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My guest today, Rick Doblin, has spent the last 37 years trying to get F.D.A. approval for a breakthrough treatment for post-traumatic stress disorder, PTSD. Against all odds, it looks like he’s actually going to succeed.
DOBLIN: If we would have waited for pharmaceutical companies to develop MDMA-assisted psychotherapy, we would still be waiting today.
Welcome to People I (Mostly) Admire, with Steve Levitt.
Few people dream as big as Rick Doblin. And among those who do, almost no one has the brilliance and the perseverance and the luck to turn those dreams into reality. I’m so looking forward, as I talk to Rick today, to try to figure out what it is about him that allowed him to defy the odds.
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LEVITT: So I’d love to start with you educating me a little bit about post traumatic stress disorder, PTSD. How does PTSD affect the brain? What are the current estimates of the prevalence of PTSD in society? And what kind of success rates have we seen with traditional therapies that address PTSD?
DOBLIN: Well, the Veterans Administration recently estimated that there’s 13 million PTSD patients in America. And those are just the people that qualify for a diagnosis of PTSD. There’s a lot of people that are suffering from trauma that impacts their behaviors that doesn’t rise to the level of a diagnosis of PTSD. What we know from some neuroscience studies is that if you have PTSD, there’s a hyperactive amygdala where fear is processed, and there’s a reduction of activity in the prefrontal cortex where we think logically. So there could be a sound that might remind somebody of an explosion or somebody wearing clothes that might remind them of an attack or something like that, and with the prefrontal cortex activity reduced, they don’t really have the time to sort it out. Is this really a threat or not? They immediately go to the threat, particularly with the hyperactive amygdala. Then there’s a reduction of activity and connectivity between amygdala and hippocampus, where memories are put into long-term storage. So you’ve got this traumatic memory that is constantly in short-term memory as if it’s about to happen again or it’s still happening. It’s never fully processed. As far as what the therapies are that we have currently available, the S.S.R.I.s, which are Selective Serotonin Reuptake Inhibitors, are the main and the only drugs approved by F.D.A. for PTSD — Zoloft and Paxil. They help in about a third or so of the people, sometimes more. But what they basically do is reduce symptoms. They don’t get to the core of the trauma. And they require daily dosing, often for months or years and years, and they often have significant side effects. Psychotherapies are also effective in some ways for treating PTSD, particularly prolonged exposure and cognitive-processing therapy. The V.A. just did a study — it took them about six years. It was 900 veterans, and it was comparing prolonged exposure with cognitive-processing therapy. And what they showed is that those therapies are so difficult for people because you are asking people to recall the trauma, recall the worst things that they’ve ever happened to them, and then repeat over and over about it ‘till they get desensitized. So that around half the people in the study dropped out. So I think we have over a million veterans on disability for PTSD, costs the V.A. about 17 billion dollars a year just in disability payments. And there’s a general perceived need in the entire field of psychologists and psychiatrists and psychotherapists for new treatments.
LEVITT: So you really focused on veterans, but I think there’s this growing understanding that PTSD is much broader. I saw a fascinating study that suggested that a lot of kids who grow up in an inner-city environment, they have very high rates of PTSD. And it’s been argued that the PTSD affects how they respond to conflict, and that is one of the major contributors to the high rates of gun violence among young men in the inner city today. Which, really, when I first heard it, I was thinking, wait, did that make any sense? But the more I’ve thought about it, the more it’s really beginning to hit home as a problem that’s just fundamental.
DOBLIN: It does make sense. And while the media mostly does focus on the veterans, roughly two-thirds of the people in our research studies are women. Most of the people that have PTSD in America have it from sexual assault or trauma or domestic violence. A relatively small proportion are actually veterans; but the veterans are the ones that have the most appreciation from the society. And that’s where we’ve had the most attention. But it is important to say, in our Phase 2 studies, what we learned is that our treatment works regardless of the cause of PTSD. And the S.S.R.I.s that were approved for PTSD — they worked better for some reason in women than in men, and they didn’t work in combat-related PTSD.
LEVITT: Okay, so your organization, MAPS, M-A-P-S, has spent decades doing clinical research on an alternative approach to treating PTSD that combines therapy and pharmaceuticals. But before we go into the specifics of that treatment, could you describe the results you’ve obtained in the Phase-3 trials, the final trials you’ve carried out in the long process of trying to obtain F.D.A. approval? What sort of success rates have you seen in treating PTSD in these studies compared to traditional approaches?
DOBLIN: Okay, the results that we’ve gotten have basically taken us 37-and-a-half years. So I started MAPS in 1986. It wasn’t until 1992 that we got the first permission for the Phase 1 study. Then it was around 2000 that we got the first permission for the Phase 2 study in PTSD patients. That took us 16 years ‘till 2016. And then starting in 2018, we began our Phase 3 studies. And we published in Nature Medicine in 2021. The results were pretty amazing. Two-thirds of the people in our study at the two-month follow up after the last experimental session no longer qualified for a diagnosis of PTSD. Now these were people that had PTSD an average of 14 years or more. And we enroll people who have previously attempted suicide or suicidal behavior — around one-third had done that. So we had two thirds no longer qualified for a diagnosis of PTSD, and another 21 percent had clinically significant reductions of PTSD, even though they still had PTSD. And so over time or with more treatments, they might fall below that threshold. So we had an 88-percent response rate, which was remarkable compared to the currently existing therapies and pharmacotherapies.
LEVITT: So if someone accepts these study results, it’s almost like a miraculous advance. My understanding is that most new drug applications at the F.D.A. these days are actually quite incremental. That this sort of breakthrough is definitely the exception, not the norm. Is that your understanding as well?
DOBLIN: Very much. And actually F.D.A. did grant us breakthrough therapy.
LEVITT: That’s like a formal thing the F.D.A. does?
DOBLIN: Yeah. There’s a category called “breakthrough therapies.” What it means is that you have extra meetings with the F.D.A. They’re committed to trying to facilitate the research that you’re doing. And also there’s shorter review times. So that if you do get breakthrough therapy as a pharma company trying to develop a drug, that’s a real boost in expediting the process.
LEVITT: It’s sad that you’re talking about an expedited process, when just in the last breath you told me you’d been — 37-and-a-half years that you’ve been at it. I guess better late than never to get expedited.
DOBLIN: Very true. Well, partially we did this through a non-profit, and so fundraising was a challenge and also developing our method. We had a lot of work to do. But there was a lot of resistance. It is sad how long it’s taken us.
LEVITT: We haven’t actually talked about what this treatment is and the intervention that we’re talking about is a combination of treating PTSD with therapy and the drug MDMA, which is better known as Ecstasy or Molly. I got to believe that the fact that the drug that works happens to be a party drug — and the organization that’s been pushing this is your group MAPS, which is short for Multidisciplinary Association for Psychedelic Studies — that those two factors have really complicated this greatly, compared to the traditional pharma company who develops a new molecule and then pushes it in the normal way through the F.D.A.
DOBLIN: You’re totally right about that. Although what most people don’t realize is that starting in the middle ‘70s to the early ‘80s, MDMA was a therapy drug before it was a party drug. Dr. Sasha Shulgin was the pharmacologist who helped bring the attention of therapists, particularly Leo Zeff, who we called the secret chief, the leader of the underground psychedelic therapy movement. And even though MDMA was legal, it was kept quiet as a therapy drug for fear that once word got out about it, it would be criminalized. But before word got out about it as a therapy drug, it escaped from these therapy circles and began being marketed as Ecstasy in public settings, in bars, particularly the Starck Club in Dallas and elsewhere. And that’s what attracted the attention of the D.E.A., the Drug Enforcement Administration. And MDMA was criminalized in 1985.
LEVITT: Now, there are a lot of critics. Let’s just start by saying there are a lot of critics on this topic. One of the assertions I’ve heard made is that this whole endeavor that you’ve undertaken for the last 37 years is just a ploy to make the drug MDMA easier to get for recreational usage.
DOBLIN: First off, I would say that recreational is a pejorative term. It implies that it’s frivolous, it’s reckless, it’s heedless, it’s dangerous, doesn’t have any lasting impact. None of that is always the case. But I think that the work going through the F.D.A. has to stand or fall on its merits. The F.D.A. has very rigorous standards for the quality of evidence that you gather, how you gather it. But what is true is that we believe that MDMA-assisted therapy should be a prescription medicine where the treatments are covered by insurance. And at the same time, we believe that the war on drugs and prohibition is counterproductive, and that MDMA should be legally available to people in similar ways to how we’re seeing cannabis legalization that is taking place. I prefer the word celebratory rather than recreational. But a lot of this quote “non-medical” use is actually therapeutic. I speak to people all the time who have taken MDMA in “recreational,” quote, context, and got in touch with difficult emotions, difficult traumas, feelings, and were able to make a lot of progress in working through their issues. One of our fundraisers for MAPS, he’s gay and during the 80s when AIDS was a death sentence and people were dying right and left, he said they worked through a lot of their trauma on the dance floor taking Ecstasy. He didn’t realize at the time that it had previously been a therapy drug. It’s true that we are interested in working through the F.D.A., but it’s not a ploy. It’s something that will ideally obtain F.D.A. approval and insurance coverage to get it to people who have a diagnosis of PTSD. Our longer goal is mass mental health and a spiritualized humanity. And what I mean by that is that people identify by their tribe — we see that more and more in America and elsewhere all over the world — or by their religion or by their gender or by their nationality or various ways that we subdivide ourselves. And then we often create these “us” and “them” dichotomies and then we’re able to so often dehumanize and discriminate and be racist about people that are different than us. Humanity also is burdened by incredible anxieties and fears that we see all over the world now about climate change, about authoritarianism, and so what we want to do is have parallel paths. The F.D.A. path through drug development has to meet all the F.D.A. standards. The policy change has to then be approved by the public and by policy makers.
LEVITT: So one of the most ironic concerns that I’ve seen raised in this context is that it’s highly unusual and suspicious for advocates, that’s you and MAPS, to work to get a new drug approved, rather than a pharma company — somehow implying that big drug companies are unbiased and you’re biased, even though it would seem almost the opposite. I’ve been around drug companies and they really, really want to get their drugs approved. And it’s interesting that instead of commending you and a nonprofit for going above and beyond to do something different, people are nervous that you did it.
DOBLIN: Yeah, I find that ironic as well. But that’s not an uncommon criticism. What I say to people is that everybody has their biases — as you noted, pharmaceutical companies to their shareholders, and wanting to get drugs approved. I said the response to that is scientific methodology. The whole purpose of scientific methodology is to try to reduce the impact of experimenter bias on the results that you obtain so that we try to get closer to what’s actually happening. Rather than having people attack me for the fact that MAPS is an advocate, I’d say, look at our protocol design. Give us advice on how we can improve the methodology. And we have negotiated this methodology with F.D.A. The F.D.A. and MAPS engaged in an eight-month process called Special Protocol Assessment. And so during the Special Protocol Assessment process, you negotiate every single aspect of your design, your statistical analysis plan, your methodology for dealing with the double-blind studies, your metrics, which ones you’re going to use, your treatment methodology, all the other ancillary safety studies that they want to see. Pharma companies wouldn’t do this because pharma companies don’t understand psychotherapy. And one of the best examples is the approval of ketamine for depression. And that was done by Johnson and Johnson through their subsidiary Janssen, and they approved ketamine without any therapy as a pharmacological treatment in and of itself to help with depression. But what therapists and researchers and clinicians have noted is that when you combine the ketamine with psychotherapy, the results are significantly better and they last longer. And that’s not good for the pharma company because then more money goes to the therapists. When the results fade very quickly, then you just need more ketamine. So if we would have waited for pharmaceutical companies to develop MDMA-assisted psychotherapy, we would still be waiting today.
LEVITT: Well, the other “problem,” in quotes, with MDMA is it’s old, right? It was developed back in 1912 by Merck, I think. It’s not on patent, so pharma companies can’t profit from it and therefore wouldn’t make the investment that you’ve made as a nonprofit.
DOBLIN: Well, there is a strategy for pharma companies to profit a little bit from this, rather than through patents. So, I learned about MDMA in 1982, and when I learned about it, it was called — Adam was the sort of code name for it as a therapy tool, but it had also just begun to be used as a party drug under “Ecstasy.” But when I learned about it, it had already been used to treat PTSD. And there were remarkable stories of people that had been able, through MDMA-assisted therapy, to overcome PTSD. So we didn’t invent the idea of MDMA-assisted therapy for PTSD. We started an anti-patent strategy that would try to block pharma companies — or ourselves — from patenting any of the myriad of uses of MDMA-assisted therapy. It turns out, though, that there’s a law that was signed by Ronald Reagan in 1984 and it was to provide incentives to develop drugs that were off patent. And the incentives are what’s called “data exclusivity,” which means that if you are a sponsor and you develop a drug that’s off patent into a medicine, no one can use your data for five years to market a generic. And not only that, but the F.D.A. cannot review the package of information about the drug from a generic manufacturer until the period of data exclusivity expires. Now, I did my Ph.D. at Harvard’s Kennedy School of Government on F.D.A. regulation of psychedelics, and I got my Ph.D. in 2001, and I completely missed this whole thing about data exclusivity. But for us, doing this initially through a non-profit, now we have the MAPS Public Benefit Corp., which is our for-profit pharma arm — the data exclusivity was enough. And even if we didn’t have data exclusivity, we would have done this because the healing potential of MDMA and other psychedelics is tremendous. And we weren’t doing this to rack up a bunch of dollars or have our stock price go up. We were doing it for the public benefit.
We’ll be right back with more of my conversation with Rick Doblin after this short break.
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LEVITT: Can you describe the actual interventions that you’re analyzing in these clinical studies on MDMA? What does MDMA-assisted therapy look like?
DOBLIN: Well, the MDMA-assisted therapy in our Phase 3 studies consisted of 42 hours of therapy. There’s three eight-hour MDMA sessions. So it’s completely unlike any kind of therapy that’s currently available. You don’t go to your therapist for eight hours in a row. But in our case you do. And there’s so much focus on the preparation and the integration. I would say that one of the main differences between quote “recreational” use and therapeutic use is that in recreational use people are just looking to have a good time and it’s about the experience itself. In therapy, what we’re doing is we’re trying to have long-term changes in problematic emotions, behaviors, sensations. And so we have a very strong emphasis on integration after the MDMA experience on how to build into long-term change from this acute experience. We have 12 90-minute non-drug psychotherapy sessions in addition to these three eight-hour long MDMA sessions. The MDMA sessions are roughly one month apart and the non-drug psychotherapy sessions are roughly one week apart. So we have three 90-minute preparation sessions before the first MDMA session. That’s to educate people about what MDMA does, and for the therapist to get a sense of the trauma history of the patient that they’re working with — and that’s to develop what’s called the therapeutic alliance. What people have noticed in psychotherapy outcome research is that the most important factor, as far as whether people get better, is not the school of psychotherapy. It’s not whether it’s prolonged exposure or cognitive-processing therapy or Freudian psychoanalysis or psychodynamic therapy. It’s the relationship between the patient and the therapist. And if they have a sense of safety and support, the therapeutic alliance is strong, and that’s the biggest predictor of therapeutic outcomes. And then we have three 90-minute, non-drug psychotherapy sessions for integration purposes after each MDMA session. So it’s about a three-and-a-half-month process. It’s very labor intensive. And they’re durable. If these results were not durable, then insurance companies wouldn’t pay for it because it is labor intensive at the very beginning.
LEVITT: I don’t know much about therapy or mental health interventions, but anytime you can have a short-term intervention that yields long-term dividends, that seems rare to me.
DOBLIN: Well, first off, I don’t want to give the impression that it’s durable for everybody. Some people do get re-traumatized and might need more therapy. But in our Phase 2 studies, people kept getting better, on average, after the therapy was over. But what I think really helps us understand why it is that there can be an acute short-term intervention that has long-term outcomes is this process of neuroplasticity. There’s an incredible scientist, Gül Dolen, a neuroscientist at Johns Hopkins. And she’s done studies in a variety of animal species and has talked about how after a psychedelic experience — and she’s done this also with MDMA, with psilocybin, with other psychedelics as well — that there’s a period where the brain can be rewiring itself. So it’s called synaptogenesis, where there’s new synaptic connections made. And the psychedelics seem to have this fairly unique property of opening up these critical periods where people’s brains are more fluid. What we’ve seen with some small studies, fMRI studies, before and after patients are treated with MDMA therapy for their PTSD, that there’s reductions of activity in the amygdala, that there is more activity actually in the hippocampus for long-term memory storage. There’s more activity now in the prefrontal cortex. And the way in which memories of trauma are recalled, are routed in the brain differently after therapy. There’s also this idea of multi-generational trauma. There’s a woman that we work with, Rachel Yehuda, at the Bronx V.A., and she’s done studies on the epigenetics of trauma, and has demonstrated that there are markers that are passed on. She’s done work with Holocaust survivors and their children. And so what she’s doing right now at the Bronx V.A. is going to be studying epigenetic markers for people that are administered MDMA-assisted therapy inside the Bronx V.A. And it does seem in some early preliminary research that there may be a way to not only help people have durable remission of their PTSD symptoms, but also the changing, the disappearing, of some of these epigenetic markers that would then be passed on from generation to generation.
LEVITT: Cascading trauma.
DOBLIN: Yeah, and I think that the most important kind of theme over the last 30, 40 years — is that in the early ‘80s and into the ‘90s there was a lot of concern about MDMA neurotoxicity, this idea that it was going to be hurting the serotonin system and that there would be diminished connections between neurons. That narrative has not resulted in any convincing data. There was a major problem in the early 2000s where the leading team in MDMA neurotoxicity published a paper in Science that claimed that MDMA hurt dopamine and it would cause, potentially, Parkinson’s. And Alan Leshner, who was president of Science, put out a press release saying MDMA — taking it was like playing Russian roulette with your brain. It later came out that the researchers had mistakenly administered methamphetamine instead of MDMA.
LEVITT: Oh my god. That’s unbelievable.
DOBLIN: It’s one of the biggest mistakes in Science in general. But once that was retracted — the narrative has changed from neurotoxicity to neuroplasticity. And there’s what’s been called also “fear extinction” and “memory reconsolidation.” Memory is stored in different parts of the brain with episodic memory, emotional memories. And it used to be thought that when you would remember something, it’s like taking a book off the shelf and then you remember and then you put the book back on the shelf. But it turns out that in this memory reconsolidation process, you have a memory and then you have to recreate this memory, sort of rewriting the book. And that’s how people’s memories change over time, often with ways that we more want to remember things happening than they actually did. But this memory reconsolidation process has profound effects for PTSD because by processing the emotions in a therapeutic setting and by being able to release all those fears and anxieties and the body tensions, you have reprocessed the memory so that when you remember the trauma again after the therapy, it’s placed in the past. It’s not like it’s about to happen. And you’ve survived and you have been able to work with it. And so the memories — they don’t disappear for the trauma, but they don’t trigger the same kind of fears and symptoms that they did before. And I think the durability of the results is due in large part to the integration process that anchors the progress that was made during the MDMA session into brain changes and long-term changes.
LEVITT: And one reason why it seems sensible that MDMA would work is that when people do fMRI studies of people who’ve taken MDMA, you see the exact opposite pattern of what you see in PTSD patients, right? The amygdala, the activity gets greatly reduced, and the frontal cortex elevates, right? Is that correct?
DOBLIN: That’s exactly right. MDMA seems to do the opposite in the brain that PTSD does. So yeah, it reduces activity in the amygdala, so that fear-based memories no longer are so fearful. Activity in the prefrontal cortex is increased, so now you can think logically. And connectivity between the hippocampus and the amygdala is increased, so that memories can be moved out of this short-term, always about to happen or happening, into long-term memory. MDMA also releases a series of neurotransmitters, but also hormones, in particular oxytocin. And so the researcher that I mentioned before, Gül Dolen, she did a study in mice that showed that MDMA releases oxytocin, which is the hormone of love and connection and nursing in mothers, and it promotes what she called this “opening of the critical period” for social reward learning. But it also promotes new neural connections — this synaptogenesis as mediated through MDMA, through oxytocin — and then you develop these new neural connections in prosocial areas of the brain. We do think that this is the psychotherapy of the future. In many cases there will be new treatments developed — not just with MDMA, but with psilocybin, ketamine, — this idea of not just treating symptoms, but trying to get to the root cause of the problems and help people negotiate with them so that they learn from those experiences and then put them in the past and can move forward, that I think is going to be a very important future for psychiatry and psychotherapy.
LEVITT: I’d love to talk about the actual research design, because I think this combination of a drug along with therapy — it raises really interesting questions about the design and interpretation of randomized trials. Because traditionally studies are designed to be double blind, that neither the patient being treated nor the researcher knows whether the patient has been given the drug or a placebo. But my strong hunch is that with MDMA, both the patient and the therapist have a very good guess as to whether it was the actual MDMA dose or a placebo that was given. That’s true, right?
DOBLIN: That is very true. Around 90 percent of the people who get MDMA are pretty certain they got MDMA. There’s a little bit more confusion in the people that get the placebo because they’re there to work on their issues. They’re in this eight-hour session. And so there’s occasional confusion where people think maybe they got MDMA when they really got the placebo. They’re not quite sure. But the double-blind methodology is good, in theory, for reducing experimenter bias. However, in practice, even with S.S.R.I.s for example, there are different side effect profiles. So if you’re in a study, you get either S.S.R.I. or placebo, a lot of times the researchers can tell what group the people are in based upon the side effects that they talk about or how their emotions change. What we basically said to the F.D.A. was that, the real question is: if you can do this with therapy, why bother to add a drug? So we should really compare therapy at its most effective versus therapy plus MDMA. And that would be our recommendation.” And what they decided to do was to require us to do therapy with inactive placebo compared to therapy with MDMA.
LEVITT: So what the critics say here is your studies — because they’re not really blinded, because it’s so difficult to blind — they’re detecting a combination of any true impact of MDMA therapy plus whatever placebo effect there is. And maybe people just got better because they believed that treatment should work. Now, my response to that, which I don’t think is the quote “accepted rigorous scientific consensus,” is: who cares? If part of the reason that MDMA therapy works is because people believe in it, then that’s fantastic. The placebo effect is a wonderful ally in our fight for mental health. Why not take full advantage of it?
DOBLIN: I totally agree. Not only that though, if they’re saying that it’s because people believe it will work and that’s contributing to them getting better, the belief it will work is going to be even stronger after F.D.A. has approved it.
LEVITT: Exactly. Yeah, absolutely.
DOBLIN: I think that the critics are right in the sense that there is this expectation that people have, or hope, that it will work. And because we’ve published our first Phase 3 study results in Nature Medicine in 2021 — and Science at the end of the year looks at ranking, what are the top 10 scientific breakthroughs in the world, and they chose our paper. But what it indicates is that there is now a growing sense that we are developing really strong data and we’re publishing the results of our second Phase 3 study very shortly. By the time this comes out, it will have been published, and people will see that we have — in the most rigorous way that the F.D.A. could require us to do — generated remarkably statistically significant results with excellent safety profile. There’s loads of people that need healing from PTSD that they’re not able to get from currently available medications. And when the double blind fails, the solution is not to just throw away those drugs for which the double blind fails. It’s how do we still do the research? How do we get these treatments to people? And the other reason that we use inactive placebo in the control condition is that then we have a better sense of the actual safety database. Now we can say that in people that have severe PTSD, which is our first Phase 3 study requirement, going through therapy is risky because it brings up the trauma that people have tried to suppress and it can be very re-traumatizing. It’s not because of MDMA.
You’re listening to People I (Mostly) Admire with Steve Levitt and his conversation with Rick Doblin. After this short break, they’ll return to talk about why Rick had a pet wolf.
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We’ve talked almost exclusively about the clinical trials that have proven MDMA is an effective treatment for PTSD. But Rick’s perseverance into this field is tied to a bigger worldview that I’d like to unpack.
LEVITT: So I think it’s fair to say that if and when MDMA gets approved, everyone will agree that without your efforts over the last 37 years, it never would have happened. And with success so close now, the whole journey you’ve been on seems completely sensical and logical. But honestly, if we could magically transport ourselves back to 1986 when you started MAPS, I’m sure that I would have said that you were completely delusional, a dreamer, grandiose ideas, absolutely no chance of achieving them. Did you even realistically think you were going to pull this off?
DOBLIN: No, I didn’t think it would succeed either. This was the height of Ronald Reagan and Nancy Reagan and escalation of the drug war. MDMA had just been criminalized. But I thought that the argument had to be made. And what really animated me — and this will get back into kind of the spiritual, political aspects of psychedelics in general — but I really focused my life on psychedelics back in 1972, so 51 years ago, and that’s when I was just 18 years old. And I had just read a book by Stanislav Grof, who was the world’s leading LSD researcher at Hopkins. His research was being just shut down after the backlash against the psychedelic 60s. And his book was about the therapeutic use of LSD, but it was called Realms of the Human Unconscious: Observations from LSD Research. And it was a scientific lens, but he talked about things that he later developed into what’s called “transpersonal psychology,” things that we all share — confrontation with death, larger issues of unitive mystical experiences, things like that. And through my own LSD experiences as a 17 and 18 year old, I also had intimations of this sense that you hear from a lot of people about how we’re all connected. It’s all connected. I felt very traumatized growing up, secondarily traumatized — I’m Jewish — by stories of the Holocaust. I was a young boy during the Cuban Missile Crisis, and we had all these stories about how if there’s a nuclear war, just duck under your desk and you might be fine. For a little boy, 10-year-old boy, that was terrifying to think that there could be a nuclear war and we could all go up in flames. And then, even my own country, where I was concerned about Vietnam, I was totally appalled by the degree of human cruelty. Jung talked about how one of the most important things that we can do, both therapeutically, spiritually, and politically, is to withdraw the projection of our shadow onto others — meaning the parts of ourselves that we disown, that we don’t like, we put out on other people and they become all bad. And so my sense as an 18 year old was that this sense of unity, the sense of how we’re all connected, could be the antidote to genocide, to racism, to sexism. And since it had just been all squashed, I thought, okay, this would be something good for me to work on. I will try to bring psychedelics back in the hopes of consciousness change. And so in my early 20s, I had a dream of a Holocaust survivor on his deathbed telling me that he almost got killed during the Holocaust, but he was saved for a purpose, but he didn’t know what the purpose was. And now all these years later, he’s on his deathbed — and this is, again, me in my dream — and he’s telling me, “Now I know my purpose is to tell you to study psychedelics, and to bring back psychedelics so that people can experience this unity, and that might help us stop killing each other and destroying the planet.” I just felt like I have to do this. And no matter how much opposition there is, I’ll continue no matter what.
LEVITT: Just to put things into perspective, it wasn’t like you were a big player in 1986. You were 33 years old. You were still a year away from getting your undergraduate degree, having taken roughly a decade’s leave from the New College of Florida. Along the way you’ve done a great deal of experimenting with psychedelics. You built houses for seven years. You even had a pet wolf, of all things. And I know it’s got nothing to do with anything, but how did you end up with a pet wolf?
DOBLIN: Phaedrus was his name.
LEVITT: Zen and the Art of Motorcycle Maintenance?
DOBLIN: Exactly! I was 21 years old and I was looking for a dog. And I wanted a big dog that I could run with and wrestle with, like a German Shepherd or something like that. And then a friend of mine contacted me and she said she saw an ad in the paper from the Humane Society saying that they had shut down a wild animal breeding operation. This is Sarasota, Florida, which was the winter home of the Ringling Circus and a lot of carnivals were there. And so they had shut down this wild breeding operation and the female wolf was pregnant and had a litter of eight wolf cubs. And the zoos were full, the sanctuaries were full, they didn’t know what to do with them. And so they wanted to see if anybody else would help them take care of them. I thought, “Oh my God, this could be incredible.” I was very shy at the time and very insecure. And so when I went to the Humane Society, I said, “If I am going to take a wolf, I’d like to take the most dominant of the litter. Because I feel like I could learn some skills from confidence from this dominant wolf.” And wolves are born with their eyes closed. It takes a little bit of time for them to open their eyes. And they were taken away from their mother and bottle fed by humans, and so these wolves opened their eyes on people. They were an unusual group of wolves. And I managed to get Phaedrus when he was only eight weeks old. And I had him for about two years. I built this house when I turned 21. And where I lived was the classic edge of town. Right across the street was railroad tracks, and beyond the railroad tracks was out in the county. And that was undeveloped land, hundreds and hundreds of acres. So I was able to take Phaedrus and run with him off the leash through the woods. And I learned so much from him. There was this confidence that he had being the apex predator. Most dogs didn’t like him, didn’t want to play with him. He smelled different. The other thing I learned from this wolf was that it’s a lot like psychedelics. You know, psychedelics, we demonize them. And wolves have this reputation for being these fearsome, horrible animals that kill people all the time. They don’t actually kill people. They don’t hunt people. They’re the repository of fears, but they’re actually wonderfully loving animals. This wolf never hurt me. There was one time that the wolf challenged me for dominance. This was after I’d given the wolf away. The woods that I used to run with Phaedrus in started getting developed and so I didn’t feel like he could really have this free-roaming, wolf-like life. And a space opened up in a wolf sanctuary with a female wolf that wanted a mate. And I would visit him every couple of months. That was up near an hour outside of Washington, D.C. I was down in Sarasota, Florida. So it was a big thing for me to go up there and visit him. And when he was around four, around the time that in the pack they’d be coming into their maturity, I went to visit him and take him out for a walk. And the person that had the wolf sanctuary, his name was Ruffin Harris, had a glove and a chain-link leash. And he went to get Phaedrus. And then when I start petting him, he’s not welcoming my touch and I feel there’s something wrong here. And so I think, okay, I’ve got to reassert my dominance. I stood six feet away. I stared down at him and thought that would intimidate him, and then we’d go out for this pleasant walk. Phaedrus’s eyes just glazed over, — almost like he was looking through me. I saw a ripple go through his body of his muscles. And I thought, “This isn’t working well,” and then he leaped — and he leaped so fast and so strong that he pulled the chain leash out of Ruffin’s gloved hand, and he’s coming at me right at my head. This used to be the way we would wrestle and play all the time. His goal was to push me over, my goal was to try to flip him over on his back. And I tried to push his jaw away, but he managed to get my wrist in his jaw as he’s sailing through the air by my face. And he crunches down on my wrist and he just looks at me and then lets go. He was like, “Tag, you’re it. If this goes further, I might have to hurt you, but I don’t want to.” So that was the last time I was ever able to be with him. And that night I was crying and I was sad and I called my parents to tell them what was happening. And my dad surprised me. He said, “What’s the problem? You did it to me.” I’m like, “Whoa, you’re so right. I did. And I’m glad I did.” I dropped out of college to study LSD. That was not my parents’ plan for me when I was 18. And so I became more comfortable with this idea that now Phaedrus was his own wolf. And that even though I could never visit him again and play with him, take him out for a walk, he was coming into his own.
LEVITT: Does the fire still burn in you? You’ve worked so hard for so long on psychedelics. Are you ready to hand the struggle over to the next generation? Or are you still going strong?
DOBLIN: I’m still going strong. And the fire burns in this way — so for almost the entire history of MAPS, the goal was: make MDMA into a medicine. Now that it looks like that’s likely to happen, we needed a new animating vision, and also a new multi-generational vision. So I’ve reformulated what we’re after and now the new vision is a world of net-zero trauma by 2070. Net-zero trauma doesn’t mean no trauma. There’s a prediction that by 2050, if climate change isn’t mitigated, there could be a billion climate refugees. There’s a rise of authoritarianism. And we do see ever increasing repression in Russia and China and North Korea and elsewhere. So there’s a lot of trauma that’s going to be increasing. So net-zero trauma means that we don’t add to the burden of trauma on humanity as a whole. And then we can start trying to reduce the total burden of trauma. And so what MAPS is doing now is we just had a training in Sarajevo. It was for Ukrainian therapists. We had Bosnian, Serbian, Armenian, Polish, Lebanese, Italy, and also the Czech Republic. So we’re starting to focus on humanitarian projects, on globalization of the healing potential of MDMA-assisted therapy for PTSD. And what’s so exciting about it and what’s so difficult is that in many countries that have been very traumatized, they don’t have a lot of psychiatrists and psychotherapists. And so we’re going to have to be exploring new group therapy methods with local healers. I’d like to plant some seeds in that direction. And that’s where the fire exists for me, to start processes that I know I will not be alive to see the full fruition of, but that I think move beyond just the medicalization of MDMA. So, the fire definitely burns still.
My God, that wolf story! I’m so glad I asked. I didn’t actually think the question would lead anywhere. And I certainly didn’t expect a story like that. My goal before I started this conversation was to understand what makes Rick Doblin someone who can not only dream big, but turn those dreams into reality. A few things stood out to me. First, he had absolute mastery of the science and the research design issues. I think many dreamers don’t have the talent or the interest to become experts about the details. Second, for better or for worse, he seems to be driven by deep principles and beliefs, rather than by weighing costs against benefits. I mean, who drives halfway across the country to visit a wolf? Economic thinking would say that cost benefit analysis is absolutely the right approach. But I’ve seen a lot of successful people violate that rule. And I think sometimes you can get better results by ignoring short-term cost versus benefits. The third thing about Rick is he had great judgment in picking a problem where the science was on his side. If the results of those studies hadn’t been so stunning, he wouldn’t be on the verge of succeeding. But let’s not lose sight of the fact that I’m only talking to Rick because he succeeded. There might be a hundred Ricks out there pursuing big dreams with immense talent and creativity, but who fail. The academics call it survivor bias. And if you only study those who succeed, you can really get misled. It’s definitely not a mistake to admire Rick for what he’s accomplished and the way he did it. But it might very well be a mistake to devote your life to trying to be the next Rick Doblin.
LEVITT: So now’s the time when we take a listener question. And as always, I’m joined by my producer, Morgan.
LEVEY: Hi, Steve. So we had a listener named Jeff write in, asking if there was any interesting research you’d come across lately. It’s an interesting way to check in on what you’re reading and hearing about. So, has anything caught your eye in the academic community?
LEVITT: Yeah, there actually was a fascinating paper I came across just recently by Eyal Frank of the University of Chicago and Anant Sudarshan at Warwick University. And this is a paper that sounds totally preposterous on its surface, but it comes to a remarkable and unexpected, but ultimately plausible conclusion.
LEVEY: Okay, so what’s it about?
LEVITT: It’s about vultures.
LEVEY: The bird?
LEVITT: The bird! Vultures, the bird! Believe it or not. Okay, so in India, in the 1990s, farmers started treating their cows with an anti-inflammatory drug that was harmless to cattle and humans, but it was completely toxic to birds. It caused kidney failure and death within just a few weeks. And over the course of the 1990s, the population of vultures plunged by 90 percent in India.
LEVEY: Why would any academic pay attention to this?
LEVITT: Well, it turns out that 30 million cows die a year in India. If you’re ever in India, there are cows all around, and these cows are often in urban settings. Well, vultures eat the dead cows. They’re really good at it. They devour a dead cow within 40 minutes.
LEVEY: Forty minutes for a whole cow?
LEVITT: That’s what they say in the paper. So when vultures are gone, these carcasses, they just sit and rot and rats and feral dogs eat them and they potentially become a source of disease. Okay, so does it really matter? The researchers did a really simple but compelling analysis. It’s what economists call differences in differences. And it’s really simple. Absent a randomized experiment — so we aren’t randomizing where the vultures get taken away — they do a comparison of areas that were hospitable to vultures before the vultures all died compared to areas that didn’t really support vultures anyway. So they look before and after the vultures die. So in the places where there were a lot of vultures before, there aren’t so many after. In the places where there weren’t very many vultures to begin with, there still aren’t very many vultures there after. And they take the difference in the difference. And they basically use that as a sort of natural experiment to see whether or not the disappearance of these vultures has any impact on human health.
LEVEY: Okay, so I’m going in blind here but I’m going to guess it had a huge impact on human health.
LEVITT: Well, you would have been right, and I would have been wrong, because when I started this paper, I could not really imagine that vultures had anything to do with human health. But by the researchers’ estimates, there are an extra 100,000 human deaths per year —
LEVEY: Oh my god!
LEVITT: — because the vultures were taken away. That’s every year, 100,000 human deaths. This is one of the biggest impacts on life I’ve ever seen of any economics paper anywhere. And the vultures seem to be at the heart of it. What I find so incredible and so interesting is there’s a lot of research done in the area of conservation and climate change and whatnot, but this paper, if correct, is one of the clearest, most interesting, most explainable examples of how what we do to nature really matters. And matters in ways that we really can’t anticipate ahead of time. I just find it to be a really compelling piece of research.
LEVEY: That’s an amazing paper. We will put it in our show notes. If you have an interesting bit of research you want to share with us, or a question, our email is PIMA@freakonomics.com. That’s P-I-M-A@freakonomics.com. It’s an acronym for our show. We read every email that’s sent and we look forward to reading yours.
And in two weeks, we’re back with a brand new episode featuring Abraham Verghese. Not only is Abraham a highly respected and influential physician at Stanford University, he’s written a series of blockbuster New York Times bestselling novels. How in the world does one person manage to do both of those things? I hope we can find out.
VERGHESE: One of the lessons that my patients were teaching me was, don’t postpone those things that you really feel a burning desire to do, because life’s too short. And I wanted to tell their story.
As always, thanks for listening and we’ll see you back soon.
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People I (Mostly) Admire is part of the Freakonomics Radio Network, which also includes Freakonomics Radio, No Stupid Questions, and The Economics of Everyday Things. All our shows are produced by Stitcher and Renbud Radio. This episode was produced by Julie Kanfer and Morgan Levey, with help from Lyric Bowditch, and mixed by Jasmin Klinger. Our theme music was composed by Luis Guerra. We can be reached at PIMA@freakonomics.com, that’s P-I-M-A@freakonomics.com. Thanks for listening.
DOBLIN: Phaedrus walks up to this Doberman and this Doberman just gets up and runs away. I could get my LSD stash and I could trip that day.
- Rick Doblin, founder and president of the Multidisciplinary Association for Psychedelic Studies (MAPS).
- “MDMA-Assisted Therapy for Moderate to Severe PTSD: A Randomized, Placebo-Controlled Phase 3 Trial,” by Jennifer M. Mitchell, Marcela Ot’alora G., Bessel van der Kolk, Scott Shannon, Michael Bogenschutz, Rick Doblin, et al. (Nature Medicine, 2023).
- “MDMA Therapy Inches Closer to Approval,” by Rachel Nuwer (The New York Times, 2023).
- “Psychedelics Reopen the Social Reward Learning Critical Period,” by Romain Nardou, Edward Sawyer, Young Jun Song, Gül Dölen, et al. (Nature, 2023).
- “The Social Costs of Keystone Species Collapse: Evidence from the Decline of Vultures in India,” by Eyal Frank and Anant Sudarshan (SSRN, 2023).
- “Global Health, Climate Change and Migration: The Need for Recognition of ‘Climate Refugees,'” by Saverio Bellizzi, Christian Popescu, Catello M. Panu Napodano, Maura Fiamma, and Luca Cegolon (Journal of Global Health, 2023).
- “Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among U.S. Veterans,” by Paula P. Schnurr, Kathleen M. Chard, Josef I. Ruzek, et al. (JAMA Network Open, 2022).
- “MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study,” Jennifer M. Mitchell, Michael Bogenschutz, Alia Lilienstein, Charlotte Harrison, Rick Doblin, et al. (Nature Medicine, 2021).
- “Inner City Blues: Children Raised in Inner-Cities Face Comparable PTSD Causing Conditions and Consequences as Military Veterans and Deserve Our Attention,” by Eric Citizen (SSRN, 2019).
- “Intergenerational Transmission of Trauma Effects: Putative Role of Epigenetic Mechanisms,” by Rachel Yehuda and Amy Lehrner (World Psychiatry, 2018).
- “Durability of Improvement in Post-Traumatic Stress Disorder Symptoms and Absence of Harmful Effects or Drug Dependency After 3,4-Methylenedioxymethamphetamine-Assisted Psychotherapy: A Prospective Long-Term Follow-Up Study,” by Michael C. Mithoefer, Mark T. Wagner, Rick Doblin, et al. (Journal of Psychopharmacology, 2013).
- “RETRACTED: Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (‘Ecstasy’),” by George A. Ricaurte, Jie Yuan, George Hatzidimitriou, Branden J. Cord, and Una D. McCann (Science, 2002).
- “Why Aren’t All Drugs Legal? (Replay),” by People I (Mostly) Admire (2022).
- “Can the Big Bad Wolf Save Your Life?” by Freakonomics Radio (2022).
- “How Are Psychedelics and Other Party Drugs Changing Psychiatry?” by Freakonomics Radio (2020).