The Path Ahead for MDMA-Assisted Therapy - Dr. Michael Mithoefer, Clinical Investigator at MAPS Public Benefit Corporation

Shiv Gaglani: Hi, I'm Shiv Gaglani. Of the many hopeful developments in psychedelic research in recent years, perhaps the most important is that FDA approval of MDMA for treating post-traumatic stress disorder appears likely within the next twelve months. My guest today on Raise the Line, Dr. Michael Mithoeffer, is a leading figure in psychedelic-assisted therapy who spearheaded clinical trials of MDMA-assisted therapy for more than twenty years, leading most recently to the completion of successful Phase III trials treating PTSD. 

He is also a senior leader at the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation (MAPS), which has led this groundbreaking research. He and his wife, Annie, completed the first MAPS-sponsored Phase II clinical trial testing MDMA-assisted psychotherapy for crime-related PTSD and subsequent studies with military veterans, firefighters, and police officers, as well as a pilot study treating couples. He has been medical monitor for a series of Phase II trials which produced data that led to FDA breakthrough therapy designation. 

I recently met Dr. Mithoefer at the Psychedelic Science 2023 conference in Denver, and I'm looking forward to continuing our conversation about the current and future state of psychedelics as a treatment modality. So, Dr. Mithoefer, thanks for taking the time to be with us today. 

Dr. Michael Mithoefer: Thank you, Shiv. Good to see you again. That was a wild time in Denver, eh? 

Shiv: Yeah, right before we hit record we were talking about how I just published this recap of Psychedelic Science in Forbes a couple days ago, and I think the best way to describe it in my mind is the ‘Society for Neuroscience conference meets Burning Man.’ I'd actually love your take on it. Maybe let's start with that before we go into your background. How have you decompressed or integrated since that conference? 

Dr. Mithoefer: Well, you know, it's always been a feature of MAPS that they've been interested in things like harm reduction and drug policy, on one hand, at the same time as doing really rigorous research, and now the research has been handed off to the subsidiary, MAPs Public Benefit Corporation. But the main thing I meant by wild time was how many people, more than 12,000 people showed up, and they had to turn people away, and just looking back at our first psychedelic science conference in San Jose many years ago, we had 800 people or 900 people, I think. So, it's a sign of the times. I think actually the ratio of hard science and clinical research to other interests in psychedelics was actually higher this time. There was even more scientific research presented than in the beginning. So, I thought it was quite amazing to have that many people interested in this and a lot of serious clinicians and researchers. It's a sign of how far this field has come over the last twenty years. 

Shiv: Yeah, absolutely. I was very impressed with the people I had met and the speakers. You had the NIMH director, who's going to be on the podcast in a couple of weeks, as well as the CEO of Burning Man Project. So, you had all up and down the spectrum. 

Dr. Mithoefer: And the governor of Colorado. 

Shiv: And, yeah, both the governor of Colorado and the former governor of Texas. So, bipartisan support for the work you guys have been leading. I'm sure it felt a bit like the desert for many years in the beginning, but we'll get right into that, too, because I'd love to hear your take, having been leading this work for so long. 

So, before we go into that, given that so many of our audience are early-stage healthcare professionals, I think they'd be interested in hearing about your background. What got you interested in medicine? And then when you were in med school, why did you choose psychiatry?

Dr. Mithoefer: Well, I didn't choose psychiatry when I was in med school. I chose internal medicine, which was my first residency and then I actually practiced emergency medicine for ten years. And then in 1991, I was getting more and more interested in what was going on before people arrived in the emergency department, and so much of it was psychological challenges leading to trauma, violence, overdoses, diseases of lack of self-care, that kind of thing. 

So, in ‘91, I went back and did psychiatry residency. That's what kind of drove me in that direction, partly being more interested in what the antecedents of the problem was, but also, I really felt interested in a different way of working with people. You know, in the ER, it was very useful that I was doing things to people all the time...putting tubes in to make them breathe or that kind of thing. But over time, I longed for a more collaborative relationship to kind of work with people on these issues. So, that's why I went into psychiatry and actually, well, when I was looking for where to go with my career, I read a book by Stanislav Grof, who was one of the early premier LSD psychiatrists from Prague and then Johns Hopkins and it was actually reading Stan Grof's compelling reports of all his work with psychedelics in a serious medical way before they were illegal, that I thought that was very much in line with what I was interested in. 

So, I kind of went into psychiatry originally with an interest in this idea of how do you shift consciousness for the purposes of healing and growth? 

Shiv: Wow, that's fascinating. I didn't know that back story and, you know, before we go into once you've finished as a psychiatrist and how you got into psychedelic research, you know, I've gone back to med school after a career in education entrepreneurship, and it's been quite an adjustment. I'm curious, after having a successful practice in internal medicine, emergency medicine, how did it feel going back to residency as a psychiatrist, day one. You know, were you hazed at all? And how was that?

Dr. Mithoefer: Oh, it was pretty annoying. I had to get up in the middle of the night all the time and go admit patients and be a resident again. But at the same time, it was exciting because I was learning so many new things. 

Shiv: Yeah, no, that's great. And it's definitely a theme we've had on this podcast of people who've had so-called non-traditional or zigzag careers and I always have a lot of respect for people who, you know, are willing to do that and it takes a lot of putting the ego aside and starting again and not buying into the sunk cost fallacy. 

So, you've become a psychiatrist, you've already gone in with this interest in consciousness and Stan Grof's work. Can you walk us through what happened leading you to joining MAPS and getting involved in MDMA research?

Dr. Mithoefer: Yeah, well, when I went to psychiatry residency, I also enrolled in the Grof training. Stan Grof has a training in -- not in LSD anymore because that's not legal -- but in using holotropic breath work as another technique for shifting consciousness in a very similar way. So, I was doing them simultaneously, which is very interesting -- going to California a couple of weeks at a time and getting the training and the breath work and transpersonal psychology, and then coming back to the Institute of Psychiatry at the Medical University of South Carolina and seeing the contrast. So, I came out of that thinking, well, we can't do it with psychedelics now, but the breath work is very powerful, which it is. It's really, I think, quite comparable in many ways, but obviously different. 

So, my wife, Annie, who's a nurse, went and did the training with Stan later and then when I started my psychiatry practice, we started doing holotropic breath work groups every month and there was a lot of back and forth. People would come to the breath work, and then they might want to come do some individual work in the office, or they might come see me as a patient in the office and then decide, you know, they'd like to try breath work. So, our practice together was very much informed by Stan Groff's ideas and by an interest in not just talking about things -- we did talk about things -- but having a shift of consciousness to maybe allow something new to happen. So, for ten years, we assumed that we had to do it just with breath work. 

Over time, I became more and more impatient with the fact that we weren't even investigating these other possibilities. I never really intended to be a researcher, although I've been one for more than twenty years now. I was kind of forced into it by the need of the patients we were seeing. You know, people are showing up suffering, and we had reason to believe these other tools might be helpful, and it just didn't seem even ethical not to be investigating them at least. So, that's kind of why we went in the direction. 

I knew about MAPS from when I was in the breath work training. So, I figured Rick Doblin was the person to ask. Well, at first, I thought I'd have to go to an offshore island nation or something to do the research and that's how I approached Rick in January of 2000. And he said, you can do it here, and we'll help you. So, Rick and I have been working on this ever since then, and he was working on this many years before that.

Shiv: Yeah, I know. We had Rick on the podcast a couple months ago, actually, right after your second phase three successful clinical trial was announced in January. And yeah, obviously, an incredible story of working on this for forty years, getting a PhD at Harvard to do this.

Dr. Mithoefer: Oh, talk about commitment.

Shiv: Yeah, exactly. So, one thing Rick talked about was being in this desert for a long time, right? Being that crazy one or the one who's not accepted by the traditional medical community and there's a lot of pioneers in medicine who have had to face that. Obviously, sepsis treatment or another one that comes to mind is the Nobel laureate who discovered H. pylori causes gastric ulcers. His colleagues thought he was crazy. 

When we met at the Psychedelic Science Conference a couple of weeks ago, you did mention not being accepted in the academic community. I'd love to hear -- for our audience, some of whom may be in positions where they aren't understood by their colleagues or peers when they're trying to innovate and do the right thing for their patients -- I'd just love to hear that story, if you can share it, as well as any sources of perseverance and persistence that you drew upon to keep doing this work for as long as you have to get to the point where now we have 12,000 people and tons of published papers about it.

Dr. Mithoefer: Yeah. Well, it's been an interesting journey. At first, it was very controversial and, you know, most people in academia wanted nothing to do with it. First we thought we were going to try to do the research at the medical school and the research center, but then it became clear they didn't want it to happen there. So we got permission from FDA to do it in our office. But then when my clinical faculty appointment came along, it was not renewed. There were people on the committee who just thought they should have nothing to do with anything like this. So that went on for quite a long time. Ironically, a few years ago, the same medical school, Medical University of South Carolina, asked us to help them with their developing a world-class psychedelic research treatment and training center. So, that's a huge shift. 

For many years, it was hard to get anybody to take this seriously, or most people. Now it feels as if I'm trying to get people to calm down a little bit. It's great, but it's not magic. So, it's been that kind of a journey and I guess what kept me going is, well, it was an adventure. It was often frustrating -- many obstacles, many delays, years of delays, and kind of one obstacle after another -- but it was exciting because I felt, you know, this makes so much sense. It's got to happen eventually. On the one hand, it was frustrating. On the other hand...maybe I'm perverse enough to have felt -- and I think Rick and I both felt -- well, if we're causing this consternation in this system that isn't working very well in the first place, this medical system has a lot of problems, maybe we're on the right track, so just keep going. So, we were actually kind of emboldened by the resistance if anything. 

Shiv: Yeah, that's awesome. There's a great book by Nassim Nicholas Taleb -- who's written The Black Swan and Skin in the Game, among other great books -- Anti-Fragile is the book's name, and the whole concept is there are things or people who are fragile, right? They get stress and they break; there's things that are resilient, there’s stress and they maintain; and then there's things that are anti-fragile, there’s stress, and they get stronger. It sounds like MAPS and the work you and Rick have been doing for years, is sort of anti-fragile...the more the clamor against what you guys were doing was the more maybe faith you had in what you were doing, which is, maybe I'm projecting, but it seems like MAPS is an anti-fragile organization. 

Dr. Mithoefer: It did feel that way, yeah. 

Shiv: So again, we've culminated in this huge 12,000-person conference with tons of great research coming out of it. A lot of promise, a lot of hype. We can talk about some of the hype too. And as you said, it's not a magic pill that people can swallow. But where do you see it going now? I introduced you by saying maybe we're expecting FDA approval in the next year. What are some of the steps to actually get this to be a mainstream therapy?

Dr. Mithoefer: Well, it's a very interesting time in that regard, I think, because we don't know, of course, but it seems highly likely that MDMA-assisted therapy has a good chance of being approved for PTSD. So it's quite unique in that way. We're not talking about the FDA just approving a drug. It's a treatment package with a lot of therapy included with the drug. In fact, in our trials, MDMA is only taken three times, a month apart, with lots of therapy for preparation and support and then integration. So, I think now the question is going to be, if it's approved, how does it fit into this medical system we have, which I think is quite dysfunctional, especially with mental health? We've got lots of limitations and problems and our diagnostic system needs a lot of work. There's a lot to be learned in psychiatry, especially, I would say. 

So, I think there are already many discussions about, okay, if this is so successful, so effective for some people, and if it's approved, how does it fit into the session where we’re used to these short visits, and this is a much different approach? To me, the challenge is going to be not to try to distort the treatment to fit the system. Obviously, we need to figure out how to make it work from a practical point of view. I don't mean to not think about that deeply, but I think there's a real danger of missing the reality that this is quite different from the way we've been doing things, and it can't be necessarily fit neatly into the schedules we've been having. It involves much more therapy up front than other treatments because it's so concentrated. But we already have data from several health care economics papers, Elliot Marseille at the University of San Francisco has written a couple of those, showing with our data that this could be very cost-effective, it just takes a few years. 

So for one thing, there's going to be a challenge in the beginning. If there's a demand for this, it's going to tax the system more to find the time, a way to treat those people. If it pans out and it's as effective as our research results have suggested and is durable, then it may lighten the load on the mental health system eventually. But during that transition, it's going to be a challenge, I think and that's our next challenge. Because there are lots of pressures. 

We want to make sure it's accessible and everyone who needs it can get it regardless of ability to pay. That's a strong mission for MAPS and MPPC. So there's a lot of pressure to simplify, shorten, make it less expensive, which makes sense. But there's a real danger if people don't appreciate the importance of the support and the integration therapy, then I think that's going to be a problem because we do have data showing that this can help people a great deal in our trials, at least. I also think there are risks. I mean, I know there are risks, like any treatment, but I don't want to underestimate the importance of proper preparation and support during the sessions and help integrating afterwards to maintain the safety record that we've had. 

So I think that's going to be the problem. It's great to make it more cost effective. There are lots of ways that we may do that. Group therapy may be part of it. We're hoping that there's going to be group therapy starting in Portland soon. So I think there are lots of ways to make it more cost effective, but we’ve got to beware of the danger of going too far in that direction and having it backfire.

Shiv: Yeah, that makes perfect sense. And it seems like a lot of the cost or challenges comes from actually just how many sessions one has to do with therapists and two therapists, right? I know one of the main things you've been helping with is training a lot of therapists in

the protocols. Maybe you can comment on that and, like, what makes a good therapist? Many of our audience may be interested in getting this certification at some point. How are you thinking about scaling that out? We have maybe clinician extenders...I know chaplains have been shown to be a really good potential source of the right type of person to lead these therapy sessions or at least be the second observer or co-pilot. But obviously, we don't have enough psychiatrists out there and probably won't have enough psychiatrists to really scale this out directly. So yeah, I would love to hear your thoughts on that training aspect.

Dr. Mithoefer: Well, just to clarify the terms, we have trained a lot of the research therapists over the years. All the people that have worked on the research have had a rather robust training in our training program. In between the research and approval, we're not allowed to train anybody, but we are doing educational events to help people get educated about it, including practitioners. So, we don't know what that's going to look like exactly. 

I do agree that it certainly doesn't take a psychiatrist to do all this. There have to be prescribers, mostly physicians probably, who know about the medicine and can be responsible for the medical part. But there are other therapists and perhaps other people with appropriate experience who could be very good as support people. That's really a work in progress. That's one of the big challenges is to make sure if it's approved, the people or therapists using it are trained adequately and that we can train them as fast as possible without losing quality. We've experimented with some of the limits over the years. 

I'm convinced if we go too fast and it gets too big and impersonal, it's going to backfire. There are also ethical considerations. There's reason to think people are more vulnerable, you know, for ethical violations when they're taking these kinds of medicines, and maybe therapists are more vulnerable to thinking they're our saviors, and so they go off course. So for all those reasons, it's important to have really, really good training for therapists and build community and ongoing peer support and consultation, that kind of thing. There's a lot of thought and work going into what that's going to look like. 

MAPS and MAPS Public Benefit Corporation are going to want to increase their training program as much as possible. We're also very interested in collaborating with other groups that have the capacity to train people so that there are local and regional hubs of places where people can get training and ongoing supervision and ongoing communities to support each other as therapists. Also, I'm looking forward to the day when psychiatry residents and psychology graduate students get this training while they're in training. I'm hoping that'll be coming along too, and there are already some important universities working in that direction.

Shiv: Yeah, absolutely. I know at Hopkins, where I'm back in med school, Dr. Bit Yaden -- a psychiatrist we had on the podcast -- speaks highly of you. I think she has gone through your trainings and is helping set up some of that and getting more med students involved and hopefully psychiatry residents too. I know Berkeley has a center for psychedelics, and California has the Institute for Integrative Studies where a lot of training is done. Do you have any estimates of how many therapists we may need in the next decade, assuming this gets approved? 

Dr. Mithoefer: There are people at MAPS Public Benefit Corporation that have lots of estimates. I don't know what the latest are, but there's thought that we need thousands of therapists pretty quickly if the demand is what is expected. So I think that's going to be one of the limiting factors. How to get it paid for is going to be a challenge, but also how to have enough therapists. That's going to be difficult if we get approval and there are many people that want and need it, and we can't provide it fast enough. That's probably going to be the case, I'm guessing. But we need to really work hard on that, but not go too fast and lose quality, in my opinion. 

Shiv: That makes sense. Two follow-up questions on the training. I'm curious, what makes a good therapist in your opinion for this particular psychedelic-assisted therapy? That's question one. Number two is there's obviously a lot of activity in the underground -- like shamans, gurus, and others...some who are indigenous and some who are just people who took it upon themselves to help other people with protocols they've read about or maybe citizen science type work. We had Jim Fadiman on the podcast over a year and a half ago, and he's a big advocate for citizen science and engaging with that community. What are your thoughts on the underground and what we can learn from them, or maybe it's dangerous to have that going on?

Dr. Mithoefer: I think there's a huge overlap between what makes a good psychedelic therapist and what makes a good therapist in general. I think experience, the capacity to be curious and to have done enough of your own work so that when you get triggered by intense situations and sessions, you can manage that without being knocked off balance by it. When we do our educational events and our trainings, we're teaching people about the kinds of things that can come up in these sessions and ways to work with them. But we emphasize that the biggest part of it is them doing their own work in order to be present for these long sessions that can be very intense. I think that partly it's temperament for some people. The idea of sitting in the same session for eight hours sounds like a terrible idea for other people. You know, they have the inclination to want to be connected with people in that way. So, I think that people's general constitution and their amount of work they've done with their own emotional process in order to be able to stay present when it gets intense.

Shiv: Hmm. 

Dr. Mithoefer: As far as the underground goes, frankly, I've always been grateful that there are some really good, ethical underground therapists. There are also some not good, not ethical underground therapists, but that applies to above ground or underground. But I've personally been grateful that some people are willing to take the risk. I mean, a lot of the underground therapists -- I'm not aware of that many, but I know some -- you know, they were working with these medicines when they were legal, and they just were not willing to give up that tool with their patients. They were willing to take the real legal risk of continuing to work underground. So, I have admiration for the people that have done that well. 

One of the problems with things being underground is you don't know what's going on and some people, no doubt, are harmed by underground therapists, and there's no recourse or way to really address that. So, bringing it above ground is going to help with that. And also, it's going to bring its own challenges, too. 

Shiv: Yeah, absolutely and hopefully a lot more data so we can understand where this could go and the true scope of MDMA-assisted therapy and other psychedelic therapies. One of the genius things that I know Rick talked about when we had him on the podcast back in January was the focus on treating combat veterans who have severe PTSD with MDMA, because not only is there huge need given how much depression, anxiety, and ultimately suicide is in that population, but also it has strong bipartisan support. We obviously want to do what's right for our veterans who served our country. 

I'd love to hear about other populations and specific populations that you're currently working with or you're interested in working with. I mentioned in your bio, your couples work. I'm very interested in healthcare professionals who are burned out, have moral injury...how do we get them to heal and hopefully have high leverage and treat more patients over their careers? I'm also interested in founders and entrepreneurs, many of them who already are doing this in the underground. How can we help them be less stressed, make more socially conscious companies, etc. 

So, I'd just love to hear your take on other populations and protocols, maybe how we have to adjust those protocols for those populations, like the couples you're working with. 

Dr. Mithoefer: I guess there are two ways of thinking of populations. One is groups of people and the other is what is their problem they're struggling with. So, as far as the indication, the problem, the only thing we have a significant amount of data on is PTSD. We don't know about other possible indications, but there have already been some studies with end-of-life anxiety and social anxiety in people on the autism spectrum, things like that, and there's some more investigative trials coming along, including looking at eating disorders. Actually a couple of the MAPS therapists from New York are about to start a study with MDMA-assisted therapy for healthcare workers during COVID. 

Shiv: Oh, wow. That's awesome. 

Dr. Mithoefer: As a former ER doctor, I'm very interested in helping some of the healthcare people who carry a lot of stress and sometimes don't even know it. And then, you know, MAPS Public Benefit is required by law to submit a protocol for pediatric studies. They'll get a waiver for the six- to twelve-year-old, but there will be a study -- presumably, the planning is already in the works -- for twelve to eighteen. So, I think that's going to be a really interesting population to look at because a lot of people have so much trauma in childhood and people in our studies have said, ‘boy, I wish I could have had this kind of treatment twenty or thirty years ago, instead of all these decades of suffering.’ 

Shiv: Yeah, absolutely. That's super interesting. How about the couples work that I indicated? What's going on with that? 

Dr. Mithoefer: Well, before MDMA was illegal, there were lots of anecdotal reports, and some published case reports, about using MDMA with couples, and it seemed to be particularly helpful. Actually, my wife and I experienced that with a therapist back in the day. Many people report it really helps with communication, and people can drop defensiveness and really listen to each other in a much more effective way. So, I think that's an exciting area, and we really enjoyed that. 

The pilot study we did was only six couples, and we did it with Candice Monson and Anne Wagner from Toronto, who are both experts in cognitive behavioral conjoint therapy, working with couples with PTSD that way. So, we combined our method with their method, and, you know, it was just a pilot study -- so a lot more work to be done -- but it was exciting preliminary data and I personally really enjoyed working with people, because it was so gratifying to see them being able to communicate so much better. 

Shiv: Yeah, absolutely. I've definitely read those reports, and that's a very exciting avenue of research. We also had Bill and Brian Richards on this podcast from Sunstone Therapies. I know you know them, and they have a very interesting dyad study with psilocybin for end-of-life anxiety that includes cancer patients and their caregivers, because so much of the trauma experience or the anxiety or the sadness, really, the depression is experienced by the caregiver, not necessarily just the patient. 

Dr. Mithoefer: Yeah, yeah. I think it's very exciting. 

Shiv: You know, my understanding of psychedelic assisted therapy is you're only having one or two or maybe three sessions with the actual medicine, and then, you know, there's very impressive results at six months, twelve months, in terms of how long this effect lasts. Obviously, it's early days, so I'm not sure if there's, five-year, ten-year type of data or if that'll be monitored.

Part of my understanding of how these medicines work is that for that period of time while you're in the therapy and then doing integration, you're reframing perspectives. You're able to change your belief systems around those perspectives. The Michael Pollan analogy was it's like you have these moguls when you're skiing, these tracks that were embedded because they're icy now, these thought patterns, but because of these medicines, you're able to kind of have fresh powder deposited on the slope, and now you're able to form new thought patterns. 

That makes sense for things like smoking cessation, PTSD -- a reframe changing that -- but what about an ongoing chronic type thing? MDMA is an empathogen. Is there a world in which you think there's low dose MDMA that helps people chronically deal with stress, anxiety, or just be better, more flourishing humans? I don't know. That seems like the holy grail, but I'm just curious what your thoughts are on that. I mean, almost Aldous Huxley-esque with SOMA, I think, is one of the way to think about that, which he describes in Brave New World, but yeah, what are your thoughts on like long-term usage? 

Dr. Mithoefer: Well, if you mean long-term daily or frequent usage, is that what you mean?

Shiv: Yeah, I mean the therapy protocol is higher dose acute, and it'll have a long-lasting effect on a specific condition, but what about long-term use? Maybe not daily or weekly, but there's citizen science talk about microdosing. I don't know if people microdose MDMA, but, you know, how do people get to these states of being highly empathic long-term beyond just having a clinical diagnosis? 

Dr. Mithoefer: I've heard of people microdosing MDMA. I think the whole microdosing idea is a completely different model. I'm not critical of investigating that, but to me, you know, that's talking about the ongoing, at least several times a week, effect on the organism. Our idea is the drug is only a catalyst for the experience. This is our hypothesis, which I think is borne out by the durability of the results. So, the way I see it is MDMA is just a catalyst, just like psilocybin would be or just like holotropic breathwork would be or just like prolonged meditation, perhaps, or other methods of shifting consciousness, and that opens the possibility of this new experience. 

The snow analogy was actually Mendel Kaelen’s originally. He’s a researcher in London. Michael Pollan, I guess, quoted it. Anyways, some of the neuroscience research is about that, the way the network relationships change, and so it's sort of like new fallen snow. Suddenly, you can get out of that rut. You can have a new and unexpected experience. But I think there's a real danger in thinking after that, you need to keep having more medicine. That's a big experience that may take years to integrate, certainly weeks or months, and so, I think the idea of frequent use doesn't appeal to me. I think it's kind of counter to the way I think about this approach to healing, because it's not coming from the medicine. It's coming from the person's own inner capacity to heal once the obstacles are removed, and they have some catalysts to help them connect with their own innate capacity to heal. That's how I see it. 

Now, would it be useful to have another session in six months or a year or periodic sessions over time? We don't know the answer to that, but I think that is consistent with the

model, the way I think of it. That doesn't mean it would never be helpful to kind of have another chance to clear away the cobwebs and check in with yourself. In our long-term follow-up, most people said they didn't need any more sessions then, but most of them thought, well, maybe a session in six months or a year to help me kind of reconnect with the realizations and the shifts. So, I think that'll be a good thing to look at. We've got data. Actually, our longest follow-up was an average of three and a half years. Minimum was seventeen months, but maximum of five years. It was a separate study after our first MDMA PTSD study. What we saw was the average CAP score of PTSD symptoms was numerically slightly lower, but statistically the same at three and a half years as it was at two months on average. 

A few people had relapse, but those were included in that data. So, for the other people, if anything, the improvement in PTSD tended to increase over time. Like in our phase two twelve-month follow-up, a little over half the people no longer met criteria for PTSD at two months. At one year, it was two-thirds of the people. So, that's consistent with this idea that it's not about more medicine. It's about the process continuing to unfold. 

Shiv: That's fantastic data. Thanks for sharing that. That's really important for our audience to learn about and know. I want to be respectful of your time, so I only have two last questions for you. The first is just what advice do you want to give to our audience about how you've approached your career that maybe they can learn from? 

Dr. Mithoefer: Well, I would say don't be afraid to change if something is not as compelling as it once was and something else seems more compelling. 

Shiv: Yeah, I love that. 

Dr. Mithoefer: There's room for more than one career, I think. Well, you know that. Yeah. 

Shiv: One of my favorite guests we've had in the podcast is Lisa Sanders, who's an internist at Yale. She started med school as a thirty-seven-year-old after a career as a journalist. She took that and made a really successful career in medical journalism as the regular author of the New York Times Diagnosis column, which was turned into a Netflix docuseries called Diagnosis. So, I love that. Again, your story is fascinating and a good one. I'm glad you didn't have that ego to not go back to psychiatry residency because clearly you've had a great impact on many people since then, directly and also indirectly with the work you've done with research. 

Is there anything else that you want our audience to know about you, about MAPS, psychedelic assisted therapy, or anything else? 

Dr. Mithoefer: I would say as we get justifiably enthusiastic about our reductions in PTSD symptoms, let's really pay attention to the bigger picture of what people are reporting and what these experiences are really like, because I don't want to be reductionist about what's going on. We're far from understanding what's really happening here in the broader picture. So, I want us to remain curious and realize there's an opportunity to learn some really exciting and basic lessons about the nature of human healing that's a quite different from the DSM disease-focused model. Not that that has no meaning, but it's not the main thing. 

I'll end with a quote from Stan Groff. He said, “Used intelligently, psychedelics could be for psychiatry and psychology what a microscope is for biology and a telescope is for astronomy.” So, we're on the brink of exciting explorations. It's much more than just decreasing DSM symptoms. 

Shiv: I couldn't agree more. Dr. David Yaden is a mentor of mine as well, Bit’s husband, and his whole remit at Hopkins is human flourishing, and that's definitely an area of interest and one reason I've gone back to Hopkins to study with him. So, Dr. Mithoefer, I'm really glad we were able to have this conversation. I appreciate your time today, and more importantly, again, the work that you've done over decades to help patients directly and then also scale out this work at MAPS, which is truly very exciting. 

Dr. Mithoefer: Well, thanks a lot Shiv. It's really fun to talk to you. I love talking to people that are actually really well-informed about this. 

Shiv: Thank you. I try my best and I've benefited a lot from talking to people like you and Rick and others who I'm very grateful for. So, with that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show, and remember to do your part to raise the line and strengthen our healthcare system. We're all in this together. Take care.