is this something that's actually true and happening or is it just on Instagram? Well, how long have these drugs been around? Because to the average person, they started hearing about them, you know, a couple of years ago and through Hollywood and gossip magazines and who's lost 50 pounds and so on.

4:23But they've been in your life as a physician for how long? More than 20 years. So people don't realize this, but the first GLP-1 on market came about in 2005 and you had to take it twice a day. And then there were the next generation, about five— And people were taking it mainly for diabetes. Only for diabetes, basically. The next generation is about five, seven years later. You get drugs that you can take once a day. And then the real big shift happens when scientists tinker with these molecules, and they last in your body for a week or more. And that's when you start seeing these huge amounts of weight loss, that people are just losing weight as they start to take these medications.

5:01And so that kind of happened around 2017, 2018. And then a few years later, it kind of blows up on social media. And that's where it becomes a global phenomenon. Everyone is talking about these drugs. Everyone wants to be on these drugs. And when did it become apparent that it had this really marked effect on addiction? Well, so it's still becoming apparent. It's not 100 % clear cut that that's the case. But, you know, when basically drugs are approved based on studies of several hundred carefully selected individuals. And there's only so much information you can get when you study a few hundred people who are all healthy and don't have comorbidities.

5:43And that's how you get a drug approved. And now we're in the midst of this massive social experiment where tens of millions of people are taking these medications. patients and so all sorts of things are happening and people are responding to them in all sorts of ways and amidst that kind of explosion of uh use we're seeing more and more people reporting hey i don't feel like drinking i don't feel like smoking um and it seems to be doing something more fundamental than slowing down food in your gi tract or controlling your blood sugar but really playing with the reward system in your brain well people i hear people i know who take this for weight loss say the following to me, I hear less food noise in my brain.

6:27What does that mean? Well, it means that they're ruminating less on food. They're having fewer of these intrusive, repetitive thoughts about wanting to eat food, thinking about food, when's my next meal, all those things people have reported with food. And they're increasingly reporting that with alcohol or with cocaine or with any number of other potentially addictive behaviors and substances. And what seems to be happening is, you know, we've thought about these drugs as drugs that are affecting the body in the way of diabetes and obesity. But they are fundamentally or learning psychoactive drugs.

7:02They're playing with the reward system in the brain. And there are potentially huge benefits of that, but obvious drawbacks as well. What are the drawbacks? Well, you know, some people who take these drugs report loss of not just desire for food or alcohol, but loss of desire for pretty much everything. And so you have this phenomenon of what's called anhedonia. So what kind of pleasures are we talking? Are we talking about sex or hunger? So, yes, sex. You know, I spoke to a woman for this piece that loved gardening. That was one of the joys of her life. And she bought these beautiful Japanese maple trees to plant, and she just watched them with her in her backyard.

7:42She eventually closed the windows because she didn't want to look at her. Because she was taking Ozempic. Because she started taking Ozempic. Are we sure it's because she was taking Ozempic? Well, you can never be sure, but at least in her experience, she stopped taking it and her mood got better. And she felt excited to live in the way that she was before. You know, there are people on Reddit, patients I've spoken to who have reported, you know, in a minority of cases. I don't want to oversell this, but it is the case that some people, for somewhat unknown and mysterious reasons, experience the negative impact of these medications.

8:14People have started talking about them broadly as moderation molecules. They help you moderate, you know, your desire for all sorts of potential vices. But at the same time, for some people, they go too far. They turn into desire dampeners where everything that you enjoyed doing in the past, you have more and more difficulty enjoying those things. Well, explain the science of this. What molecule is it working on? I didn't know that there was a desire molecule that ranged from ice cream to sex to cocaine. Yeah. Yeah. So primarily, so the traditional telling of the molecule, GLP-1, it's a tiny molecule in your body that dissolves within minutes.

8:54That's what happens in our body normally. And what it does is a few main things. It attaches to receptors in your pancreas. It gets you to secrete insulin. It attaches to receptors in your GI tract. It slows down the stomach. And then there are receptors in the brain. And what it does there is helps increase the sense of satiety. But as we're learning more about the molecules, and as we've transformed them from lasting for just a few minutes in the body to hours and then days, we're seeing more and more potent effects. And again, bear with me for a second, but, you know, we're getting to this place where we're understanding that they're modulating what's called the mesolympic pathway, which is sometimes called the brain's reward system.

9:34And when you're doing that, what it seems to be doing is a few things. And some of this is in animal studies, some of it is in human studies. But it's lowering the kind of dopamine spikes that we receive from checking social media or from cocaine use or compulsive shopping, you know, you name it. But it seems to be doing that without draining the baseline levels of dopamine. So you can imagine just getting rid of dopamine altogether and turning you into a listless person who can't do anything. It doesn't seem to be doing that. What it seems to be doing is just calming the waters, which is why we see people don't receive as much of a hit or desire to use some of these things.

10:10If I take Ozempic, I'm going to stop looking at my phone every 13 seconds, too? Well, I don't want to make that claim just yet. But it's not out of the realm of possibility that people who take Ozempic, because, you know, it's operating on the same reward pathway. You know, you do have a dopamine hit in that area when you check your social media feed. I think that's a totally reasonable thing to study, see how people's social media use is affected when they start Ozempic. Are drug and alcohol rehabilitation centers using Ozempic now in a concerted way? There are some cases of rehab centers starting to use it, but I would say that the science is not there yet.

10:49We're just starting to get randomized control data. And that takes time. That takes time, exactly. And, you know, you start with the animal models and then a few dozen people, and now there are hundreds of people being enrolled in these trials. And I would want to wait for the readout of those trials to understand, are these actually in a systematic way helping people? But I have to say, you know, over the course of my reporting, I became more and more bullish on the idea that these are actually going to be really important molecules for the treatment of addiction. Now, Dhruv, what are your cautionary signals that you want to send about this new research?

11:26There's often a concern in medical reporting that drug makers amplify or exaggerate what they consider to be the good news. Are you concerned about that? Well, in this case, drug makers have not been focused enough on addiction. In fact, a lot of this research is not being driven by the drug makers, whether it's Eli Lilly or Novo Nordis. These are independent researchers in many cases that are hearing the stories of patients and trying to set up clinical trials that are independently funded to try to understand, is this working for people in a rigorous way? And so I'm less concerned about the conflicts of interest for this specific indication than I usually am for many other types of medications.

12:08So I think a couple things that are important to note. We've talked about the idea that we don't have the right treatment model in place yet. We don't know when we should start these medications, how long people need to be on them. We don't know whether people will develop tolerance to these medications such that their cravings will return. The psychological effects, at least for some people, could be significant enough that they have to come off the medications. And I think most fundamentally, these drugs aren't doing anything to address the underlying root causes of addiction. for a lot of people that is stress and loneliness and trauma and environmental factors that have put them in a position where they are using drugs as a coping strategy.

12:52And I think GLP-1s can give you a break. They can provide an opportunity to reset some things in your life, but they're not going to be a comprehensive response. I'm speaking with Dhruv Kular. More in a moment.

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14:22What are the politics around GLP-1s? RFK Jr., we know, is putting a lot of emphasis on ultra-processed foods, and he's critical of the pharma industry. Kennedy said in the past, quote, you could give every American three meals a day of organic food and diabetes would disappear overnight. So put the accuracy of that to one side for a moment. I mean, it does have a point about diet, sure. Does he have a point about medicating obesity instead of tackling the causes? Look, I'm all in favor of tackling the causes of obesity, changing the food environment, changing the built environment, getting people moving more, making sure that everyone has access to healthy food.

15:06I don't think anyone would disagree with any of that. The challenge is we haven't really been able to do those things for most people over the past half century while obesity rates have been skyrocketing. And so there's no argument about changing the underlying causes of obesity. But as we're doing that, this is a remarkable advance to help people in the immediate term as they, you know, they're struggling with all sorts of complications with obesity. to deny people access to that, I think, is totally wrongheaded. They're also a disciplining agent, right? Ice cream is delicious. Yes. Last time I looked.

15:42Yeah, yeah, yeah. Alcohol can be just swell. Yeah. And this acts as a disciplining agent in your life. Is there anything wrong with that? Well, as long as it doesn't go too far. What constitutes too far? What do you mean? If you're losing, if you lose pleasure in the things that you otherwise took pleasure in, which for many people includes a glass of wine or seeing your friends or gardening or going out and, you know, going for a run. If it starts to shave those things out of your life, that I think is the most fundamental potential risk. And, you know, in another way, you're using a chemical agent to change your desires.

16:28And so there are these kind of second-order desires that are affected as well. The first-order desire might be, you know, I want that cookie. And the second-order desire is I want not to have that cookie. So, you know, I talked to one woman who had been having marital problems for years. She started on this medication, and within months, she left her partner. And for most people— Because she said, I had been kind of inhibited by this alcohol noise in my mind. It had been taking up so much energy that I wasn't able to do what I wanted to do, which was ultimately, you know, start afresh. And this gave her the space to do that.

17:06In her case, it seemed like it was the right thing, but you could envision people making decisions that are less productive when they're, you know, chemically, when a substance is changing their desires in a certain way. How have obesity rates in this country been affected by these drugs? I'll say for the first time in the last four decades, we're seeing a plateau and even a decline in obesity rates. I don't think that's by dint of willpower. I think that has something to do with what's happening here with GLP-1 medications. And I think the hope is that over time, as more and more people have access to medications, but also as their newer and newer agents, ones that are just pills instead of injections.

17:49Different medications will hit different receptors, have different side effect profiles. I think, you know, I've written in the past that these are potentially some of the most powerful medications in the annals of chronic disease. We have not had a medication in the past that has allowed people to lose weight in the way that these medications do. Is access a matter of class? So far, it is certainly powerfully affected by class. I think that will change over time as there's more and more competitors in the market as public programs like Medicare and Medicaid potentially start to cover these medications.

18:25They're not covered now? Not for the indication of obesity. I mean, Medicaid is state by state, but for Medicare, you can't get it just for obesity. You have to have a secondary issue, whether it's diabetes or something else. What are the downsides of these drugs that you're hearing about, other than the anhedonia that they might produce? Well, you know, there are, in mouse models at least, potential risks for certain types of cancer. And so people with thyroid, a history of thyroid cancer, people have experienced pancreatitis, which is inflammation of the pancreas. And people continue to experience significant, in some cases, nausea, vomiting, and even anorexia.

19:01The other thing that I should mention here is that when people lose weight, they're also losing muscle. And that's particularly problematic for older people who struggle with frailty and not having enough muscle mass. And so it's important as people are losing this weight that they engage in, you know, an exercise regimen, strength training, and potentially increasing protein intake. If you were overweight, you're not, but if you were overweight, would you take these drugs? Absolutely. You would? Yeah. If I could tolerate them, if I wasn't having significant psychological side effects or nausea or vomiting, I think not just for the purposes of losing weight but for reducing the risk of obesity-related complications, I think it's something that anyone in that position should consider.

19:48Now, I've got to go off topic for a second here, Drew, but I think our listeners want to know this. You're a practicing doctor in a big hospital in New York City, in addition to, of course, being a brilliant writer for The New Yorker. And you just published an essay in The New Yorker called What the Pit Taught Me About Being a Doctor, The Pit obviously being a huge show on HBO. What does this show get right about your world? I think that over the past decade, I've tried to communicate the challenges that clinicians, doctors, nurses face when trying to deliver care in this system. That is everything from administrative burdens and quality measurement and the electronic health record and climate change and artificial intelligence, you name it.

20:35And somehow, this show has incorporated all of that and turned it into really good TV. It's like they have imbibed all the important conversations in healthcare and now put it into a compelling narrative that people want to watch. It is accurate. It is entertaining. It captures what is so hard and also what is so beautiful about practicing medicine in the 21st century. And for me, it drove home this point that there are all these challenges with the system and there always will be, but there is always room for grace. Thanks so much, Dhruv. Thanks for having me. You can find Dhruv Kular writing about the new OZEMPIC research, changes at the CDC, and much, much more at newyorker.com.

21:25And of course, you can subscribe to The New Yorker there as well, newyorker.com. I'm David Remnick. Thanks for joining us today. See you next time.

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