← Thriving with Addiction with Dr. Jonathan Avery
Thriving with Addiction with Dr. Jonathan Avery
Can Ozempic Treat Addiction? GLP-1s and the Future of Medicine
00:32:23
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- [00:00]
A
Welcome to the Thriving With Addiction podcast, where we explore how recovery is not just about surviving, but about truly living. Each week we'll dive into the science stories and strategies that help people and families heal from addiction and build healthier, more resilient lives. I'm your host, Dr. John Avery. Let's get started. I'm John Avery, and welcome back to Thriving with Addiction. Today I'm joined by Dhruv Kullar. Dhruv is a physician and associate professor of health policy and economics at Weill Cornell Medical College, where he's one of my most trusted colleagues and a staff writer at the New Yorker, where he covers medicine, healthcare and politics. He serves as director of the Physicians foundation center for the Study of Physician Practice and Leadership and associate director of the Cornell Health Policy Center. His research on value based care, healthcare consolidation and medical innovation has been published in JAMA and the New England Journal of Medicine. He earned his MD from Yale, trained at Mass General Hospital and Harvard Medical School, and received an MPP from the Harvard Kennedy School. Dhruv, welcome.
- [01:12]
B
Thanks for having me. Great to be here.
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A
You have had such an interesting career doing things that span medicine to policy, to raise writing for the public. Tell me how you became the scholar that you are.
- [01:25]
B
Well, first of all, thanks for having me. It's such a pleasure to be able to do this. I feel very fortunate for the kind of varied nature of my career. In some ways it's just been an attempt to not get bored doing one thing for too long. And so as you mentioned, I'm currently a physician and I work as an internist at Weill Cornell and then an associate professor in the Department of Population Health Sciences, which is where I focus a lot of my work on healthcare policy research. So things like value based payment and Medicare Advantage and kind of the structure of the healthcare system and how that's changing and how changes in the structure of healthcare affect doctors and affect patients. And the final part of what I do is as a writer and so I write for the New Yorker and that's been a wonderful experience in terms of being able to follow interesting ideas, where they lead and try to understand what's happening today, but also what might be happening a few years from now and talking to people across the country about the future of healthcare. And so, you know, I feel very fortunate to have that type of blend in my career. And in some ways I always was striving towards that. And so, you know, I was a pre med in college and my dad's a doctor, so that's kind of a risk factor for going into medicine, of course. But I always had this sense as well that I wanted to practice medicine. I always wanted to be seeing patients as part of what I did. But I also really wanted to be thinking about the system around healthcare.
- [02:54]
A
And it seems like you were a writer from the beginning. If I'm not mistaken, you covered sports when you were in college, is that right?
- [03:00]
B
That's right, yeah. So I wrote for the Yale Daily News in college and was covering mostly sports at that time, you know, football, basketball, tennis, et cetera, and loved that and kind of got the bug in terms of writing and then, you know, did a lot of reading of great physician writers, people like Oliver Sacks and Atul Gawande and Siddhartha Mukherjee and people that I really looked up to. And in a way, they kind of made clear that that type of career was possible where you could be deeply engaged with patients, but also be speaking to broader audiences about both the beauty and the challenges of medicine.
- [03:39]
A
You're here to talk about one of the beautiful new innovations in medicine, the GLP medications. But before we hop into that, I was curious on some of your thoughts on medicine in general. You wrote a great piece for the New Yorker on the Gilded Age in medicine. You called it Walk Me through how while there's these innovations, there's some concerns overall. Is that right?
- [04:03]
B
Well, that piece was really motivated by, you know, what I think a lot of people, both clinicians and patients, feel is that the system is not working well for anyone. And part of the reason for that is that medicine has become more of a business over time. And part of part of that is, you know, there are corporate actors that are playing larger and larger roles in healthcare, but even nonprofit entities act more and more, like for profit systems. And so the article was trying to get at the myriad ways in which this type of profit first mentality has come to pervade medicine. And what are some of the things that we can do to try to push back against. Against that and keep kind of clinicians and patients at the heart of what medicine is about. And so, you know, I talk about things like private equity, acquisitions of physician practices, consolidation, both in the health insurance space, but also in the healthcare provider space. You know, some of the tactics that hospitals and others are using to extract payments from patients and deny patient's care in some cases. And so these are all really concerning trends, But I think over the past year or two, there is more of recognition of some of this activity. And there's legislation both at the federal level and in states across the country trying to address some of these issues,
- [05:29]
A
is that, do you think how change will happen at that level, or what can we all be doing in medicine to help improve things for our patients?
- [05:36]
B
Well, certainly part of it will take legislative action, but I think there's a lot of advocacy work to be done as well, and that might happen on the part. Part of patients and families, but I think it's really important for clinicians and doctors to speak out about what they're seeing and to try to play a hand in how to create a system that works better for everyone. And I think what always needs to be the focus there is how do we make sure that patients receive the highest quality care and that that care is affordable and accessible. And so I think if we keep that at the heart of the advocacy and the work that we are doing, you know, there'll be a lot of public support for the reforms that are needed.
- [06:19]
A
Right. Because I've heard some of the concern about the GLPs or other medical breakthroughs. Are they improving health or are they just increasing costs overall? And, you know, what are your thoughts on some of the way that medical breakthroughs interact with how the system's doing?
- [06:37]
B
Well, I think the first thing to say is that these drugs are an incredible innovation, and they have all sorts of applications that weren't initially even understood. And so I think for a long time, We've thought about GLP1 primarily as about managing diabetes. That was kind of the way in which they were initially conceived of and what they gained initial approval for. And over time, we're seeing, of course, effects on obesity. People can lose 15, 20, 25% of their body weight. But it's not just, you know, an aesthetic thing. This is something that really seems to be improving people's health in all sorts of ways. There are studies that have found improvements for kidney health and cardiovascular risk and stroke risk and fatty liver disease. And so alongside these types of, you know, better diabetes management and better weight management, there are commensary improvements in health outcomes. I know we'll talk a little bit about the emerging evidence on addiction as well. And these medications seem to have some potential there, which is what's really, I think, an exciting and unforeseen potential benefit. Yeah.
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A
Talk a little bit about GLPs in general. What medications are we referring to? How do they work? Tell me about a little bit more on the medical role before we jump into addiction.
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B
Sure. So, you know, primarily there are medications known as semaglutide, which hits 1 GLP1 receptor and then tirzepatide which hits 2 GLP1 and GIP. And these medications, you know, they have a number of functions in the body. They induce the pancreas to secrete more insulin, they slow the passage of food through the gastrointestinal tract, they help create a sense of satiety which makes people generally eat less. And so there are, and there's a lot of kind of emerging evidence that they may have anti inflammatory effects. And so some of the, for instance, cardiovascular benefits that we see, they actually happen even independent or before large amounts of weight loss. So it's not as if people are just losing a bunch of weight and then their cardiovascular weight, their cardiovascular health improves. It's the case that there's possibly anti inflammatory effects that are leading to better, you know, neurologic health and cardiovascular health, even independent of the weight loss. And so they've really become a little bit of everything drugs in a way. And I think, you know, there's always a risk of overstating what, what, what these medications can do because they seem to be doing so many things effectively. But I do think that they are one of the greatest advances in the annals of chronic disease.
- [09:23]
A
Should it be in the drinking water? I mean, are there, are there any concerns? I know that as many people that try them, about half the people discontinue them by, by a year. Is that right? What are some of the side effects or some of the things that get in the way of these benefits?
- [09:37]
B
Yeah, we should definitely talk about that. So many people come off these medications within a year of starting them and the estimates vary. But as you said, half and sometimes even 2/3 of people in some studies come off these medications. It's not always clear exactly why that's happening. One reason is probably side effects. So many people experience gastrointestinal side effects on these medications. In the clinical trials they've been reasonably well tolerated. Maybe 5 to 10% of people have to come off for GI side effects. But in the real world, for whatever reason, maybe it's more people are taking them. The types of people who are taking them are not exactly the type of people who are in the clinical trials, but many more people seem to come off the medications. There's also of course the issue of access and cost. I mean there have been GLP1 drug shortages for the past few years. That's starting to improve as of the past year or so, but also cost. And so these medications can retail for $1,000, $1,300 per month. That's not to say everyone necessarily pays the sticker price. But they are very expensive medications, and in many cases, insurers will not cover them purely for the indication of weight loss. They may be covered for diabetes, let's say, but not for weight loss or some of these other indications yet. And so while they are, I think, a substantial advance in the right direction, making sure that people have access to these medications is not the same thing as the medications themselves being very effective. I'll just note that we've had situations like this in the past. I mean, hepatitis C drugs, the new generation of hepatitis C drugs that came out about 10 or 15 years ago now, they are incredibly effective at curing hepatitis C in a way that prior treatments were not able to do at all. And you would think that everyone in the US who has hepatitis C should have a chance to be on this. But something like two thirds of people who are in theory eligible to take hepatitis C medications have not received them. And so this is a enormous problem, not just with GLP1 medications, but with potentially helpful medications of all sorts.
- [11:49]
A
And in terms of improving access, a lot of my patients are now getting them delivered sort of directly from these companies. I think they're startups or different types of companies that are shipping them in the mail. And you see the doctor virtually. How does that type of delivery, do you think match up with our current healthcare system? What are your thoughts on that?
- [12:11]
B
Well, I think people are turning to alternate sources for access. A lot of, as you're hinting at, direct to consumer companies are now providing GLP1 medications and other types of medications. Some of that reflects challenges that people have accessing healthcare through traditional means. And so it's not surprising to me that people will turn to alternate sources to receive medications that they feel that they need. I think that can be to the positive. But one of the concerns that I have is there is not always a relationship that is built with a clinician at those settings of care. And that may actually contribute to some of the challenges that we're seeing in terms of adherence over time, or managing side effects, or dealing with some of the issues that arise when you're taking a powerful new medication. And so I think to the extent that they can help expand access and maybe even reduce cost, in some ways, I think that's a positive. But where I get concerned is when it's more of a transactional relationship in which people receive care or the medication largely unsupervised, they receive a kind of a vial of syringes and some of the medication and check in every now and then. That is not the same as having someone whose care you are under who's able to help you through the challenges that might arise along the way.
- [13:33]
A
Right. Because in addition to some of the side effects you've mentioned, there is the risk of going on and off this, this medication. And I've seen people from obesity, and we'll talk about addiction in a second, that either they lose access or side effects and they end up in a, in a state that's sort of unsupervised and a bit erratic because of some of this access issue.
- [13:53]
B
Right. And we don't know the effects of going on and off a medication like this certainly. And we don't know you other people are doing what's called microdosing, taking these medications at lower dosages in an attempt to extract some of the benefits without some of the side effects or if they want to lose a little bit of weight. We have not studied those things in detail and it's not clear what the long term effects are going to be. I will just also mention on the idea of kind of yo yoing on these medications where you start, you stop them, start and stop them. You know, a lot of the health effects, not just diabetes management, but obesity management, but the rest of it, they reverse for many people if you come off the medication. Some people might lose 10 or 20, 30 pounds and then come off the medication. And within a year they may be close to where they started. And so one of the challenges of these medications, which is true of many chronic medications that you need to take, but particularly with a medication like this, is that the benefits seem to dissolve if you're not taking the medication any longer.
- [14:55]
A
Right now those are all key points and sets us up to discuss your article and the role that these GLPs pay for addiction. You wrote this great article, can Ozembic Cure Addiction? For the New Yorker. Let's dive into it. First off, I really like the way you define addiction. You define it sort of in a couple, you highlight a couple aspects of addiction in your article. You certainly talk about it being rooted in neurobiology, but you talk about it as a battle between first order and second order desires. You talk about opponent process theory. Some of these things we don't talk about actually as regularly in the field of addiction as as we should. Do you mind discussing some of your thoughts on addiction because it relates to how we're using GLPs?
- [15:36]
B
Absolutely. So the first order and second order desire, I think most People that's kind of a fancy way to talk about something that most people probably intuitively grasp. A first order desire is kind of the immediate thing that you're thinking. So if you see a cookie in front of you or a drink in front of you, maybe for a lot of people the first order desire is just to have it, something delicious is right in front of you, grab it. The second order desire may be more complex. It's, you know, maybe you are trying to watch your weight and so at some level you really don't want to have the cookie or you don't even want to want the cookie. Similarly, people who struggle with substance use disorder, you know, in the moment they may feel like, you know, it's something that they, they really want, but, but deep down or at another level, they, they want to maintain sobriety. And so that is a battle that I think GLP1's kind of in an interesting way end up playing into. The other theory that, that you noted is kind of this idea of opponent process theory, which has been kind of circulating for, for more than half a century now. And it's kind of this idea that the body ends up balancing the high of a drug, the initial high of the drug with an opposing kind of come down or a withdrawal. And over time the, the withdrawal or the kind of desire to stave off that type of withdrawal or negative affect that comes from not having the drug grow stronger and stronger. And that's why people keep returning to the, the, the, the drug that they're taking. The other thing that I thought was quite interesting, and this came from some of the scientists that I spoke to in this study, was, was this idea of a difference between wanting something and being motivated to do something. And so the wants and motivations are actually two separate things, although, you know, colloquially we might talk about them as the same thing. So it's possible not to even like something anymore and still feel the urge to do it or want it. Many people might feel this way about social media. You may not have, get a lot of happiness or joy from using social media, but because there's this kind of loop in your mind or that you feel like you need to do it, or there's a kind of aversive sense by not doing it, you keep returning to the thing. And so, so this idea between wants and motivations, separating those two out, I thought was also a useful framing.
- [17:58]
A
Yeah, no, it's so key and it's what we see clinically in addiction is, I mean, people imagine people seeking pleasure all the time. And we talk a lot about the reward pathway being activated by these substances. But a lot of what propels the use forward is starting off withdrawal, trying to feel normal, not even wanting it, but sort of needing it to just survive. And that's a really tough place to be for a lot of folks. And I think having the GLPs as another option helps us think about it even more. So as not a moral failing too, right? These are really complex things in our brain. Like, one of the great things about the GLP for obesity is that it sort of further highlighted that it's a medical issue, not a moral failing. And I think also they reinforce that for addiction that there are these things that can really help with these complex brain processes. And GLPs, I think, might uniquely target some of these brain areas that are responsible for some of this.
- [18:50]
B
Right, Exactly. You know, one of the things that I found so interesting is that, you know, scientists aren't exactly sure how or whether GLP1s even get into the brain. So, as you know, you know, the GLP1 or the brain has a blood brain barrier where it's supposed to keep out toxins and medications and pathogens. And as the GLP1 medications have gotten bigger over time, they seem to be, or they should be, kind of too large to easily cross the blood brain barrier. But clearly they're having effects inside the brain. There's lots of theories about how that might be. Maybe they stimulate the vagus nerve, maybe they go in through small areas that are relatively less well protected by the blood brain barrier. Maybe they hitch a ride along with, you know, other proteins that are that are circulating. And so there's a lot that we don't understand yet about how exactly these medications seem to be modulating some of the reward pathways in the brain. One area that seems to be implicated is the mesolimbic pathway, which, as you know, is a place where there's a lot of dopamine signaling, particularly in response to things like alcohol or nicotine or cocaine or social media gambling. All these things seem to increase dopamine release in the pathway. And at least in animal studies, it seems that GLP1s may be limiting the spikes of dopamine in response to some of those substances. So, for instance, mice that are on the medications and given cocaine, they have less of a surge in dopamine, but they otherwise seem to maintain adequate amounts of the neurotransmitter. And so it's possible that part of what GLP1s are doing are mitigating some of the immediate hit that you get in response to some of these things. One thing that I want to point out that is a significant concern and was something that came up with some of the patients that I spoke to in the story was that there's also a risk when you're modulating the reward pathway, that there are spillover effects or there are unintended consequences for pleasure or motivation more broadly. And so some patients I spoke to experienced anhedonia on the medications. You know, I spoke to a woman who loved gardening. You know, that was one of the joys of her life. And after she started on the medication, she basically totally didn't want to do it anymore. So she had bought these Japanese maple plants. She wanted to plant them, and they ended up just withering in her backyard. And she closed the windows. I looked out onto the backyard because she couldn't bear to look at it. And she ended up coming off the medications for that reason. And at least, you know, according to, you know, what she told me, her mood seemed to improve. And so, again, I don't want to present GLP1s as a panacea, but I do think that they're in a very promising potential remedy, and some of the studies are starting to bear that out right now.
- [21:45]
A
There are side effects, as you were saying, there's physical side effects. Some patients can't tolerate it. They're nauseous. They're, you know, they lose too much weight, and they can't stay on it. I've seen people for addiction just as you described. They take it and it sort of blunts other rewards, makes people even feel a little depressed or sort of uncomfortable in their own skin. Tell us some of the data, though, that says that maybe we should try this especially for alcohol.
- [22:08]
B
Yeah, absolutely. So, you know, one of the studies that I, you know, went to see was out in Denver at the University of Colorado, and they were this researcher named Joseph Schacht. He had enrolled, you know, around 50 people in a clinical trial that was his randomized trial that was trying to understand whether an oral version of semaglutide could reduce people's. The number of beverages, alcoholic beverages, they had, if they had significant alcohol use disorder. And they did a number of things. I mean, they put people through MRIs, and they put people through cue reactivity tests where they have them, you know, bring a drink to their, you know, to their nose and, and smell it and put it back down and rate how, how much their. How strong their desire to have that drink was, and then they track people's drinking over the time that they were in the study. And the results, you know, they're currently under review, but he shared some with me, and they were pretty striking. Um, and. And so, basically, participants before they entered the study were drinking something like seven drinks a day. And after two months on semaglutide, they about half as much. The number of days on which they were drinking heavily, which was kind of four or more drinks for a woman or five or more drinks for a man, fell from 2/3 to a quarter. I talked to some patients in the study, and they said things like their emotional response to alcohol was reduced. And interestingly, it didn't seem to make people any more likely to become abstinent. It wasn't as if people weren't drinking at all, but they were drinking half as much or 3/4 less than they did before. And, you know, Shock told me that, you know, that at least his experience is one of the goals for some of his patients. Some of them don't want to be totally abstinent. Some people want to drink like a quote, unquote, normal person is the way that they put it. And so these medications, they have different effects for different people. But the trial seemed to be pretty striking in terms of the results. And this is consistent with some other research that has been coming out. You know, there was another study that was published last year that had similar results in people who weren't necessarily trying to reduce their alcohol consumption, but ended up doing it as a byproduct of being on these medications. There's observational data that has found similar things, not just for alcohol, but also for opioid use disorder and the risk of opioid overdose. And I think that in the coming months, in the next year or two, we're going to see a lot more trials that are published, and I think at least some of them will come back positive.
- [24:44]
A
And that includes for behavioral addictions, too.
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B
You know, I think the evidence on that is. Is less well developed. I think for alcohol use disorder and to a lesser extent, opioid use disorder, there is a stronger and emerging body of evidence. I think people are starting to look into things like gambling or compulsive shopping. There's certainly a lot of anecdotal evidence that people seem to have less desire to do those things. But I haven't followed closely whether or not there are kind of randomized trials that have started testing those two things specifically.
- [25:19]
A
Right. But back to alcohol, I think, you know, over the last 10, 15 years, there's been this shift in addiction treatment, led in part by naltrexone, which is also sort of can be a moderation medication, which is the idea that to be in recovery doesn't necessarily mean you're abstinent from drinking, even if you had a severe problem. And, you know, meds like naltrexone and now the GLPs are one way to potentially moderate successfully. And that's very different than historically what we would tell patients when they came to office. We would say, you've got to be abstinent and go to aa. It's interesting that these meds can create different outcomes.
- [25:57]
B
Absolutely. And I think this speaks to the idea that for different people, there may be different paths to having a healthier relationship with some of these substances. So for some people, it may actually still be the case that total abstinence is. Is the right thing for them. And of course, that is one of the dominant paradigms with Alcoholics Anonymous. But for. For other people, that may not be the best path, and it may not be the most sustainable path. And what is exciting about the potential for GLP1s is that folks might now have different options in terms of how they want to go about achieving a healthier relationship with alcohol or any number of other behaviors or substances.
- [26:38]
A
Right. And so if someone's coming to me for treatment now, I struggle a little bit with who I should recommend a GLP medication for. I mean, you mentioned that a lot of people in the opiate youth study were thin to start. That's some of the people they're experimenting on. And that's what I run into often. If I can get it for another indication they have diabetes or obesity and they're drinking too much or using substances, then it's sort of like, let's give it a try. Especially other things haven't worked, but it's. Everyone wants to try it these days, and there's some risk if, you know, especially as I've seen people's weight go down and things like that. What do you suggest to people that are maybe interested but unsure if they qualify or what some of the unintended side effects may be?
- [27:21]
B
Yeah. So, you know, I'm not sure that we're quite at the place where this is being used broadly in clinical practice, where someone has kind of an isolated substance use disorder and you want to. Want to start this medication. But I was surprised to learn that, you know, initially a lot of this research was done in people who had a BMI of 25 or higher. You know, for the reasons that you talked about. But increasingly, even people are at lower BMIs. 23, even 20 are in these studies, and they seem to tolerate the medication reasonably well. Of course, people are monitoring whether they fall below a certain safe weight. But I was surprised to learn that a lot of these studies actually enroll people who are at lower vmis. And that seems to have worked out okay. Maybe they don't lose as much weight as someone who starts at a higher weight would. You know, I think one of the questions in my mind is of course about adherence, you know, whether of course, addiction is often a lifelong struggle for a lot of people. And if you're coming on and off this, this medication, is that going to be a sustainable path towards, to, towards a healthier relationship? But there's also this open question that some scientists have raised is, you know, do you develop some type of tolerance to the medication such that cravings return over time? You know, maybe a lot of the decrease in cravings for alcohol or drugs coincides with the decrease in cravings for food that you have particularly strongly in the first few months after starting the medication. But does that return over time? And we don't actually know the answer to that question yet. A lot of these studies follow people for two months, three months, maybe up to six months, but certainly not over the course of years. And so I think that's still an area in which I think we need more research to figure out what exactly the long term effects will be.
- [29:13]
A
Yeah, that's a great point. We definitely need to follow more people over time. What I've, what I've noticed concerningly in, in a couple patients in terms of going on and off is I had a couple people I can think of that had never been hospitalized for alcohol use and had really good outcomes on the GLPs, and then couldn't get them, or they became too thin and they couldn't get prescribed anymore, who then had very spectacular relapses, more binging than they ever had before, ended up hospitalized when they'd never been hospitalized before. So I do think it is worthwhile, even if it feels like it's, it's helping to couple it with other behavioral changes or other ways to think about it, because I think there is that risk of, of what happens with time.
- [29:53]
B
Absolutely. And that's, you know, that's true, of course. You know, if you're using these medications for diabetes or weight loss or osteoarthritis or addiction, you know, I don't think they should be viewed as the sole intervention. They need to be kind of a pack part of a broader package or suite of intervent intervention, some of them behavioral, some of them potentially pharmacological, that are coming together to help people with their health in some way.
- [30:17]
A
Right. And you mentioned the hepatitis C treatment here. You mentioned Prozac in the article, which I think is a good analogy. Like, we thought no one would be depressed ever again when Prozac came out. And so accessible and so well tolerated. But of course, depression is complicated and you need to tackle it with all the other things you need to sustain wellness. Exercise and therapy, if needed, to understand things and diet and. And so it's just like with weight. It's true of addiction that you. It requires a whole bunch of interventions to sustain wellness.
- [30:47]
B
Right? Yeah, interventions, and of course, social supports and all the rest. I think, you know, Prozac was interesting because not only did its reputation kind of outpace some of the evidence of its benefit, but it kind of brought this narrative to the fore around the chemical imbalance of depression that. That, you know, has certainly been complicated over the decades since Prozac came out. And so, you know, it's possible that we'll find something similar with GLP1s. And anytime that you are using a medication that changes people's, you know, sensitivity to rewards or their behavior in some way, it's something that we need to, you know, undertake cautiously and monitor closely, as you know. And so while I'm very optimistic that these will be another tool in the toolbox for people who are receiving treatment for addiction, there's still a lot of unanswered questions that I think need to be studied in the coming years.
- [31:43]
A
Well, Dhruv, thank you for coming on today and sharing your thoughts and expertise around the GLPs and everything else in medicine. Keep doing all the great work that you're doing.
- [31:53]
B
Well, thank you so much. It's been great to chat with you.
- [31:56]
A
Thanks for listening to the Thriving with Addiction podcast. If you found today's episode helpful, please follow and subscribe wherever you listen to your podcasts and share it with someone who might benefit. You can also connect with me on Instagram, LinkedIn and YouTube or visit thrivingwithaddiction.com to learn more. Stay tuned for next week's episode and remember, thriving is possible.