The amount of overdose deaths in the U.S. is staggering. And while addiction is a disease, there’s no specific medical treatment or cure for it. Our guest this week points out that weight loss drugs and GLP-1s, or glucagon-like peptide-1s, which are used to treat type 2 diabetes and obesity, can be effective for helping people reduce cravings and consumption of drugs, alcohol and compulsive behaviors like gambling. Nick Reville is the cofounder and executive director of the Center for Addiction Science, Policy, and Research (CASPR). He joins WITHpod to discuss how he found his way into this research area, lessons learned from other health crises, innovations geared towards eliminating addictions at a widescale level and more.
Note: This is a rough transcript. Please excuse any typos.
Nicholas Reville: I think that the evidence that’s come out around cravings really creates this level of granularity, as you think about it, as the specificity where you say, okay, there can be all kinds of things that lead to a craving. So there could be depression, anxiety, some life disruption, trauma, all kinds of stuff that triggers a craving. Once you have some kind of a dependence on a drug, it can just be the use of the drug that leads to the craving. Some people, I think it’s biological. They have their first sip of alcohol and they’re like, this is it, this is my thing. Alcohol is my thing and they just can’t stop.
So there’s all kinds of things that can lead to cravings, but cravings I think are really a more specific and more helpful way to look at what’s happening in addiction. And if you reduce those cravings, you can give people a chance, some space in their lives to address the other patterns, the other circumstances that have led them in that direction.
Chris Hayes: Hello and welcome to “Why Is This Happening?” with me, your host Chris Hayes.
A 2020 congressional analysis found that the opioid crisis was costing the U.S. $1.5 trillion a year. That number is probably outdated by now. It’s a staggering amount of money, not to mention the tens of thousands of deaths from overdoses every year. This past year that we have data for, I think it was 2023, which is the first year we have data for, we saw overdose deaths come down for the first time in a bit. Part of that, I had Javier Becerra, who’s the Secretary of HHS outgoing. On the program he talked about a bunch of different things they’ve done at the federal level, trying to fund harm reduction programs, get naloxone into people’s communities. That’s a drug that you could use to interrupt overdoses.
There’s also been a change in the chemical composition of fentanyl, which is basically the fentanyl has gotten weaker in certain places or has been more diluted because of changes in the chemical supply. There’s a bunch of things. And it’s encouraging that we’ve seen reductions in this, but we’re still 3 or 4 or 5x what it was just a few years ago. I mean, the curve of overdose deaths and opioids in this country is like staggering and shocking. And that along with car crashes and alcohol related death are the huge part of what’s driving the fact that we are not seeing life extension in the country.
In fact, we saw a decline in life expectancy for a number of years. Now it’s sort of tick back up a little bit, but we’re not seeing the kinds of gains we should see. And it’s largely due to just a few things. And probably the biggest is addiction, underneath the umbrella of addiction. And yet if you think about addiction as a disease, which I think a lot of people understand it as and think of it as, it’s kind of weird that there’s just no treatment for it medically. Like there are addiction treatment programs. But you know, if you have diabetes, if you have high cholesterol, like I do, there are drugs you can take that reduce your risk significantly.
I’ve been on statins for a few years already, I’m only 45. There basically is nothing like that for addiction. And maybe it seems a little weird to think that there could be, but I remember 30 years ago, it seemed crazy there would be a cure for AIDS. I mean, that seemed way past out the frontier of the possible. And so there’s this new effort. It’s the brainchild of someone that I’ve happened to have known for a very long time. He’s a good friend of mine, full disclosure. It’s called the Center for Addiction Science Policy and Research. And what they’re committed to is trying to create the conditions under which we can have a kind of big swing cure for addiction. And what they’ve identified is that we are not really doing the kinds of things at the research level and in drug development that might even get us there.
There’s a whole bunch of policy apparatus to maybe have a kind of big swing cure for addiction as outlandishly blue sky and utopian as that sounds. And I was a little skeptical when I heard Nick first talk to me about this, but I’ve been reading policy papers they’ve been putting out. They’ve been raising money. They’ve been talking to all sorts of people. And I’ve been learning so much and I thought this would be a great conversation for the podcast. So Nick Reville is the co-founder and executive director of CASPR, the Center for Addiction Science, Policy and Research. He’s an old buddy of mine. Nick, welcome to the program.
Nicholas Reville: Hi, Chris. Nice to see you.
Chris Hayes: How you doing, Nick?
Nicholas Reville: I’m doing good.
Chris Hayes: What was your way into this problem question?
Nicholas Reville: So I live in Providence where you and I went to college. And I started about 15 years ago, I volunteered for a mentoring program at a nonprofit here that was sending folks into the juvenile prison in Rhode Island to help kids that had been put into prison as teenagers and try to support them in some way. I went in, I very naively thought that I would be able to make a big difference in a kid’s life right away.
And I met a guy whose name is also Nick and he was 15-years-old. And since then, I’ve been the only stable adult in his life for the past 15, 16 years. And both of his parents died from heroin when he was a kid. So his dad died first, his mother died when he was 10. He’s been in and out of prison since then. He’s had his own struggles with addiction. He’s overdosed and survived multiple times. He’s had babies with two different women, both of whom I knew well. Both of those women have since died of heroin. And it’s been just absolutely brutal.
And you’re actually catching me at an interesting time because yesterday afternoon, I picked him up at prison after three years in high security prison in Rhode Island. And he’s out again. And we’re going to try again for the, you know, I don’t know, seventh or eighth time to try to get him on a stable path, you know, building a stable life.
Chris Hayes: And was it the challenge of wrestling with this particular substance use disorder that kind of alerted you to have, because I know so many people —
Nicholas Reville: Yeah.
Chris Hayes: — and we’ve talked about in the program, I think probably everyone listening to this program has had an addict in their life, has had addictions themselves or had addicts, varying degrees of severity, substances that are more and less dangerous or more and less psychologically destabilizing. Obviously smoking, for instance, a really interesting one because it’s so unhealthy and terrible for your health, but it doesn’t like change your behavior.
Nicholas Reville: Yeah.
Chris Hayes: You can have a fully productive life. Drinking is in a different space. Opioids in a different space. And I think most people have had the just maddening feeling that this is such a hard problem to solve. And so many people have tried so many different ways and tried and failed. I feel like the first time you and I talked about this, it just never occurred to me that there could be a permanent solution or a medical solution. I think in my head —
Nicholas Reville: Yeah.
Chris Hayes: — it’s like, yeah, addiction is part of the human condition. It’s like we’re going to come up with a pill that makes everybody happy. It’s like, well, you can’t do that. We wrestle with the demons we wrestle with.
Nicholas Reville: Yeah. I mean, there’s so much to say here. There’s so much philosophy in this. But I think that for me, being with Nick along the way, trying to get him treatment. You know, there are medicines for opioid addiction like methadone, suboxone. They work very well while you’re taking them, but there’s lots of reasons why people don’t want to take them. Side effects, you know, restarting, you know, dependency on the drug after you’ve been off it, a lot of stigma, difficulty getting these things. Methadone has been a political football for 50, 60, 70 years. So just getting people access is difficult and you can spend your whole life driving in the morning to try to get methadone. And if you don’t have stable transportation, if you’re facing poverty, other situations, it can be very hard to be stable on medications that are highly restricted that you have to take on a daily basis.
Chris Hayes: In a specific place that you have to get to and go to multiple times a day perhaps.
Nicholas Reville: Yeah. So really, what we have now is not well suited to the actual condition that people are facing in many cases. So, as I was trying to find him help, I got more interested in this issue and I was starting to realize that for every other disease area, if you think about chronic diseases like Alzheimer’s, Parkinson’s, things like breast cancer, all of the advocacy groups, everybody says, let’s find a cure. These are difficult scientific problems. These are difficult medical problems, but we spend so many billions of dollars, huge amounts of pharmaceutical industry effort to try to find a cure. And that’s just not happening in this space.
And so I would see things like, oh, some researchers at a university are trying to make a vaccine for fentanyl. You say, well, if that’s possible, why isn’t this a huge national priority? Why aren’t we putting everything into this? And so that’s the kind of stuff that got me interested in, can we actually do a lot better? Why are there so few treatments? Why are the ambitions in this space so low? And I think it comes from a lot of things. It comes from stigma. People don’t believe that addiction kind of, as you say, like should theoretically be solvable. It should be possible to have, you know, a safe solution.
I think also when you have a multifactorial problem where you see that, you know, for Nick, who I’ve been working with, trauma is his core problem. It’s the childhood trauma. And then the addiction follows onto that really quickly. So you look at all the different causes, all the ways that poverty, trauma, social isolation, depression, anxiety lead to addiction. And then it seems like, well, if we have so many factors leading to addiction, we probably have to solve all of those factors to really solve addiction at a social level.
And so I think that’s a very appealing idea. But in fact, what we’re seeing in terms of weight loss and obesity with GLP-1 drugs like Ozempic is that you can have a really complicated problem. You can have something that’s caused by all sorts of social factors, psychological factors, companies pumping out synthetic foods that our bodies were just not adapted to, lifestyles that have totally changed from what we evolved to. You can have all these complicated things leading people to have higher cravings for food than they would naturally. But that doesn’t mean you have to solve all of that to really address the problem.
Chris Hayes: I’m glad you brought up GLP-1 drugs like Wegovy and Ozempic now because I was just going to say, when you first talked to me, I think the first conversation we had was prior to the big sort of Ozempic being introduced to market. And in the absence of that drug, I think it is harder —
Nicholas Reville: Yeah.
Chris Hayes: — to imagine that there could like, there’s a pill you take that makes you not, like not have this very complicated addiction or craving.
Nicholas Reville: Yeah.
Chris Hayes: And then to see this drug that has come along. And again, it’s relatively early, there’s been a fair amount of data that really does seem to basically do that. Like it reduces people’s cravings. The relationships they have to food for a million different reasons, and God knows my own is tortured sometimes. But it seems like there actually turns out to be like a biophysical mechanism and they kind of got in there and, you know, rewired it.
Nicholas Reville: I mean, a lot of people thought you could never have a safe weight loss drug. And these drugs seem to be remarkably safe. They reduce how much people die, which is kind of the ultimate measure. And as recently as five years ago, major pharmaceutical companies that were developing these drugs for diabetes, which is what they were originally designed for, were estimating zero sales in obesity because there had never been a successful obesity drug. You know, it’s very similar to the situation in addiction. Ten years ago we had multiple FDA approved drugs for obesity. A very small percentage of people took those drugs. They reduce your weight by a small amount. There was low efficacy, there was high side effects. They were just not appealing to people. And it was seen as a failed marketplace.
You don’t develop drugs for obesity. They’re expensive to study and they’re not going to work. It’s not really something you can solve with medicine. And now we’re seeing this area that you should avoid if you’re a firm or businessman, now is the most profitable area in the pharmaceutical industry. There’s a gold rush of other companies coming along with new drugs. And what’s really remarkable is that the GLP-1s, they were designed for diabetes. There was this side effect of reducing hunger and craving for food. And we’re also seeing that there’s a side effect of reducing craving for other substances and not just other substances, but even other behaviors. So there’s people saying they stopped drinking when they took this just as a side effect by accident. They weren’t even trying to stop drinking. They don’t crave drugs anymore. And there’s people who’s gambling addictions have been reduced dramatically when they’ve started taking Ozempic for diabetes or Wegovy for weight loss.
Chris Hayes: So you’ve got this situation where like we all know we have this enormous addiction issue. It’s specifically around opioids, partly because of particularly just how insanely dangerous and toxic fentanyl is and how it’s pushed out more and more of the opioid market and has led to this just shocking rise.
Nicholas Reville: The transition from heroin to fentanyl is really what drove the big spike in deaths over the past 10 years where essentially heroin doesn’t exist anymore in the U.S., and fentanyl has taken over completely. It’s much more dangerous, it’s more addictive, it’s harder to treat, it’s much easier to overdose because a sesame seed size amount of fentanyl can kill you, and so it’s very easy to accidentally take too much, and so it’s driven this just huge, huge spike in deaths.
Chris Hayes: So we’ve got this very obvious glaring social problem, along with all the knock-on effects.
Nicholas Reville: Yeah.
Chris Hayes: I mean, horrible trauma, social dislocation that come with the opioid crisis. The opioid crisis is not like an undercover issue. It’s front and center.
Nicholas Reville: Yeah,
Chris Hayes: It’s one of the sort of top three social crises in the country, probably. I mean, it’s usually, and yet, so the first layer of this is people conceiving of it being possible for there to be a medical intervention that would treat it. That we just, like, we have a few medical treatments for substance use disorder, they’re not great, people don’t like them, there’s a whole bunch of reasons they’re just not doing what we want them to do.
Nicholas Reville: Yeah.
Chris Hayes: So there’s a sort of ambition problem. Then there’s a kind of conceptual problem of like, could it even be the case that is this even a thing science could produce for us, right?
Nicholas Reville: Yeah.
Chris Hayes: A pill that could do this. If you get through those, then there’s the question of like, okay, well, why aren’t we doing it? And what would it mean? There’s a complicated interface between the federal government and public money and the way that pharma markets work —
Nicholas Reville: Yeah.
Chris Hayes: — that have to be engaged. And I’ve learned from you, from reading your stuff and talking to you, what is not working now and what would need to change?
Nicholas Reville: Yeah, I mean, again, the scope of this problem is huge and it goes way beyond opioids. Addiction, all together with tobacco, alcohol, opioids, meth, cocaine, causes 767,000 deaths in the U.S. every year. That’s more than cancer. And a lot of the cancer deaths are caused by addictions. So addiction is driving more deaths than really any other cause. And yet addiction drugs get less than 0.5% of the investment from pharmaceutical companies for drug development that cancer drugs get.
Chris Hayes: One two-hundredth of the amount on cancer.
Nicholas Reville: Less than one two-hundredth. Not only that, we spend more money developing drugs for lung cancer than we do for smoking, which causes 90% of lung cancer. So we’re investing in the wrong places and we’re not focused on how big this problem is. And I think that comes from that belief that this isn’t really curable stigma around. People should just take responsibility and do this themselves, just go cold turkey, which is just not an effective intervention for the vast majority of people.
And it comes from a bunch of historical reasons that criticism that drug companies received in the past when they started to create drugs for addiction that led them to feel like it’s a kind of a no-win situation. People are going to say they’re profiting off of addiction. Low sales has led the industry in a very narrow way, in the same way that it did in obesity, has led them to think that you cannot have successful drugs in this space when actually it’s the low efficacy is the issue.
And if you invest in good drugs, sales will really grow quickly. So what we’ve been writing about and what we believe is that we can solve this market failure by creating some incentives to get the pharmaceutical industry active in this space again.
Chris Hayes: More of our conversation after this quick break.
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Chris Hayes: So, I mean, there’s some part of me that’s like, there’s some deep alarm bell that goes off in me where you’re like, we’re going to get big pharma to solve addiction.
Nicholas Reville: Yeah.
Chris Hayes: And I’m like, oh, I don’t know.
Nicholas Reville: Yeah. I mean, it took me a while emotionally, I think, to get to this place. You know, we all saw what the Sackler’s did, Purdue Pharma, in terms of pushing pain pills, Oxycontin. You know, they were a huge driver of the recent opioid crisis, no doubt. So you should be skeptical. But it is possible to create safe treatments. The existing treatments that we have for opioid use disorder are opioid-based. And we need to move to a place where we have non-opioid-based treatments that have no addictive potential. And the same is true for painkillers. It’s kind of agonizing for me that the opioid settlement money was not used to develop non-opioid painkillers, because that’s really what we need.
You can’t just tell people, oh, your pain isn’t real, you don’t really need —
Chris Hayes: Right.
Nicholas Reville: — so much pain pills. We need to find options that actually work for people.
Chris Hayes: Will you talk to me a little bit about the development of AIDS research and drugs, because I know this is something that you’ve spent some time thinking about, and was an interesting place where different parts of the system, federal research money, National Institutes of Health, pharma kind of worked in different ways to take what, again, it really is an amazing thing. Thirty years ago, we kind of were talking about AIDS the way that we talk about the opioid crisis now.
Nicholas Reville: Yeah.
Chris Hayes: Just a mass horrifying crisis and disaster laying waste to lives and families and just churning through people. And yes, there were some interventions you could do around like public health and safe sex education, things like that, but —
Nicholas Reville: Yeah.
Chris Hayes: — that wasn’t getting the job done. And now it’s like basically cured, which seemed impossible 30 years ago. Truly, I did not think that would be the case.
Nicholas Reville: I mean, HIV is one of the most challenging scientific problems that biology has ever faced. It’s a virus that works in a completely different way. We had no strategies for it. We didn’t even know what was causing AIDS for a long time. And there was a real sort of Manhattan Project mentality of let’s bring together the best resources, public-private resources, and make a run at this. And at its peak, AIDS was killing half as many people as died last year from opioid overdoses. And, you know, a tiny fraction of the number of people that die every year from tobacco or from alcohol.
So we pulled together, you know, when we felt like there was an urgent crisis and we needed a medical solution. And that’s never happened in the space of addiction. But the number of lives you could save, the amount of life extension that we could provide to people, the amount of lost productivity is just tremendous.
Chris Hayes: How much did it matter that we started that Manhattan Project idea? How much did it matter that we started putting money towards AIDS research, that there was basically just a lot of resources directed towards it?
Nicholas Reville: It mattered tremendously. I mean, there’s government funding every year for alcohol research, drug addiction research in the NIH. And there’s a lot of really important basic research, but academic research does not make medicine. In the system that we have now, medicine is created by pharmaceutical companies. So if you want to have good medicine, you need to have a private sector, public sector collaboration to translate those results into medicine. And you want to have people that are profit motivated to say, let’s get this to market first. Let’s sell tons of this stuff to everybody because there’s an urgent medical need. HIV is spreading quickly. We need to get there first and try to solve it before our competitor does. And when you do that, so when you have the best minds and energy focused on the public sector, the private sector, you can move very quickly.
Chris Hayes: Yeah. The other sort of most recent example is the Operation Warp Speed. And to me, the one genuine policy achievement of the Trump administration, like true actual good thing they did that for all my criticisms of him, and I don’t think he really had anything to do with it, I think probably just like the name, it was amazing. And again, what is your understanding of how much policy played a role there?
Nicholas Reville: Well, policy was huge. I mean, Operation Warp Speed was a policy project. It was about offering things like advanced market commitments to the drug companies to say, if you make this, we’re going to buy a lot of it. And we’re going to help you get your factories going quickly. And we’re going to help get this off the ground. And we’re going to really pave the way for this to get tested and approved as quickly as possible. And we’re in a similar situation now in terms of GLP-1 drugs where we have really good evidence. We have evidence from phase two trials. We have tremendous retrospective studies that show that people that receive a GLP-1 drug like Ozempic for something like diabetes or for weight loss, go on to have a 50% lower chance of developing an alcohol use disorder or having an opioid overdose.
Chris Hayes: Really?
Nicholas Reville: So people that are receiving these drugs are in a sense being, for diabetes, are in a sense being vaccinated against future substance use disorders.
Chris Hayes: Oh, is that true?
Nicholas Reville: Yes, this is true. There’s a whole bunch of studies. Our organization now, we’re funding a study at the VA that’s going to be looking at veterans, overdose rates in veterans who have a history of opioid use disorder and who have received Ozempic for diabetes. And we’re going to be looking at what is their rate of overdose. And if it matches the population rate, it’s going to be something like a 40 or 50% reduction. This is just an unintended side effect. This is not like somebody saying, I’m going to try to quit opioids. It’s just, I got this drug and then later on, just something bad didn’t happen, that I wasn’t even trying. And you can see this, if you know anybody, something like 10% of adults are now taking one of these drugs, brilliant in its class.
Chris Hayes: Really, 10%?
Nicholas Reville: Yeah.
Chris Hayes: That went fast.
Nicholas Reville: It’s growing really fast. So almost everybody listening to this knows somebody, whether you know it or not —
Chris Hayes: Right.
Nicholas Reville: — you know somebody who’s taking this. And if you ask them, has this made you want to drink less alcohol? Almost everybody you ask will say yes, whether they were trying to or not. We’ve heard reports of people saying, I’m kind of bummed because I love going out on Friday night with my friends and having like six or seven drinks. Now I can’t have more than one or two. That’s all I can have. And I wasn’t trying to reduce my drinking. But it just, what we’re seeing is that this class of medication is reducing craving, not just for food, but for everything. And that there’s some kind of a craving mechanism in the brain that can just be reduced.
And I think that in many ways craving is a better framework for thinking about addiction. It’s more specific. It’s something that all of us have in different amounts for different things in different ways. And you can start, if you start to think about craving and you have medicines that you can use to kind of intervene earlier for people. So, let’s say you’re worried that your kid is starting to use opioids, they’re partying, you can tell that they’re going down a dark path, you’re worried. You’re not just going to suddenly put them on methadone because now this is just like a full life commitment. Like you’re going to do that only when you’ve —
Chris Hayes: Right.
Nicholas Reville: — tried a lot of other things. But with a GLP-1, you could say, okay, my spouse is starting to drink a little too much. And you say, honey, like are your cravings, you feel like you’re having cravings for alcohol? You don’t have to wait until this person hits rock bottom, force them to sort of identify as an alcoholic, as an addict for the rest of their life, take on this whole identity. You can intervene and say, let’s just bring your cravings down a little. I’m not saying you have a big problem, let’s just take your cravings down. And that opens up a whole other world of intervention and treatment. Not to mention that these drugs are given once a week. So you can say, look, every Sunday, I’m going to give you your shot and that’s just something we’ll do. And we’ll just kind of keep things chill. And it just, it creates a completely new landscape for how we treat addiction.
Chris Hayes: That point about modulation as opposed to either or is so key because everything in the way we talk about our relationship to substance use disorder is like even the I’m an alcoholic, that’s an identity. I am an alcoholic. I’m a specific kind of person. That specific kind of person has a specific relationship to this specific drug, which means that I cannot drink. And I’m not saying this with like any shade. I’m saying like this is the model that has been —
Nicholas Reville: Yeah.
Chris Hayes: — wildly effective for millions of people, people I know, people who —
Nicholas Reville: Yeah.
Chris Hayes: — say their entire life and flourishing is due to this model, right? But it is a kind of binary model. It’s like you’re an addict or you’re not. That’s a thing you are or you’re not. You can —
Nicholas Reville: Abstain.
Chris Hayes: — I’m a heroin addict or I’m not. And the idea of like something in between and an intervention that isn’t so comprehensive to your life doesn’t label you as a thing —
Nicholas Reville: Yeah.
Chris Hayes: — that can still be effective, is a mind blowing thing to contemplate.
Nicholas Reville: Yeah, I mean, we have mutual friends who’ve had AA —
Chris Hayes: Yeah.
Nicholas Reville: — you know, Alcoholics Anonymous has been transformative for them.
Chris Hayes: Yeah.
Nicholas Reville: And the abstinence model is great for a lot of people. For many people, it’s a good goal to shoot for, but it’s not necessarily the best way to reach a lot of people with treatment. Only 3% of people with substance use disorders take medication. You know, for diabetes, it’s 80%. We’re not even remotely in the ballpark of treating all the people who would qualify for this. And if you can provide easier options, less side effects, positive health benefits, it’s easy to convince someone to take a drug where they might lose five pounds, lose 10 pounds.
And these drugs reduce inflammation in the brain, they are reducing depression. Novo Nordisk is studying Ozempic in a large phase three trial, which they would only do if they had a lot of confidence in a phase three trial for Alzheimer’s disease because it seems protective to the brain. So there’s all kinds of additional benefits from taking this and you can just change the entire framework of the conversation away from abstinence and addiction into something that’s just like, look, we all face this in different ways. Sometimes a craving gets too high. Let’s bring it back into moderation.
Chris Hayes: So it sounds to me like what you’re saying, I mean, it sounds like you think that GLP-1s might just actually be the thing.
Nicholas Reville: I think GLP-1s are the first step. This is like a lucky sort of gift that we’ve received. This came out of metabolism research. It’s sort of an amazing coincidence that it also reduces cravings and has all these other benefits.
Chris Hayes: Peptides and lizard saliva, I think was the original —
Nicholas Reville: Yeah, from the Gila monster.
Chris Hayes: Yeah.
Nicholas Reville: You know, GLP-1s are a version of a hormone that we all have that modulates these things. And this is a version that lasts longer and you can boost your level and it reduces your cravings. This is a chance to just expand people’s willingness, reduce stigma. And I think once we can start to get a few effective popular. A popular is so important. If you run a methadone study, it works really well while people take it. But a year later, the vast majority of people stopped taking it. And it’s very difficult to convince people to start taking it.
Chris Hayes: Is that hassle and stigma mostly?
Nicholas Reville: Yeah, the hassle, the stigma.
Chris Hayes: Yeah.
Nicholas Reville: You know, instability in their lives and side effects. Being on opioids, even methadone, long term, it messes with your sleep.
Chris Hayes: Yeah.
Nicholas Reville: You know, it affects your health in all kinds of ways. It’s not where you ideally want to be. I mean, people should do it. It’s great. We can do better. We need drugs that people are eager to take, that they want to take to help them. And I think if we can bring GLP-1s to market and Eli Lilly is now saying that they are going to begin some trials, so that’s really good. If we can start to bring GLP-1s to market, then I think we will have follow-ons. We will show that this is a successful type of drug and we can start moving up that ladder towards treatments that are really designed initially for addiction, not initially for diabetes, and kind of build better and better and better medicines.
Chris Hayes: When you say Eli Lilly bringing to market, you mean specifically for addiction.
Nicholas Reville: Yeah. So, Eli Lilly is going to be testing some GLP-1 drugs. They already make Mounjaro and Zepbound, which are the same molecule. They’re going to be testing some new molecules specifically for substance use disorders. They just announced that a couple of weeks ago. And CASPR, my organization, we’re also trying to do this. So we’re trying to bring large scale trials of a GLP-1 through FDA approval and try to bring something to market as a nonprofit that can get to people quickly.
Chris Hayes: What are the obstacles to testing, like this has not been an active market, drugs for substance use disorder despite the fact that there’s millions of people who could stand to benefit. Why is that the case?
Nicholas Reville: Well, I think pharma has been skeptical because as I’ve said, they’ve seen low sales. There are specific things that we’re proposing like the way endpoints are defined. So a lot of endpoints for substance use disorder trials, sort of the outcomes that they’re looking at are basically based in abstinence. So the FDA has set standards that are sometimes you might reduce somebody’s heavy drinking days completely so they are no longer having any heavy drinking days, but they still have a drink or two a week. And that would qualify them as non-abstinent. And so pharma companies have seen that and they’ve been reluctant.
Chris Hayes: Wow, that’s interesting.
Nicholas Reville: They might say, we have a drug that works really well, but we don’t know if it’s going to get through FDA approval. So we’ve been talking to the FDA, we’ve been talking to lawmakers about trying to improve those endpoints and modernize them so that it sends a message to the industry that yes, we actually want you to be making medicines for this. Like we’re eager to have you make medicines for this. We also want to expand the priority review voucher program.
Chris Hayes: What’s that?
Nicholas Reville: So this has been a really successful FDA program for rare diseases. So there’s diseases where there’s only a thousand patients in the country. And so it’s totally uneconomical for a pharmaceutical company to make a drug for a thousand people. But we want those people to have a chance and we want to encourage small biotech companies to go after this. So, the priority review voucher, it’s a no cost way where we give a voucher to a company that develops one of these drugs for rare disease. And that voucher can be resold to a larger pharmaceutical company to accelerate the approval of one of their drugs for whatever drug.
And these vouchers are resold for $100 million or more. So, speeding up approval of a drug is tremendously valuable to pharmaceutical companies. And so this is a way that the FDA lets you essentially cut the line, you get a voucher to cut the line if you’re developing a drug for a disease area that’s been neglected. And so what we’re saying is addiction has been neglected. We’ve had 222 approvals of cancer drugs in the past 25 years, since the year 2000. And we’ve only had six approvals of addiction drugs. And of those six, three of them are just reformulations of the same molecule.
So we need dramatically more drugs coming into the pipeline from small biotechs, you know, being bought by big pharmas and brought to market, large scale trials. And we should be doing everything we can to help facilitate the process of running those trials.
Chris Hayes: We’ll be right back after we take this quick break.
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Chris Hayes: Are there people doing this kind of research? Like, is there stuff happening at the research end that’s not getting to market? Like, is there a mismatch? Are there actual scientists out there who are like, we think we’re onto something having to do with —
Nicholas Reville: Oh, yeah.
Chris Hayes: — addiction?
Nicholas Reville: I mean, that’s how we know about this, is that there’ve been researchers who have done animal studies showing that, you know, rats stop liking heroin when they take this, stop drinking alcohol. The human retrospective studies that I’ve talked about, we have data scientists looking through health records and saying, oh, it looks like when people started taking Ozempic, they stopped developing an alcohol use disorder. And then there’s been small phase two trials from academics. So they’ve been just starting to give people drugs like Ozempic, Mounjaro, and showing that their cravings and their consumption dropped dramatically.
So there’s a whole bunch of smaller phase two academic trials that are happening. And those are funded by the National Institute of Alcohol and the National Institute of Drug Abuse. And those are great. Those are the groundwork that we need. But those organizations that, you know, whether it’s the academic research center or the government agency, they’re not set up to bring a drug to market. And pharmaceutical companies have been afraid to take a successful GLP-1 that’s already in the market and run a study on addiction for it because they’re worried that they will develop, you know, you could run a trial on somebody, someone could die in the trial from some other reason.
Chris Hayes: Yeah.
Nicholas Reville: And then you might get people saying, oh, Ozempic causes suicide.
Chris Hayes: I see. Right, because it’s a population with a high baseline of mortality and morbidity.
Nicholas Reville: Yeah, it’s an unstable population. They’re hard to study often because there’s instability. There’s a high rate of dropouts in addiction trials. And so in pharmaceutical companies, because they haven’t been working in the field of addiction, they don’t have experience working in the field of addiction. So it feels to them like it’s all risk, no reward, and they’re just going to focus on that’s already working.
Chris Hayes: There’s also, to me, and again, it seems like there’s a PR problem because it’s like a little bit of like, from the people who brought you the opioid crisis comes —
Nicholas Reville: Oh, yeah.
Chris Hayes: — the solution to the opioid crisis.
Nicholas Reville: Yeah.
Chris Hayes: Like, just the idea of like getting people to remember how this whole thing happened, we’re here to solve it. Like there’s a way to market your way out of that. I mean, honestly, there is because like what matters is solving the problem. But I do wonder how much that is looms over all of it.
Nicholas Reville: I think, you know, pharma is very aware of their reputation. And I think they don’t want to get dragged into a bunch of, you know, criticism.
Chris Hayes: Yeah.
Nicholas Reville: And I think that’s something that advocates need to be ready to say, okay, we do need pharma’s help here. And I think the government needs to send signals that we want you, we’re going to help facilitate, we want to make this easy for you. Because until we have a new way of developing drugs and bringing them to market, pharma is how they get there. And we have a huge medical opportunity here that’s just sitting on the shelf. And people are already getting this off label from some doctors, but then they have to pay out of pocket for it —
Chris Hayes: Right.
Nicholas Reville: — being prescribed this for substance use disorders.
Chris Hayes: Really, is that happening?
Nicholas Reville: Yeah, people are going to compounding services and they’re lying about their weight to say that they need it for obesity and then they’re using it to quit opioids or stop drinking. So there’s communities on Reddit that are doing this. There’s lots of doctors across the country that are starting. We’ve been publishing stories from doctors who are prescribing this to patients on and off label for substance use disorders. And they’re just seeing remarkable results.
Chris Hayes: Who have you been talking to about this? I mean, you’ve got a whole bunch of people involved in this now and you got a nonprofit. What are those conversations like and how receptive have people been to this?
Nicholas Reville: I think there’s a window here where there’s maybe more receptivity than there might’ve been in the past. I think what’s happened is that you’ve seen on both the left and the right, I think politicians are starting to privately admit. And what we’ve been hearing is that people no longer really believe in the solutions that their side has been pushing in the past. So —
Chris Hayes: What do you mean by that?
Nicholas Reville: We’ve been trying the drug war for over 50 years, right? And the drug war is obviously not working. And so, you still have people on the right that want to focus on border security, things like that. But fentanyl is so easy to smuggle. It’s 1/50th the size of heroin at the same strength. You can put 8,000 doses in a golf ball. So you’re not going to stop smuggling. It’s just not realistic.
And then I think we’ve seen on the left, decriminalization in Oregon, followed by recriminalization, all kinds of debates in San Francisco about are we being too lenient or too strict and honestly, most of those policies did not make a difference in either direction on overdose rates. And so I think there’s some level of fatigue for the kind of political battles around this.
Chris Hayes: Yeah.
Nicholas Reville: And really we’ve been arguing about 5% of the problem. We’ve been arguing about, you know, should we expand or restrict methadone access? You know, what should we do about decriminalization or recriminalization? How much border security should we have? These are things that just are making little, tiny incremental differences. I’m not saying they don’t do anything. I have opinions about all of them, but they’re not the big problem. The big problem is that we have a medical issue that tens of millions of Americans face that kills 750,000 Americans a year.
And we’re not working on making new medicines for it. We’re not trying to actually solve the problem. We’re at the beginning of the problem, which is the demand, which is the craving that people live with and which is not something that you can just control. Like we’ve been thrown into this environment with artificial foods, artificial substances that we never evolved for, they trigger our brain. And for some people that just spikes your cravings. And it combines with your personal history, your trauma, your life situation, and it just becomes something that is not within your control. And I think some of the conversations around, you know, Ozempic, food noise, the way that we’re starting to understand kind of how food craving works for people and how much mental energy people are expending just on not eating all day —
Chris Hayes: Yeah.
Nicholas Reville: — and how great it is just psychologically to relieve that burden, not even in terms of metabolic health. I think that there is openness now to trying something different, and I think that this is a consensus path. So we have a series of policy proposals that we published with the Federation of American Scientists and with the Institute for Progress, and we’re calling for increased funding, expanding the priority review voucher program, updating the endpoints, providing other incentives and collaborative mechanisms to work with pharmaceutical companies to develop drugs. And I think this is a consensus political position. I think it’s not a left position, it’s not a right position, it’s about innovation and it’s a very American solution to a very American problem.
Chris Hayes: Yeah, it’s interesting to me because what you’re saying here when you first told it to me is like, I was trying to place it ideologically.
Nicholas Reville: Yeah.
Chris Hayes: I think there’s different ways and I think you’ll probably get criticism from all sorts of different directions. But I think that it doesn’t actually have to be ideologically coded.
Nicholas Reville: Yeah.
Chris Hayes: Like diabetes drugs aren’t.
Nicholas Reville: Yeah, and that’s the point.
Chris Hayes: I was about to say the vaccines weren’t, but nope.
Nicholas Reville: I mean, the GLP-1s are so popular now across the spectrum that —
Chris Hayes: Yeah.
Nicholas Reville: — a lot of people have personal experience. And I think that anyone who’s tried it is going to say, it actually makes sense to me that this could work for addiction. And anyone who has a family member that’s struggling with this is going to say, God, I wish we had a medicine. I wish there was something I could drive over to their house, my cousin’s house, once a week, give them a shot and at least reduce their risk to some degree. And so I think that fundamentally, when people think about this, they want better medicine. I don’t think it’s going to turn into a political thing. And I think it affects every district in the country. It feels like we can really make progress across the political spectrum.
Chris Hayes: Have you talked to politicians and have you had receptive conversations from politicians?
Nicholas Reville: Yeah, we’ve been starting to talk to congressional offices since we released the report a couple of weeks ago. There’s a lot of receptivity. I think it really also fits with what you’re seeing, the interest in government efficiency in making systems work better, better collaborations in industry, even our new co-president, Elon Musk, tweeted out the other day that nothing would be better for public health in the country than making GLP-1s extremely cheap and available to people. And I think that it’s something that is going to —
Chris Hayes: Now, I really think it’s a bad idea.
Nicholas Reville: We all have to leave our biases aside about who the messenger is, who we need to collaborate with to get this done, because we have an amazing opportunity. And addiction, you know, 60% of crime is related to drugs or alcohol. So much intergenerational trauma.
Chris Hayes: Yeah, I mean —
Nicholas Reville: Just like division among neighbors, like fear in a neighborhood, if there’s one break in, everybody’s afraid for 10 years. Division in families. If your family member gets cancer, everybody pulls together like it’s horrible, but you kind of know what to do. It’s unifying in a way. If a family member is addicted, it’s caustic and it drives the family apart. It becomes so difficult. It’s either so much anger in all directions and it’s just really, really divisive. And so if we can find a medical solution and it’s clear scientifically that we can, we should be putting everything we can into doing it.
Chris Hayes: You know, one thing I also think that is interesting about this that I’ve been thinking about a lot for a project I’m into this year, is just like, I think the developments in the last decade, particularly, have led people to just be incredibly skeptical of progress or of solving problems, that like things can only be bad. And to be particularly kind of looking for what the con is —
Nicholas Reville: Yup.
Chris Hayes: — when someone like you, music man style comes in to be like, a magic pill for addiction. Well, what are you up to? And I do think it’s useful to remember, like to go back to the story of AIDS.
Nicholas Reville: Yeah.
Chris Hayes: There are other examples of what happened with CFCs in the atmosphere of the Montreal Treaty, like big problems that seemed really hard and not solvable. And then we solved.
Nicholas Reville: This is the history of medical science. I mean, think about antibiotics. Can you believe that we invented antibiotics, that you can just cure these diseases that have been around for centuries and they just —
Chris Hayes: Right.
Nicholas Reville: — go away, they’re not a problem anymore. All the vaccines that have just eliminated diseases in our lives. If you’re feeling like, oh, it’s unrealistic that we could solve this medically, think about all the unrealistic things that we’ve done, and including what these drugs are doing for weight loss and obesity. Obesity dropped for the first time ever in the United States last year, and it’s because of these medicines.
Chris Hayes: Is that right?
Nicholas Reville: Yeah. And they’re making people live longer. So a realistic view of medical science is that miracles happen. We get a miracle every, you know, 5, 10, 20 years in medical science and it’s just, they happen all the time. So you’re being unrealistic if you’re too skeptical.
Chris Hayes: Have you been having conversations on the pharma side and what have those conversations been like?
Nicholas Reville: Yeah. I mean, you know, we’ve talked to pharma executives at a whole bunch of companies. I mean, generally, there’s just a lot of risk aversion there. They’re worried about what could happen in trials. They don’t have programs in this already. And it’s just not their field. And so that’s just a sign that something’s going wrong in the marketplace. And we need to entice, coax, convince, and send signals that we really want activity happening here. The development at Eli Lilly is really promising. We talked to senior leadership there. They seem very committed to doing something with GLP-1s. It’s going to be with a new molecule. It’s going to take a while, but I think that’ll be huge.
And there’s a really big opportunity globally because semaglutide, which is Ozempic, is going to be generic outside of the U.S. in 2026 around the world.
Chris Hayes: That’s the Danish company. That’s the Danish one.
Nicholas Reville: Yep. So Ozempic is going to become generic and very cheap globally next year.
Chris Hayes: Whoa. Dude, that is wild, worldwide generic Ozempic in 2026.
Nicholas Reville: Yep. So it’s going to be everywhere. And alcohol in particular is a global problem —
Chris Hayes: Yeah.
Nicholas Reville: — in every country. And so is smoking in almost every country. So, the global health potential of having phase three quality evidence, testing these drugs, the kinds of trials that will lead to doctors prescribing around the world and medical agencies recommending this globally, I think this is the highest ROI opportunity in public health by far, is getting a phase three trial of semaglutide.
Chris Hayes: For addiction specifically.
Nicholas Reville: For alcohol use disorder, opioid use disorder, smoking, and for stimulants. There are zero FDA approved drugs for cocaine or methamphetamine.
Chris Hayes: Wow.
Nicholas Reville: But we think GLP-1s may be effective, not as effective as they are for alcohol.
Chris Hayes: Interesting.
Nicholas Reville: But significantly effective.
Chris Hayes: And so phase three is the one that’s like just pre-commercial.
Nicholas Reville: Yeah. Phase three trials are the ones that provide the largest number of patients, highest quality evidence designed for the FDA to make sure that they feel confident that once they get the results, if the efficacy is good enough, then the drug will be approved. And what’s wonderful about the GLP-1 drugs is that they’re remarkably safe. The safety profile for the entire class is way better than most drugs. So there’s really good chance that you know, if Lilly brings a new set to market, that they will get through the trials. Safety is often one of the biggest reasons why these drugs fail.
Chris Hayes: Yeah, I mean, understandably, right.
Nicholas Reville: Yeah.
Chris Hayes: So they’ve announced that they’re going to do a new molecule for phase two. No one is at phase three yet globally.
Nicholas Reville: Correct.
Chris Hayes: And are other countries, are there other groups like CASPR in other countries? Is this something that people are thinking about in other countries?
Nicholas Reville: Not that we know of.
Chris Hayes: That’s interesting.
Nicholas Reville: But please get in touch if you’re listening.
Chris Hayes: Yeah, if you’re listening to this and you want to reach out. If people want to learn more about what CASPR is up to, like where should they learn that?
Nicholas Reville: We have a Substack. It’s a blog called “Recursive Adaptation.” So you can search for that and you can also check out our website. It’s caspr.org, C-A-S-P-R dot O-R-G.
Chris Hayes: I’m curious just how this has affected you about how you think about addiction. Like, has it changed the way you think about the, to go back to the sort of philosophical roots of it, how you think about what it is?
Nicholas Reville: Yeah, it’s definitely changed it. I mean, I think for me, I think that the evidence that’s come out around cravings really creates this level of granularity as you think about it, this specificity where you say, okay, there can be all kinds of things that lead to a craving. So there could be depression, anxiety, some life disruption, trauma, all kinds of stuff that triggers a craving once you have some kind of a dependence on a drug. It can just be the use of the drug that leads to the craving.
Some people, I think it’s biological. They have their first sip of alcohol and they’re like, this is it, this is my thing. Alcohol is my thing and they just can’t stop. So there’s all kinds of things that can lead to cravings, but cravings I think are really a more specific and more helpful way to look at what’s happening in addiction. And if you reduce those cravings, you can give people a chance —
Chris Hayes: To break it.
Nicholas Reville: — some space in their lives —
Chris Hayes: Yeah.
Nicholas Reville: — to address the other patterns, the other circumstances that have led them in that direction.
Chris Hayes: To me, what’s so striking about this language is a craving sounds so normal and relatable and addiction sounds pathological.
Nicholas Reville: Exactly.
Chris Hayes: And that is such a huge difference.
Nicholas Reville: Exactly. And I think we need to start thinking of this as a spectrum, a spectrum of what are your cravings for what and when do they enter a dangerous level or just an uncomfortable level. I think it’s possible that you could have people who’ve been white knuckling sobriety for years. And we’ve heard stories like this. Someone white-knuckling sobriety for years, they start taking Ozempic for diabetes, and they’re like, oh, this is such a relief.
Chris Hayes: Right.
Nicholas Reville: Like, I don’t have to try so hard every day —
Chris Hayes: Right.
Nicholas Reville: — to not do something, even though I haven’t done it, even though I haven’t done it for years. One of the amazing studies that was done by Penn State, inpatient study for people with opioid use disorder, showed that with a GLP-1, stress levels were being decoupled from craving. So, you would have people whose stress was rising, and that’s always been seen as a directly correlated to cravings rising.
Chris Hayes: Yeah, I feel it in myself.
Nicholas Reville: And people were seeing cravings stayed flat, even in patients as their stress level rose. Not with placebo, but yes, with the GLP-1. And so we start to distinguish, when we start to get more specific, I think we start to reduce the stigma, it becomes more relatable, and we get smarter about how to solve it and how to communicate about it.
Chris Hayes: Yeah, and the fact that starting with food, which is a unique substance —
Nicholas Reville: Yeah.
Chris Hayes: — among all their substances because, you know, one of the things that’s very hard with food and for people that have complicated or disordered relationships with food is that abstinence isn’t an issue. It is not an option, right? So it’s the one place where abstinence isn’t an option, people make conclusions about your relationship to food based on how you appear in the world. You could have a really bad gambling addiction and when you walk in public space, no one knows that.
Nicholas Reville: Yeah.
Chris Hayes: So there’s always been something distinct about food as a source of addiction or compulsion or craving because that’s the one place where you just can’t take the abstinence route.
Nicholas Reville: Yeah.
Chris Hayes: So you got to deal with it. And that is what makes it so hard in some ways. It’s very hard to do an AA for food.
Nicholas Reville: It’s really hard. And I think it’s going to be very interesting to see what RFK does as he comes into this administration.
Chris Hayes: I don’t know if he has 50 votes yet, but we’ll see.
Nicholas Reville: We’ll see if he gets approved. But there’s this new interest, I think, on both the left and the right in looking at addictive foods. And what the science is telling us is that food cravings and food addiction are basically indistinguishable in your brain from cravings and addictions to other things.
Chris Hayes: Yeah.
Nicholas Reville: And we should be giving people help because they’re being put in a food environment that is very hard to control for anybody.
Chris Hayes: Nicholas Reville is the co-founder and executive director of CASPR, the Center for Addiction Science Policy and Research. That was great, man. You’ve given me a burst of hope.
Nicholas Reville: Oh, good. Thank you so much.
Chris Hayes: Once again, great thanks to my buddy Nicholas Reville, co-founder, executive director of CASPR. You should check out what they have to say more in depth at their Substack. We should also note that as a 501(c)(3) nonprofit, Nicholas’ group does not receive any money from pharma companies. Obviously that’s important.
You can e-mail us at withpod@gmail.com. We’d love to hear your reaction to that episode. I am totally fascinated by the topic and kind of thinking about it a lot, so I’d love to hear what you think. You can get in touch with us using the hashtag #WITHpod across various social networks. You can follow us on TikTok by searching for WITHpod. You can follow me on Threads, the site formerly known as Twitter and BlueSky. I am @chrislhayes across all three of them.
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