 The following is a conversation with Rick Doblin, founder and executive director of the Multidisciplinary Association for Psychedelic Studies, MAPS. He is one of the seminal figures in both the cultural history and the cutting edge science of psychedelics. He was there along with the biggest characters throughout this fascinating history of psychedelics, and he is here to tell the story. Quick mention of our sponsors, Theragun, ExpressVPN, Blinkist, and Asleep. Check them out in the description to support this podcast. As a side note, let me say that exploring the places the human mind can go can help us understand where it comes from, how it works, and how to engineer mental journeys, whether that's through life experiences, chemical substances, brain computer interfaces, or interactions with artificial intelligence systems. On a personal level, I think the dissolution of the ego for stretches of time is a powerful tool for understanding yourself. A lot of things can do this, including jiu jitsu, literature, meditation, but psychedelics is definitely, or at least arguably, one of the most powerful, from psilocybin to DMT. I'm excited that people like Rick are leading the scientific research that reveals the efficacy and the safety of these substances so that their proper dosage and usage protocols can be understood and people like me can safely and effectively use them, not just for recreation, but for rigorous exploration of my own mind. This is the Lex Friedman Podcast, and here is my conversation with Rick Doblin. Could you give an introduction to psychedelics, like a big, bold, whirlwind overview? What are psychedelics? What are the kinds of psychedelics out there? In whatever way you think is meaningful. All right, well, when I started MAPS, the Multidisciplinary Association for Psychedelic Studies, it was very important for me that psychedelic be in the name. And the way in which the original meaning of psychedelic, it's mind manifesting. It was created by Humphrey Osmond in a dialogue with Aldous Huxley. And so psychedelic means mind manifesting. And so we interpret that very broadly to mean dreams are psychedelic. Anything that kind of brings things to the surface, holotropic breath work, hyperventilation is psychedelic. So most people think psychedelic is only about certain kind of chemical substances, either natural or synthetic, but we've got a much broader view of that. Meditation can be psychedelic in some ways, but our primary focus is on the drugs, is on the medicines or the, you might call them, some people might call them spiritual tools or sacraments. There's sort of two general categories of those. One are what are called the classic psychedelics, and those are the ego dissolving, sort of merged into unitive states. Those are like LSD, psilocybin, mescaline, ayahuasca, ibogaine, DMT, things like that. And then there is MDMA, which some people even argue is not a psychedelic. They'll say it's an empathogen or an intactogen, it's about touching within or empathy. It doesn't do the same kind of ego dissolution that the classic psychedelics do, but it brings material to the surface and it changes the way we process information. And so I think you can quibble about whether it's, it's certainly not a classic psychedelic, but I think MDMA is also a psychedelic. Marijuana, I would say, is a psychedelic. Marijuana is closer to the classic psychedelics than it is to MDMA. One point I like to make is dreams, because then everybody can relate to that. Dreams are psychedelic. Dreams bring emotions, feelings, ideas, concepts, in symbolic form a lot of times, or just in raw emotions to the surface. So when people hear the word psychedelic, often they are frightened by it. It's about loss of control. And it is, to an extent, loss of conscious control, particularly with the classic psychedelics. And we know with dreams that we can have frightening dreams, nightmares, but I think that anchoring the concept of psychedelic in dreams is really helpful for people to know that it's kind of a natural state and that there are other ways that you can catalyze it than by going to sleep, and that for thousands of years, substances have been used in that way. So you mentioned this idea of bringing something to the surface, which is really interesting. So can you maybe elaborate the surface and what is there in the depths of things and how does ego dissolution fits into that? Well, Aldous Huxley talked about the brain as a reducing valve, that we have an enormous amount of information. So right now there's an air conditioning sound in the background, but that's not crucial to what you and I are doing, talking to each other, so we kind of tune that out. There's all sorts of sights and sounds. There's incoming information in all the different sense modalities, and we have to figure out what's important to us. And so the mind, in a way, focuses a lot on what are our core needs? And we filter all the incoming information that we get towards focusing on what our core needs, and we can even get to Abraham Maslow and the hierarchy of needs about survival needs, belonging needs, esteem needs, go on. So I think what I mean by bringing things to the surface is that we tend to not focus on a lot of things that are coming, but we also push away things that are difficult emotionally, difficult cognitively. We all know that we're on this very short trajectory from birth to death, but we're not constantly thinking about dying, although that can actually be helpful to focus us on what's really important. Traumas are often suppressed. Conflicts, we see in America and around the world a kind of rise of irrationality where people push away their logic in order for their emotional tribal needs to be met. A lot of people are suffering from early childhood traumas of a different kinds or abandonment issues or anything. So we tend to focus on just what we need to survive and what we need for work and esteem. And so psychedelics, by dissolving this ego control or by with MDMA kind of strengthening our sense of self and our sense of self acceptance, we can bring in other information that have previously been too complicated or too painful. You don't think of psychedelics as conjuring up something new. It is more revealing something that is already there. I think that's a very crucial thing. So yes, Sasha Shulgin who sort of the godfather of MDMA, he sort of rediscovered it and brought it back into use. He talked about his first experience was with mescaline. His first psychedelic experience was with mescaline and he had a tremendous experience. But what he said about it was he was having a human experience that the mescaline was helping him access rather than that he was having a mescaline experience. So that it's not like you pop a pill and you always have the same kind of experience as everybody else. The experience is not contained in the pill. The pill opens you up and you have an experience of yourself. Sometimes these are experiences that we've never consciously had. But we can say right now that we know that our body below the level of our conscious awareness has all these self healing mechanisms. And we don't modulate them to a large extent by conscious control. I mean, eventually we are learning more about the mind body and we learn about the placebo effect, how what we think is the case. But I think that there's experiences that are below our level of conscious awareness, particularly once we're adults that are more of these unit of mystical experiences, sense of connection. I think kids are like this a lot. We kind of come from the void, you could say, and you're born and you have a different way of processing information. One interesting point about that has to do with ketamine, which is been approved as ketamine for depression, but it's used for anesthesia. And roughly one 10th the anesthetic dose is a psychedelic dose. And when it's used in anesthesia, there's what's called the emergent phenomena. So this is, you get enough ketamine for, you can be operated on, you're not in pain, you're not really there, your ego's knocked out, but you can still breathe. But as the operations get over and then people metabolize the ketamine, there's a process that they call the emergent phenomena. It's like as you're emerging from this tranquilized state, and that's where you pass through the psychedelic phase. And they don't prepare people for that. And what we see is that a lot of adults have difficult times with that, but children don't seem to have those problems. Children are a little bit more already in this kind of state. And so ketamine is used quite frequently in children now for anesthesia. So all of that is to say to your question that I think the psychedelics reveal things that are within us. Some things that are how we process information back when we were children. Other things that we've never thought of before that are sort of baked into our consciousness. There's one drug, 5MeO DMT. It's this toxin from a Sonoran toad that many people consider it to be the most powerful of all the psychedelics. And it kind of knocks the ego structures completely out of it and we experience something different, but it's something I think that's always within us. It's at a deeper layer. So we knock out some of the higher cognitive functions and then we experience things in a different way. So my sense is that these are human experiences that the psychedelics bring us to. Yeah, it's really profound. And DMT is a really interesting example. So Terence McKenna has talked about these machine elves. And there's this, I think from the people I've heard speak about the experience, there's a sense that you are traveling elsewhere to meet entities, whether they're elves or not. So in your sense, you're not traveling elsewhere. You're just revealing something that's within and maybe it's a particular mechanism of revealing what's already within. Yeah, and I knew Terence. I spent a lot of time talking with Terence and I do not ascribe to a lot of things that he was saying. He was a tremendous entertainer and I think he did a lot of really good things and focused us on the power of psychedelics. But I think I've never seen these quote machine elves. I think culture is more determinative of what people experience under psychedelics, your preconceptions, than we give it credit for. And so I think there's a lot of priming that you could say that people receive by stories from their culture. With ayahuasca, it's about jaguars and Amazonian animals. And so I think these machine elves are this construct of Terence that other people do see. There's actually some people that are very interested in doing a study and that they're well funded and moving toward it to keep people on an IV infusion of DMT for them specifically to see, do they contact machine elves or aliens and what kind of information do they bring back from these other selves, other places or other entities? One question is, who are we? Are we connected to everything in the universe? We certainly know in many cases, you talk about waves or particles, the quantum approach. So I don't interpret experiences that we have of some entity that's somehow or other deep in our consciousness that's not us. It's a part of who we are. So I tend to interpret it in that way. The question is, how big are we? And how many ideas are within us that can be revealed by changing the perspective? You mentioned physics. What physicists, especially mathematical physicists or mathematicians do is they reveal truths by taking a slightly different perspective on a problem that reveals the simplicity of how it actually works in totally new ways. That's what Einstein did. Like every progress in physics and certainly every progress in mathematics requires you to take a different perspective. And then perhaps that's exactly what psychedelics are doing. It's not that they're contacting aliens that are elsewhere. It may be revealing the connection between us and other living life forms, or actually it might be revealing a totally new perspective on what life is or what consciousness is and giving us a glimpse at that even though our cognitive capabilities are limited to fully grasp and understand it. So it's just giving us an inkling of that somehow. And it seems perhaps a little ridiculous not from a scientific perspective in the sense that we don't have a good physics of life or physics of intelligence or physics of consciousness, but getting a glimpse of that is giving us a little bit of maybe an intuition of which way to head to build such a physics. Yeah, yeah, I think so. I think that there's this other concept I guess I would like to talk about briefly, this Jungian collective unconscious, this idea that somehow or other everything that has ever happened is still accessible, maybe not with as much data or as much resolution, but that there's wave resonances. So that I do believe that we can have experiences as part of this human collective unconscious that we're not from our own life. Yeah. And that we can, it's like the holographic realities and that there is a way to gather information that can be accurate about other times and places through depth investigations of our own consciousness. But I think what I tend to believe is that it's because there's emotional resonances between where we're at now in this life and other kind of experiences that people have had before. And we always hear about everybody who talks about past lives, they're always kings and queens. So I think that's again, you filter things what you want to be true. But I do think that there is a way to access information beyond what we've taken in in our own temporal existence through our own five senses. In some ways, I really find that compelling, the notion that that information is already there and you're simply just moving the attention of your mind to different parts of that. Yeah, I mean, we have that with the radio. I mean, you got a frequency, you turn all this information, you could actually say right now in the space between us, we have the whole world's knowledge that's up on the internet. It's right here. But we don't see it. We just have to tune in. Yeah. What are the interesting differences, would you say, between the various psychedelics that you mentioned, ayahuasca, DMT, acid, LSD, marijuana, mescaline, PCP, psilocybin, MDMA? You mentioned a few of them that are really interesting. We'll talk about scientifically some of the different studies that have been conducted on each, but sort of at the high level. What are some interesting differences? Well, one of the big ones that people make a big deal of that I think is completely misplaced is some are from nature, some are from the lab. So there's this kind of like romantic thought that if it's from nature, it's good. If it's from the lab, it's somehow tainted by humanity. And therefore, some people are like all for plant psychedelics. We see the policy changes that have been happening in a couple of cities, Cambridge, Somerville, not far from where we're at now, where they decriminalize plant medicines. So they call it decriminalizing nature. So I think that there is, from my perspective, certain things from nature are poison, certain things from the lab are spiritual, even if they don't show up in nature, like LSD. Now there is something, LSD is lysergic acid diethylamide. There is lysergic acid amide, LSA, which comes from morning glory seeds. So it's very similar. But at the same time, I'd say, I don't buy into that distinction that there's some fundamental preference. One of the things that Terence McKenna, since we talked about him, he talked about how if it's from nature, it's good. And if it's not, we should be suspect. Of course, he had a lot of great LSD experiences. But actually Terence, in 1984, we were at Esalen with a bunch of other people. This was before the crackdown on MDMA. And this was some of the underground therapists and the above ground researchers who were trying to talk about how to protect MDMA from this eventual crackdown. And Terence was like, forget about it. It's from the lab. It's dangerous. We have thousands of years of history, all these other things. And what do we know about MDMA and blah, blah, blah. I was like, Terence, you're so unscientific. Another way to say it is, and I just said, we need a study of the safety of MDMA. And so then Dick Price, who started Esalen, I said, I'll put a thousand, Dick Price, he put a thousand. So Terence was actually the catalyst for the first study with MDMA. Just because he was so frustrating about how plants are okay. And if it's from the lab, it's bad. So that's one distinction. The other distinction is that he was a scientist. The other distinction is this sense of classic psychedelics versus things like MDMA. So to what extent do they dissolve the ego? And you could say, to what extent do they cause visions? The 5HT2A serotonin receptor subtype, which is responsible for a lot of that where these drugs are activating. Now, mescaline of all the psychedelics, chemically, it's the most similar to MDMA. It's a phenethylamine, which is MDMA. So in the 50s, there was the, 53, I think it was, the Army Chemical Warfare Service wanted to look at drugs for interrogations, mind control, nonlethal incapacitants. They did a study in eight substances. These were now toxicity studies in animals. And on the one side was methamphetamine, and the other was mescaline, and MDMA was in the middle, chemically. So mescaline of these psychedelics tends to have the warmth that MDMA has. It's not as ego dissolving quite as some of the others. I mean, it's the main active ingredient in peyote. It is very psychedelic, very visual. Another distinction with these different drugs is how long they last. And a lot of that has to do with the route of administration. So for example, if you smoke DMT, it takes 10, 15 minutes, and you're, within seconds, you're off in another world. Similarly, 5MeO DMT, very rapid. When you take DMT in the form of ayahuasca, where it's mixed with another substance that makes it so that it's orally active, then it's a couple hours. So LSD is eight, 10, 12 hours sometimes. Psilocybin is more like five or six hours, or four to six hours. MDMA is similar. It's one reason why in our research, we give an initial dose of MDMA, and then two hours later, we give half the initial amount to extend the plateau, because we want it to last longer for people to be in this therapeutic state. So that's another distinction is how long these drugs last. Another distinction is which of them come from a religious context, have a religion built around them. We have this sense that some people are saying that 5MeO DMT and the Sonoran Toad, that they have this long history of indigenous use, but they don't, that's all modern, it's made up, and it's kind of a new approach. However, there was thousands of years of use of psilocybin mushrooms in religious contexts. From 1600 BC to 396 AD, the world's longest mystery ceremonies, the Eleusinian Mysteries, sort of the heart of Greek culture, the heart of Western culture, that was a psychedelic potion called Kikion that seems like it's very much like an LSD like substance. Aragat on grain and LSD comes from Aragat. So I think that there are a lot of ways to look at these different substances. Another distinction is which one of them are being researched right now in scientific context and which are not. And because of the rise of all these for profit companies and everybody's looking for what they can patent, what they can claim, the land grab, more and more there are companies looking at every different kind of psychedelics. The ones that are most important that are not being researched, Mescaline, but now there's a company to do Mescaline, the Jernico Lab, Ibogaine, which is crucial for opiate addiction. There's a new company, a branch of this company, Atai, that's gonna be looking at Ibogaine. So I'd say the rise of the for profit companies is making it so that there's just gonna be an enormous amount of investigations into all these different psychedelics. But what we're gonna see is the development of new psychedelics that we don't know anything about that have not existed yet because a lot of these for profit companies are gonna wanna invent and patent and have composition of matter patents on new molecules. So I think we'll see a lot of that happening too. That's really fascinating. I mean, there's a lot of doors you've opened and we're gonna walk through all of them, including the research and so on, but on this one little tangent of the future of psychedelics, so engineering new psychedelics, can you comment on maybe the chemistry and the biology of how psychedelics work and where is the space of possible engineering of psychedelics and what kind of things might they unlock in terms of the possible places our mind would be able to go and the effects of that of improving health, but maybe at the basic level of chemistry and the space of what could be engineered? Well, you reminded me, I'll get to exactly what you said, but you reminded me of a talk I heard by Buckminster Fuller shortly before he died. And what he talked about is how technology was making things ever smaller, that we are able to pack more and more information into smaller and smaller spaces and that we're developing technologies of communications with people, we now know the internet and things like that. But what he said is that he thought the eventual evolution of this sort of research would move from this miniaturization to telepathy. Yeah. And that was like a shocking thing for somebody like scientific like that to say that. So will we unlock those parts where I talked about the collective unconscious? Will we be able to more consciously explore those areas? So I think that that's a possibility. There was Stan Groff, who's the world's leading LSD researcher and has been my mentor, his wife Brigida. They were talking about stories that they had heard about MDMA that people take and then on top of that, they do 5MEO DMT. And so you get this ego dissolution, but underneath it, you have this sense of ego, sort of sense of self safety, of self acceptance, kind of grounds it. So Stan was like, that's the future of psychiatry, that you can watch without the terror of the ego dissolution, the sense that you're losing your mind or you're going crazy or you're dying, or that you have this grounded sense of safety while you're dissolving your normal sense of how you see things. And being able to engineer in a fine tuned way that exact experience, maybe fine tuned to the person, as opposed to sort of this manual potion that's through experiment. Although I don't know about fine tuning things to the person in the sense that we believe there's this inner healer, this kind of inner healing intelligence. We talked about it, the body repairs itself. So I think we more need to create safety for people and then what emerges will be customized to what they need to be looking at from this inner healing intelligence. At the same time, we will move to, we hear so much about the new approaches to oncology where you do genetic analysis of different kinds of tumors and then you have certain kind of chemotherapy agents and you do like personalized chemotherapy. I think we will have more like personalized psychedelic therapy, but it'll be more like a sequence of different drugs that people go through over an extended period of time and then you kind of customize what's next and sometimes you'll combine different drugs together like this 5MeO DMT and MDMA or a lot of times people do LSD MDMA combinations or psilocybin MDMA combinations. Chemistry is not my strength. I'm more into clinical applications and policy, but I can say that from what I've learned from reading from others and research done by others that different psychedelics have an impact on different neurotransmitters, different other parts of energies in the brain. The default mode network is what's considered to be like our sense of self and it's part of the brain that sort of is what I described before, scanning the world and filtering information for what's really important to us and both focusing us on things and also helping us to ignore a lot of things. And the classic psychedelics all weaken the energy in this default mode system and therefore you get this flood of information that you're not normally paying attention to and then you start seeing in the more creative waves or more connected, you actually move to beyond the verbal kind of thinking into sort of symbolic thinking a lot of times and that's where you sometimes get these mystical sense of connection, how it's all one and you get the sense also of how big the universe is and how small each one of us is. So there's a lot of work that Sasha Shulgin and Albert Hoffman who invented LSD and first synthesized psilocybin on what they call structure activity relationships. What is the structural molecule and then how do you predict what that new molecule that never existed before is going to do once you actually take it? And you can get close, but you never really know until you actually take the drug. And the way that Sasha ran his experiments is that he would take the drugs himself first in low doses and he would sort of step up the doses to have more experiences. If he thought it was valuable, he'd share it with his wife, Ann, but then what they would do is if they both thought it was valuable, they had a group of 12 people that they were with for many, many years and they would distribute these new drug to these 12 people and they would get the different perspectives. And he felt that 12 was like a minimum number because we're so unique how each of us see things, but then you kind of get a little bit of a consensus on how a lot of people are gonna see it and then if that 12 people were positive about it, then they would turn it over to Leo Zeph, who we called the secret chief, the leader of the underground psychedelic therapy movement and then he would start exploring it in therapy. So there's still a lot of mysteries as far as structure activity relationships and it's not gonna be the case that people go into the lab and they tinker with molecules and they know exactly what they're gonna get. And a lot of it has to do with not so much chemistry as morphology. You could say the shape of the molecule and how does that interact with receptor sites. And so we're getting better at modeling all of that. And how does that interaction relate to the morphing of the human experience and deeply understanding that perhaps there's no equations yet for that kind of thing. You really have to build up intuition by experiencing it. And over time and sort of subjective self report, like trying to build an understanding of the effects of the different chemistries. Yeah, you can have approximate ideas, but to know exactly. So when I first tried MDMA, which was 1982 and this was after I had done lots of LSD and mescaline and mushrooms, I was shocked at how different it was than these other substances and yet how profound it was. So are there whole new kind of categories of classes of drugs that we're not aware of that would be not so much this like eco dissolution or emotional? Well, what MDMA does is reduces activity in the amygdala, the fear processing part of the brain. So it's not just chemistry, but it routes energy throughout the brain in a different way. It increases activity in the prefrontal cortex. So you think more logically, that I think has an enormous impact on the effect of MDMA. The other thing it does is it increases connectivity between the amygdala and the hippocampus. So it helps facilitate processing of things into longterm memory. And with PTSD, trauma is like never in the past, it's always about to happen. So will we one time develop drugs that would even be specific to certain kinds of memories? We're working with a woman, Rachel Yehuda, who is at the Bronx VA, and she's done some studies that are with the epigenetics of trauma. So she's worked with Holocaust survivors and their children, and she has identified epigenetic mechanisms by which trauma is passed from generation to the generations. Sort of like set points for anxiety, fear, certain things like that. But the question is, can you actually transmit memories from one generation to the next? Now, this is not DNA changes which happen over a very long period of time and evolutionary scale. But within one lifetime, within some experiences, your epigenetics, what turns on the genes or turns off certain genes, that can be impacted. And that's what we know now can be transmitted from generation to generation, either by the father or the mother through the sperm or the egg. So it's pretty remarkable. So what Rachel's gonna try to do is MDMA research for PTSD and look at these epigenetic markers before and after and see if they change as a consequence of therapy. So will we develop one day certain kind of chemicals that will be able to bring certain kind of memories to the surface? That's not inconceivable. The epigenetic angle is fascinating, that there'll be these epigenetic perturbations that lead to memories living from one generation to the other and then bringing those memories to the surface and using that as signal to understand what exactly the psychedelics bring to the surface and not. Yeah, yeah. Now, the other portion of that though is culture. I mean, culture is where we store all these memories and in the stories that we get passed out. Especially with a lot of shared, you talk about the Holocaust or World War II, where it's deeply ingrained in the culture, the impact of those events and sort of in aggregate the different perspectives on that particular event create a set of stories that you can plug into. And then they kind of resonate with some aspect of you that creates a memory that's connected to, like when I think about World War II and the Holocaust, I think about my own family, but in some sense, it's also resonating with stories of many others. So it's like somehow the two echo each other and I'm just providing my own little flavor on top. The meat of the stories are probably those that are shared with others. It's plugging into the collective unconscious. That's really fascinating, really plugging into like precisely plugging into particular memories as a way to deal with trauma and PTSD, that kind of thing. Yeah, I'll just add that the most important dream of my life ever was of a Holocaust survivor telling me that he was miraculously saved from death and he knew that he was saved for a particular purpose, but he never knew what that purpose was. So in the dream, I'm seeing him on his deathbed and then he shows me whatever happened to him during the Holocaust. And then we're back in the room on his deathbed and he says, well, I know what my purpose was now. And I'm like, oh, great, what was it? He says, it's to tell you to be a psychedelic therapist and to study psychedelics and bring back psychedelic research. And I thought to myself, I've already decided to do this. You can lay this on me. I can say yes and then you can die in peace. And then he died in front of my eyes in the dream. So I think that that kind of cultural transmission that I got from when I was really young, then manifested in this dream. And that was this story about how people can be incredibly vicious and can be very motivated by irrational factors. And so I just feel that this kind of multi generational transmission of this story of the irrational being a murderous factor and something I needed to respond to was deeply ingrained. And I would say my guess is more culturally than this epigenetic mechanism. Yes. Yeah, but your sense is that whatever stimulated a certain part of human nature in World War II, especially Nazi Germany, but also in Stalinist Soviet Union, still is within us, within all of us. Just like what we're saying, we embody quite a lot of things. Yeah. And one of those is whatever the capacity for evil seems to be one of those things. Yeah, there's a quote from Carl Jung from just a few years before he died. What he says, and I'll just paraphrase it is that we need to understand psychology. We need to understand who man is, that the greatest danger to us is man. There are no other dangers really that impact our species. And then he goes on to say that we are the source of all coming evil. Now this was 15 years or so after World War II. But yeah, and I'd say one of the most important psychedelic experiences of my life was a DMT experience. Also Terrence was there, Ralph Metzner, Andy Weil, a few others. And we were sitting around at Esalen smoking DMT. And under the influence of DMT, which now this was the first time I've ever smoked DMT, I had this super rapid fraction of a second, like dissolving of everything that I, well, first off I saw a horizontal line, then I saw a vertical line, then it turned into a color, red, then it was red, then it turned into cubes, then it turned into like an MC Escher kind of like, I don't know, you know, didn't make logical sense. And then I was gone. And then it was just this period of five, 10 minutes of just feeling part of this enormous wave of billions of years of evolution, how I had this sense that in my innermost sense of who I am uniquely individually, this inner voice that's talking to me that I didn't develop English, that it's like a gift to me from millions of people. So that even in my most innermost sense, it's not just me. It's the product of everything that came before me. I'm part of this bigger system. And then I just thought, wow, just how many billions of years does it take to reach this point of self awareness and all this? And it was glorious, beautiful. And then I had this thought, and this is where this kind of intellectual honesty, I guess you could say, I just thought, well, if I'm part of everything and everything's part of me, then it's not just the good parts, that Hitler's part of me too. And that was just this shock, like a stone sunk, and I just was very moody for the whole next day. But it was that acknowledgement that each of us carries these potentials, and what we activate is what matters, but what our potential are is the whole full range of things. I don't know if you can comment about the DMT trip itself and what it's like, starting from the very basic geometric shapes and then launching yourself into the context of the enormity of space and time in the human history. Is there anything else to be said about that kind of visually or physically or emotionally about that journey? What it's like, that brief journey that reveals so much? Well, I was with a group of people. The way we were doing it was each of us would smoke DMT, have 10, 15 minutes experience while we closed our eyes, and everybody else was just chatting, and then the person who did the DMT would come back and tell their story of what happened. And then we'd think about it for a bit and then pass the pipe to the next person. And so this was like a whole evening. So even the, sorry to interrupt, even the conversations themselves then is part of the experience. Exactly, yes, yes, because it's also what you bring back. I mean, I think that's particularly for therapy. It's not so much about what the experience is, but it's what you bring back and what do you integrate. And then also, how do you learn how to do these things on your own without the drugs? There is this way, because we're saying it's sort of a core human experience, the drug is the mediator, but can we do this on our own? And once you've seen it and felt it, then you have a little bit better sense to recreate it on your own. Although, I've had dreams where I've been doing LSD and tripping and it was just incredible. It was, I was tripping in my dreams, but I had not taken LSD. So there's this way in which we do that. So I would say that from the DMT experience, the sense of safety, that's what I was trying to get at with this, the group of us and this group of friends trying to do this common exploration, that if you have this sense of safety, you're incredibly vulnerable because you are giving up your awareness really of what's happening around you. I think there's, what we're finding is that in our psychedelic research for PTSD and what we see with the vaccines, that even African Americans are reluctant to volunteer for vaccines because they haven't had that sense of safety from the medical establishment. They don't volunteer for psychedelic therapy even as much. So the overlay has to be this sense of safety as you become vulnerable and looking inside, you're not. I was just actually told about how there's a lot of work being done inside prisons to teach mindfulness. And so one of the, Charlene who's my assistant is trying to do work on helping people in prison with trauma, potentially one day with MDMA or meditation or mindfulness. But one of the exercises was teaching people to, okay, here's how you deal with stress, just close your eyes and deep breathe. And what Charlene was saying is people don't close their eyes in prison, you don't feel safe to do that. So all that is just to say is that the context is the most important factor. So while I'll talk about the DMT experience, the context was this supportive sense of safety that I could be completely vulnerable and out of any kind of controlled women, I think often are less safe in this way than men because of all the sexual assaults. But what it can do by taking the ego orientation offline to some extent, it opens you up to much more. And to make a bigger point of that, we could say that it's very similar to the Copernican revolution. And people thought that the earth was the center of the universe and the inquisition murdered people that questioned that. Father Bruno burned at the stake. Actually, one of the things he said, I think that's worth all these years later saying is that when the inquisition sentenced him to burn at the stake for espousing this idea that the earth was not really the center of the universe, he said to the inquisition, he said, your fear in sentencing me is greater than my fear in being sentenced. That their worldview was so rigid that they had to wipe out anybody that would question it. And so this idea of psychedelics displacing our ego is the center of the universe. And to realize that we are just rotating about on something much bigger than our individual life. Our ego is designed almost to protect this body while we're alive. And you can understand all the good reasons why that is, but it also disconnects us from this bigger reality. And so the psychedelics, DMT, by knocking this sort of ego orientation or the default mode network offline, you open up to the bigger sweeps of history. So in that place of safety and vulnerability in that fascinating group of people, when their ego was dissolved in this way, did they have similar experiences? Is there different places that their minds went? Yeah, so once I had this kind of shattering experience that Hitler's part of me, no one else in the group had that. Probably a lot of them have maybe had that before or they realized that they're not just the good, the white hat, good people and that they're all good and we got to fight against the bad people. So no, people will go in different places. And not only that, if you do it again, you'll go into a different place than you went to the first time. Unless you have not resolved the issue. So I had a sequence of LSD trips that were very difficult, but it was like coming to the same sort of conundrum, the same challenge that I was unable to overcome. This idea of letting go and really fully dissolving, letting the ego fully go. And I would have this sequence of trips over a couple of months where I would reach this point where I was too scared to move forward and I would just be holding on. So there are repeated themes sometimes. What Stan Groff has said, which I find very beautiful, is that the full expression of an emotion is the funeral pyre of that emotion. And what that means is if you can fully let in something, then the essence of life has changed, is that it moves on, that everything's in motion. And if you can fully experience it, even if it's a sense that you're gonna be trapped in eternity in this hellish state, if you surrender to that, that's the way out. This full experience of something is this funeral pyre of that emotion. And so that runs against a lot of what modern psychiatry is doing too, which is to suppress symptoms. Instead of supporting people to kind of explore these insecurities so that then they can contain them and then they can move on. So yeah, resistance is not a way to make progress. Right, right. Although one of the reasons why we do the supplemental dose during the MDMA or why there's advantages in a 10 hour LSD experience is that you have a lot of opportunities to come up against this resistance that may be too difficult to deal with and then you kind of push it aside and then a couple hours later you come back to it or you come back to it. Press snooze every once in a while if you're not ready. It's hard to do that. I think with MDMA, you can negotiate. That's, I think, a part of its safety in a sense. You can have this like, oh, I should be talking about this or I'm feeling this, but it's too much for me now. You can push it away. But with the classic psychedelics, this kind of membrane between the conscious and the unconscious, that once you take the drug and it weakens this membrane and things are coming up, it's very difficult to negotiate with it. The key to successful classic psychedelic trips is surrender. You've talked about that you first began to reconsider the negative health myths around psychedelics when you learned that the book One Flew Over the Cuckoo's Nest was written by Ken Kesey when he was in part under the influence of LSD. So how do you think LSD helped him, Ken Kesey, in writing that incredible book? Yeah, there's a process that's called semantic priming. And so what that means is that I say night, you say day. There's kind of normal patterns of kind of, you say one word, what kind of words come to you next? And so they've done some research. They, meaning scientists, have done some research where you give people a psychedelic and then you do this semantic priming. And what you find is they have a wider range of associations than they normally would when they're not under psychedelics. So I think for Ken Kesey, he was able with psychedelics to get a deeper kind of emotional connection to some of these states of mind that people were in this mental institution and that he could explore them more in depth and more eloquently. And also one of the things he talked about was the fog machine, was how people's minds were sort of clouded by the people that ran the institution and the fog machine would be coming in. So I think the imagery and the metaphors that he used a lot in the book could come to him during LSD experiences. And then now he wasn't doing very, when you're writing, you have to be literate. You have to be able to write. So it would be more like beginning and ends of LSD trips instead of at the peak. But I think you would get a lot of these, the feeling tones or the images, the metaphors, I think he would get these extent, also LSD lasts so long, you can get these extended focus and you can really elaborate on images. And so much of psychedelic experiences are poetic and metaphorical. I mean, you could take veterans who've never read a book of poetry in their lives. And under the influence of MDMA, just what they describe, the imagery and the way they describe their experiences, metaphorical, poetic, it's incredible. And so I think that Ken Kesey was able to channel what LSD did to his mind in a way that most people couldn't do, that he did because he was trying to write this novel and because he was so brilliant. Yeah, I mean, we'll talk about psychedelics and treating, in bringing some of trauma to the surface and dealing with all those kinds of things, but there's something also to the opening up of creativity for whether it's for writing purposes or for in my world for engineering, for invention, innovation and invention itself is a very, is a deeply creative process. And it's fascinating to think with the aid of psychedelics, what kind of ideas can be brought to life? Yeah, well, we have the whole phenomena of a lot of the people in Silicon Valley and else microdosing psychedelics in order to have a little touch more of this creative approach to things. I would love it to see if it was, that's more like Terrence McKenna territory, correct me if I'm wrong, but I would love to sort of more scientific to where there'll be the rigor of saying how to do it effectively, how to sort of understand sort of not just almost, to take the full journey of creative exploration and to do it for prolonged periods of time, for years, lifelong kind of part of your life of how it empowers creativity. I think, of course, you start with helping people deal with trauma, and then the next step is people who have moved past their trauma and are trying to do something, create something special in their life. How can then psychedelics empower that? Yeah, now, that also, just to not shy away from anything controversial, that gets us to this idea of psychedelics for vision quest, particularly for younger people. You know, when you're sort of moving into this adulting kind of phase and you have to figure out what are you gonna do with your life, there's so many options. A lot of people, of course, feel constrained that they have very few options, but I think this idea of psychedelics as a way to help you find your calling or find your vision or find your unique leverage point, I think we'll see that more and more as our culture evolves and gets healthier around the use of psychedelics. So it's both the science, having the rigor of understanding how to do it safely and the culture catching up to the fact that this is both safe and very useful. Yeah, although I would question this idea of safety. So we can understand physiological risks and we can minimize them. And I think there's very minimal physiological risks from the classic psychedelics, virtually none, or for even MDMA under safe conditions. Psychological risks are harder to address, but we can do that through the sense of safety and support. But I think there's a level of risk there that we shouldn't overlook. And so to make a drug into a medicine, what we have to do is prove to the satisfaction of the FDA and other regulatory agencies that things are safe and efficacious. But even though they use those words, proving safety and safe and efficacious, it's in relationship to the disease that you're trying to treat and you accept a certain amount of risk. So it's the risk benefit ratio rather than pure safety. Yeah, absolutely. Let me ask you about Ken Kesey a little bit longer because fascinating him being. He was also part of Project MKUltra. Yeah, yes. What was Project MKUltra and what lessons we should take away from it? Well, MKUltra was a program by the CIA. What they were looking at was, can you take these drugs, these psychedelic drugs, and weaponize them in different ways for interrogation, for true serums, for exposing somebody before they give a big talk to something like LSD and then they can't talk or make a fool of themselves? Or can you spray LSD over the battlefield and have everybody tripping and drop their weapons and then you just walk up and nobody dies and you've won the battle? So it's a fascinating concept. Yeah, they call it nonlethal incapacitance and I think that's how it's. One way to win a war is to enforce peace. To get everybody not caring about the war, but yes. Well, I think Gandhi said something even better, which is that the true way to win a war is to turn your enemy into your friend. Yes, that's a beautiful way to put it. Yeah, but MKUltra was really nefarious and it was part of our military and it was done in secret and they would dose people against their will. I mean, one of the most infamous things was that they had a house of prostitution in San Francisco and they would have one way mirrors, all this stuff and then they would just dose people with LSD and they would have the prostitutes dose these guys with LSD and observe what they would do and how they would act. And the CIA actually for a while was dosing each other secretly and that there's a famous case of this fellow Olson that either jumped out of a window or was pushed, he might've been killed. He was a CIA guy and they gave him LSD and then they're trying to see can they break him down and get him to tell secrets. And I think he felt uncomfortable with what happened to him while he was under the influence of LSD and whether he was pushed or not, I don't know if we'll ever know. But MKUltra was violating people's human rights. It was done in secret and the irony of it is that Ken Kesey is one of the people, one of the main early people that got LSD in this context and then he was one of the main people that helped inspire the hippies to use psychedelics to oppose the Vietnam War. So I think the CIA kind of in many cases, things get out of their control, what they think they can do and it turned in to be a disaster for them. I think there was some thought that some of the people at the CIA had is that if you can turn people inside, take drugs and they just focus on their internal experience, they're not gonna be involved politically. It's a way to sort of take people offline. And what I don't think they counted on is that when you're offline and you have these unit of special experiences and you realize how we're all connected, then why do you wanna go out and kill these Vietnamese and put one dictator over another dictator, dictators on both sides in North Vietnam and South Vietnam? Why are we doing that? So MKUltra has just a very disreputable. We're learning more and more about what they did and one of the unintended consequences was Ken Kesey and not only that, but then the Grateful Dead who began at the acid tests that Kesey was helping to organize and out of that emerged, you could say just this incredible psychedelic culture. And you look at the bands that began in the 60s and which ones have really survived to this day and the Grateful Dead has survived longer than most any other band. I mean, some of them have died and all, but it was like the tightness, the sort of telepathy we talked about before that they could just get so tuned in to each other and each other's energies and they could do improvisations and they can do this incredible work that I think the sustainability of the Grateful Dead as a group was a testament to the power of the LSD experiences and that might've never happened if not for MKUltra. But can we talk about the darkness a little bit? So Ted Kaczynski, the Unabomber was allegedly part of the MKUltra studies while at Harvard. Do you think this is true? Do you think it had an impact on him psychologically, intellectually and so on? I do think it's true and I do think it had an impact. So we talked before about are these drugs somehow or other producing a certain kind of drug experience or do they bring out what's within? So we have this experience, yeah, on the one hand, Ken Kesey and he sort of took positive things out of this. On the other hand, we can get this opposition to the modern world, to technology and to the point of creating bombs to try to go after it. So that the experience is not in the drug, it's this interaction between the drug, the person, the context. And so we can heal people with psychedelics or people can be driven crazy with psychedelics. It depends again on the context. And so I think both these things can be true. And I think it was really good that you kind of highlighted this, that there is this polarities and that it's not in the drug, it's in the other factors and it's who they were beforehand and then how you use that experience. So all that's to say is if we put LSD in the water and everybody were to get it, it doesn't mean that all of a sudden everybody's gonna have a mystical experience and then that's all we need to do and humanity is spiritualized or end war and all of this. It's not about the drug. And that actually is why for me, we've also talked about engineering new psychedelics and all the people that are gonna be trying for profit companies to develop and patent new psychedelics. For me, the most important challenge is new cultural contexts that can create legality, safety, support for the existing psychedelics that we already have. I mean, we have so much incredible tools in these existing psychedelics that it's more about creating context for them to be used in safe medical or personal growth or recreational even with harm reduction, all these different ways. That's more important to me than finding some new molecule that's somewhat similar or somewhat different but it can be patented. So it's the social context. So I do believe that Ted Kaczynski was part of NKUltra and I think it affected him in a negative way and that's a cautionary tale that it's not in the drug, it's in the context. The context, the person, still it feels like if viewed from a therapy perspective, perhaps there was a way to use psychedelics to help Ted Kaczynski find a path out of the darkness. I think so and I think that this is where I think MDMA comes in in a way that MDMA is, he felt very isolated and very much out of society in some ways. MDMA stimulates oxytocin, which we haven't mentioned, which is the hormone of nursing mothers, of love and connection. It provides a lot of this sense of self acceptance and safety and wanting to be in a relationship. There's Gould Dolan is a neuroscientist at Hopkins. She's given octopuses MDMA, they're solitary creatures except mating season, which is not very often but you give them MDMA and they become more interested in hanging out with other octopuses. So I think this, for people that have had difficult psychedelic experiences, MDMA helps them integrate them. We've worked with people that had a difficult LSD experience 40 years before and are still able to get back to that under the influence of MDMA and work out some of the conflicts that they weren't able to resolve all those decades before. So I think that psychedelics could have been helpful in a different context for Ted Kaczynski. But the other big part of it is that people have to be willing to cooperate with the experience. We talked about resistance. So people can resist these things. It's the saying is you can bring a horse to water but you can't make them drink. This is about how people have to be willing to go to these spaces. So one of the essence of our therapeutic approach is that we help people to heal themselves, that we are not giving them the healing. It's a flip on the power dynamics that existed, you would say in the fifties and sixties, my dad was a doctor and the doctors were gods and whatever they said was right. And we no longer, of course, believe that. But for a while, psychoanalysis with Freud, that they gave the interpretation to the patient. The patient couldn't help themselves but they would do the free associations and the psychoanalyst would see these conflicts and would be the one that does the healing, would give this interpretation and that would open things up. So I think it's this idea of empowering people to heal themselves. And so if Ted Kuznicki had been in a therapeutic setting with psychedelics and if they'd had something like MDMA available or MDA, which was popular during the sixties, which is a more like MDMA LSD combination, the outcomes might've been different. Let's take a step into the world of studies. Timothy Leary, who was he and what were the most important ideas you've learned from him? Well, I did have the opportunity to get to know him personally and to spend some time with him. Timothy Leary, well, let's start with Nixon saying he's the most dangerous man in America. That's a good place to start. Yeah. And why did Nixon say that? It's because of this turn on, tune in, drop out. Timothy Leary was just an incredible advocate for think for yourself, question authority. Those were the things he said all the time. Think for yourself, question authority. He was a rebel. He was kicked out of West Point. He was a psychologist who was at Harvard for three years from 60 to 63. Before he got to Harvard, he had an experience with mushrooms in Mexico. And he said he learned more in that experience than he'd had in his entire academic career before then about how the human mind works. And so he came to Harvard wanting to do research into psychedelics. And he did some very important studies, both of which, well, one was called the Good Friday Experiment, which was whether psychedelics in religiously inclined people taking psilocybin in a religious setting, whether it could produce a mystical experience. That took place at Marsh Chapel at the Boston University. Because it's a little bit subjective, where you can say entirely subjective, what people describe happens to them. He wanted to do another study, which would be a more objective measure, and that was called the Concord Prison Experiment. And that was the thought, if you can give people psilocybin mystical sense of connection type experiences while they're in prison, when they get out, they'll be more pro social and they'll have reduced recidivism. So Tim did that. He also did the naturalistic studies of giving loads of people psilocybin and sort of writing down what their experiences were, the range of experiences. Later on in his time at Harvard, they started doing LSD. And LSD is more cerebral, longer lasting, not as reassuring in a way as psilocybin. Sometimes he used to say that if they never got into LSD, they'd still be at Harvard with the psilocybin. So he was a great American psychologist, but then he got tired of the psychology game, you could say, or he would say that. He got more and more interested in cultural change and various musicians and artists and all sorts of people started coming to him for the psychedelic experience that they are in a way for creativity, for other things. So he started hanging out with all sorts of famous people or creative people and he stopped going to classes a lot. And Ram Dass, Richard Alpert had given LSD to a student that Ram Dass was courageous enough to admit that he had a sexual interest in. They weren't supposed to give it undergraduates. That was about the only time that they ever did it. And psychedelics just getting more and more controversial even in the early 60s, eventually got kicked out of Harvard and then he became kind of a cultural icon for the counterculture and was hounded by the police and Nixon and spent a lot of time in jail. I mean, he's an incredible person. One thing that Ram Dass said is that Richard Alpert, Ram Dass said, I'm a rascal, but Leary's a scoundrel. What's the distinction? Rascals like in good fun. A scoundrel is like, you can't quite trust them, I think. I think that. It's a spectrum of sorts. Yeah, I think that Leary was someone who a little bit got addicted to media attention. But I think that overall he gets blamed a lot for the backlash against the 60s, the shutdown of psychedelic research. I think that he is unfairly blamed for a lot of that. I think when you look back at the 60s, the common narrative is that it was because psychedelics going wrong. People took psychedelics, they weren't prepared, they had emotional breakdowns, they weren't psychotic, they killed themselves, they did this or that, different problems of people taking psychedelics in context that they didn't feel fairly safe in or just they weren't prepared or they didn't know how much they were taking or all this. So the backlash was because psychedelics going wrong. But I think the real reason, while that did happen, I think the real reason is psychedelics going right and people having this sense of connection. And then the opposite of what the CIA was hoping that it would kind of turn people inward and take them away from political struggles, it actually motivated people. Once you actually have these psychedelic experiences, your attitude towards death changes also this idea of death becoming an intrinsic part of life, it's a natural cycle, it's not so much. So I think people realize that, while there's this billions of years of evolution, infinity, whatever that means in terms of time, that we're here for a very limited time and they end up wanting to use their time well, they have a lessened fear of death and they wanna build this paradise on earth here now instead of later. So a lot of people really did get motivated to challenge the Vietnam War, to work on the environmental movement, civil rights movement, women's rights movement, anti militarism. And it was that challenge to the status quo that caused the backlash. So Leary is someone who in 1990, we had the maps I started in 86. So in 1990, we had this conference to raise money out in California and Leary was there and Ram Dass was there and Ralph Metzner was there and Andy Weil was there and Terrence McKenna was there and Dennis McKenna was there and all these. But there was one point where Tim was speaking and afterwards I was asking him some questions. And I said, do you have any advice for us on how to work with the government and how to bring these psychedelics forward? That's what we're trying to do. I've got this nonprofit for it. We're trying to do this research. What is your advice on how to bring this forward and how to work with the government? And he said, fuck the government. He said, I am so far past asking for permission for anything, but I'm glad that you're doing it. And then he held up my hand like passing the torch. So it was, and that's one of my favorite photographs of me and Tim where he's sort of like, but it was after this, fuck the government. I'm so far past asking for permission for anything, but I'm glad that you are. Now I did follow ups to the Good Friday experiment and I did follow ups, 25 year follow up to the Good Friday experiment, about a 34 year follow up to the Concord Prison experiment. What I discovered in some ways I would say is the key to the 60s, what I just told you, but in the follow up to the Good Friday experiment that I did in the 80s for my undergraduate thesis at New College in Sarasota, Florida, I eventually found 19 out of the 20 people. It was just, that was an enormous challenge because their names were all lost and it just took forever years and years and years to find them all. But I discovered that those people that had the psilocybin experience in the midst of 25 years later with Nancy Reagan and Ronald Reagan, and if there ever were there a social pressure to disavow the validity of the psychedelic experience, that was then. And instead they affirmed it, that they thought with all of this years of hindsight, now looking back, they thought it was a valid mystical experience. But I discovered that one of the persons who had the psilocybin had this experience during the Good Friday service that Reverend Howard Thurman was the minister. He was Martin Luther King's mentor and Reverend Howard Thurman was the minister at Boston at Marsh Chapel. Martin Luther King got his PhD at Boston University. And Howard Thurman had spent time with Gandhi. And so he was really kind of this hidden person behind the civil rights movement about nonviolence as their strategy. But he was interested in the political implications of the mystical experience. So he permitted this experiment to take place. And there were 20 divinity students from Andover Newton in the basement and 10 experimenters, all the people on religion and psychology, like Houston Smith and Walter Huston Clarke and Leary and Ramdas, Mr. Others were there as a support part of it. And the sermon was like three hours later. We actually have, three hours long, we actually have the original sermon from the Good Friday experiment from Howard Thurman up on our website. It's incredible. But part of it was tell people there's a man on the cross. And this one person sort of heard that and he thought, okay, I gotta do that. Howard Thurman was such a dynamic speaker. He said, I gotta tell people there's a man on the cross. And so he said, what am I doing here in this basement chapel listening to this service? I gotta go tell people there's a man on the cross. So he went, they thought he was just going to the bathroom, but he ran out the door. He's running down Commonwealth Avenue and Houston Smith and Tim Leary go after him. And he had thought that since he should tell somebody, he should tell the president, like why not? But then he realized, well, the president's in Washington. I'm here in Boston. I'll just tell the president of the university. So anyway, he's running down the street and Leary and Houston Smith go after him. And he doesn't want to go back inside. They finally get him. He's not hit by a car, but they end up giving him a shot of Thorazine. What's Thorazine? Thorazine is like a major antipsychotic drug. It's a horrible drug, but it knocks people out, tranquilizes them. We would never do that today. We don't abort a difficult experience like that. But in any case, they hid that. That was not part of the writeup of this experiment. So what they did is in a sense, a little bit exaggerated the benefits. It later became out three years later after the experiment or four years in Time Magazine, it said everybody that got psilocybin had a mystical experience. Say it wasn't true, not everybody. Eight out of the 10 did, but not all 10, not this guy. And they minimize the risks. So there was a bit of that. I think Tim was reckless in that way. It was underplayed the risks and overpromised the benefits. And then the Concord Prison experiment, it turned out that Tim had fudged the data completely and it wasn't really successful. So I fault him for that. The outside world was doing the opposite. It was exaggerating the risks and blocking research. So he felt justified to fudge the data because the outside world was fudging in a sense, the response to the. Yeah, yeah, exactly. Yeah, so that presents a very nice context. Fuck the government, but I'm glad that somebody is fighting the good fight from within and doing it the right way, which is where you are. So the 80s, let me ask, what is MAPS, the Multidisciplinary Association for Psychedelic Studies and what is its mission throughout the years, throughout the decades? Yeah, so MAPS is a nonprofit organization. I created it as a nonprofit pharmaceutical company. I created it in 86 after DEA, the Drug Enforcement Administration, criminalized MDMA in 1985. And that was after they started trying to do that in 1984. And as I mentioned, this Terence McKenna is sponsoring, motivating us to do this safety study. So we did that in preparation for this eventual crackdown because MDMA was called Adam, used as a therapy drug, but it was also beginning to be sold as ecstasy as a party drug. And that was taking place in public settings and bars. And so it was inevitable that the crackdown would happen. And so I had a nonprofit connected to Buckminster Fuller, Earth Metabolic Design Lab, that we used to support this lawsuit against the DEA to block them from criminalizing MDMA. We were winning in the court of public opinion and winning in the court. The DEA freaked out and the emergency scheduled MDMA in 85. The handwriting was on the wall that they were not gonna permit the therapeutic use to continue because it gets in the way of the narrative of the drug war and these are terrible drugs. So in 86 is when I started MAPS as a nonprofit pharma because the strategy that I realized is that Americans are open to medicines, that tools to ease suffering, that was the opening wedge, the opening door to changing attitudes. And it would be through science. I would say that my religion is more science than anything else. And culture and religion are metaphorical, but often too much they become literal. But I felt that through science, through medicine, there would be a way to bring these drugs back to the surface. And the mission was always this mass mental health, this idea that what we need is to spiritualize humanity. Einstein said the splitting of the atom has changed everything except our mode of thinking. And hence we drift towards unparalleled catastrophe, which shall be required if mankind is to survive is a whole new mode of thinking. So what is that new mode of thinking? My presumption is that it's more of this mystical sense of thinking that we're all connected. And then if we realize that we're all connected, we're not gonna blow up the world. So a lot of people say that if we could just give LSD all to the world leaders, that would be, then they'd have these spiritual experiences, the world would be better. But I actually had a ketamine experience the day after that DMT experience I described with the inner Hitler. This ketamine experience was, I was above and behind Hitler as he was giving a speech, like the Nuremberg rallies kind of thing. And I was trying to think, how do I get into his head? How do I undo what he wants to do? How can we deal with him? And I realized this whole new thing about the Heil Hitler salute. And he would like push energy out and then everybody would do the salute back to him. And so it's like the one to the many and the many to the one, giving all these people giving away their power and then how it would just sort of ratchet up in intensity like these vibrations. And I realized there's no way to get into his head. This idea we've talked about before about you have to be willing. So what that sort of helped me understand is that the strategy has to be mass mental health. It's not about changing a few leaders. We need to change the mass of humanity to this new mode of thinking, this new spiritual way. So MAPS was a nonprofit pharmaceutical company focused on psychedelics. Big Pharma wasn't doing this work. Government wasn't funding it. So the only source of funds I thought would be through nonprofit donations. And that's been true up until just a couple of years ago now that we have the rise of these for profits. But that's because we've cleared out the regulatory obstacles. We've got more scientific data about the benefits funded through philanthropy. We've changed public opinion and there's a lot less zeal for the drug war. So all of those things have changed. But at the time it was mass mental health was the goal. Two tracks, one was drug development, the other was drug policy reform. So then it's not just available to people that have a clinical diagnosis, but people who are personal growth or they should have access to it as well. I did not know at the time that no drug had ever been made into a medicine by a nonprofit. That was really good I didn't know that. I might've been a little bit more daunted. And actually that didn't happen for 13 more years. It happened in 1999. And that was the abortion pill, RU46, that was approved in Europe, but it's controversial. Nobody, no pharmaceutical company would take it. And it was John D. Rockefeller the third through the population council with the major donor being Warren Buffet. And the Rockefellers and the Buffets and some of the Pritzkers were involved in funding this. So that was the first nonprofit. But the MAPS was designed as from the very beginning, not academic research into psychedelics, but drug development. And that's a fundamental distinction. And that's why I think we're years ahead now with everybody else in terms of making a psychedelic assisted therapy into a medicine. Because our goal from the very beginning was not knowledge, not academic research, it was practical. It was drug development. How do we create new social structures? How do we create legal access to these things? Now, in December of 2014, we created the MAPS Public Benefit Corporation. So MAPS is a nonprofit, but in our 35 years, we've raised about $110 million in donations. What I didn't know when I started MAPS, and it took me quite a few years, I didn't even know this till about eight, nine years ago, was that in 1984, Ronald Reagan had signed a bill to create incentives for developing drugs that were off patent. So MDMA was invented by Merck in 1912. It's in the public domain. These incentives are called data exclusivity, which means that if you make a drug into a medicine that has no patent protection, nobody can use your data for a period of time to market a generic. And that will effectively be, well, it's five years, you do pediatric studies, you get six months extension, and we are being required, if we succeed in adults, to work with adolescents with PTSD. It blocks a generic competitor from applying till that five and a half years is over, takes FDA at least six months to review. So more or less six years of data exclusivity, 10 years in Europe is data exclusivity. So the story then became to the donors that you're not gonna have to give us money forever because we can make money selling MDMA, but we wanna do two revolutionary things, you could say. One is psychedelic assisted psychotherapy, but the other is marketing drugs. When you market it with the profit maximization motive, we end up in the extreme getting the distortions that we have in America, where we have the most expensive healthcare system in the world per capita, but our outcomes are down like 40 or 50 among the countries, our average outcomes. We don't have, third of the people or so don't have insurance, and it's just very inequitable. So what we're trying to do is show a different way to market drugs. And it's a modification of capitalism that's called the benefit corporation, where you maximize public benefit, not profit. You still make a profit. So selling MDMA for a profit is not something we could keep inside the nonprofit because it's taxable, it's a business. So we've created the MAPS Public Benefit Corporation, which is 100% owned by the nonprofit. So we have a nonprofit that owns a pharma company. And the mission of that pharma company is to maximize not profit, but maximize benefit for society. Yeah, yeah. Although there still will be profits, and the profits that we're gonna make are going to be used towards the mission of MAPS, which is again, is this mass mental health and ending the drug war. And in fact, we've hired the Boston Consulting Group to help us plot our commercialization strategy. And so there is some suggestions based, there's so many different assumptions in this, the number of therapists that we train, the price that we set for the MDMA, whether insurance companies will cover it. But there's the possibility of somewhere in the range of three quarters of a billion dollars in profits during this period of data exclusivity, just from the US and we're talking about trying to do this research around the world as well. So that's what the Benefit Corporation is. The Benefit Corporation is our pharmaceutical arm. We're about 130 people now, somewhere in that fluctuates, but one third of them are in the nonprofit. We do harm reduction, psychedelic harm reduction. We help create programs for people with difficult psychedelic experiences at Burning Man, at festivals all over the world, even in cities we're now negotiating with the police, the city of Denver, because Denver has made the mushrooms the lowest enforcement priority. Oregon has passed the Oregon psilocybin initiative. So in those areas where maybe more people are gonna gravitate to do psychedelics, we want there to be harm reduction so that we don't have bad stories coming up that would change that. So MAPS does the psychedelic harm reduction. We do public education. We do a lot of it. That's what you and I are doing right now. We're doing that now. But also research towards. Well, the research now is done in the Benefit Corp. In the Benefit Corp. Yeah, so what happens is people donate to MAPS, get a tax deduction, MAPS transfers the money, or you could say invests in the Benefit Corp. Yes. The Benefit Corp will do the research and then MAPS is the sponsor, but then we will license the sale of MDMA to the Benefit Corp, so. Got it, but the research is done with an eye towards creating something that has a big impact versus just research for knowledge's sake. Yeah, yeah, because I'm interested in political change. The other part of it, which is that the brain is the most complex thing we know in the universe. It's endless. I mean, when are we gonna really, like this idea of, will we figure out telepathy? Will we figure out tapping into the collective unconscious? What is the extents of our brain? How does the brain actually work? Do you ask chemistry questions? So if it's just the pursuit of knowledge, that is an endless thing. And how does that end the drug war? How does that help people directly? So that's why we're focused on drug development more than mechanism of action. Before I ask you about one, but several really exciting studies, let me ask sort of a personal question for me. So if I wanted to get psychedelics from the MAPS Public Benefit Corporation and explore my own mind, how do I get to do that? And when? You won't be able to. You'll never be able to. This is very unfortunate. Because the reason is because the Benefit Corp is designed as a pharmaceutical company. So we can only work on clinical indication. So let's say you come to me and you just say, oh, I'm really depressed. Can I get MDMA to overcome my depression or overcome my PTSD? We'll have to do research in those indications. And by when you say me, you mean like a doctor. So this would be prescribed in theory by doctors. Well, this would go through a doctor and a prescription. Okay, let me ask another question. To further answer, so that's where the drug policy arm comes in, the drug policy reform. So you should be able to get access to psychedelics for your own personal growth. But that's not medicine. So that's why we need to medicalize, to have things covered by insurance, to change people's attitudes, the public attitudes. And then we get this subsequent drug policy reform. And we're talking about it in terms of licensed legalization. So my view is you should get a license to do psychedelics, you get a little education stuff, and then you should be able to buy it and do it on your own. So let me rephrase the question in more specifically. So when can I, if I happen to have ailments of some kind where the doctor decides that psychedelics could help, when would you be a loose estimate for you of when a doctor will be able to prescribe to me something from MAPS Public Benefit Co. And then when for my personal growth and creativity, would I be able to get something? So like, just looking out, this isn't like guaranteed, but like your vision, your hope for, yeah, for psychedelics in society. Well, the end of 2023, so two and a half years from now, we anticipate FDA approval for the prescription use of MDMA for PTSD. Because the FDA does not regulate the practice of medicine, there is what's called off label prescription. What that means, the label is what it's approved for. So the label will say, oh, this is approved for PTSD. But let's say you come and anything else, social anxiety or whatever, you can go to the doctor, they can give it to you. It might not be covered by insurance, they have to be a little bit careful about malpractice. But I think the end of 2023 is when you will be able to do that. Now, there's actually another program, very limited, called Expanded Access, which is compassionate use, which means that, and we have approval for 50 people for compassionate use right now, we think that'll grow. So that's gonna open up in about two months. And so those are people with PTSD, they have to be treatment resistant, nothing has worked for them. And they can access MDMA while we're doing the phase three studies. But they have to pay for it themselves. The sponsor has to pay for all the research. But Expanded Access, because there's no control group, everybody gets the MDMA, people can pay for it themselves. And we think that'll start in a couple months. But it's very limited, it's limited to certain cities. There's also a program called Right to Try, which is passed through Congress. It's similar to this idea of compassionate use, but it cuts the FDA out of it. And patients can negotiate directly with pharma companies to get access to their drugs. That's starting to happen, I think, in Canada now, they're letting people have compassionate access to psilocybin for life threatening illness, because there has been studies with psilocybin for cancer patients and others with life threatening illness. As far as your question about when will you be able to access this for personal growth outside of medicine? I'll take that to mean fully legally, where you can just go buy pure drugs somewhere, when will that happen? We already are starting to see the decriminalization in certain areas of plant psychedelics. And we see overall drug decrim, like that passed in Oregon, so that any drug is now, it's not legal, you can't really fully set up clinics to offer it to people or there's no legal supply like that, but it's decriminalized. So my sense of things is based a lot on watching what happened with medical marijuana and marijuana legalization. So we're sitting here in Massachusetts where marijuana is legal, but what happened first was medical marijuana. So what we see is that medicalization, by demonstrating that under certain contexts, the risks are much less than the benefits, and then there are benefits, and then people hear stories about people that have gotten better, and then that changes their minds, and then eventually that builds up to why are we throwing people in jail for this? Just the culture, yeah. Yeah, so I think that what we're gonna have 2023 is MDMA approved by the FDA, chances are. Psilocybin will be a year or two after that. Then what we're gonna need is a decade of psychedelic clinics that are gonna roll out across America, also other countries as well, thousands of these psychedelic clinics. We already have hundreds of ketamine clinics that are ketamine for depression. More and more people are realizing that ketamine, when it's used with therapy, it's better than when it's not. But the therapists wanna be psychedelic therapists. They don't wanna be a ketamine therapist or an MDMA therapist. So they'll be cross trained. So we will have a decade of these thousands of psychedelic clinics and all these stories of people getting better. And 2035 is when I think that we will move to licensed legalization, which is when you will have the option of just going somewhere once you've done this educational stuff. Potentially, I also think it would be better to have the opportunity for people to go for free, paid for by tax money, to these clinics, and you have your first experience with psychedelics under supervision. And you know what you're getting into. You've, you know, to ask the questionnaire, what the risks are with the drugs, then you get your license. So 2035 is when I think that'll happen. And the clinics will be sites of these initiations. Yes. And so it'd be a safe environment, just like you said, all the things that are actually maximize the likelihood of a pleasant experience and all those kinds of things. It is a frustratingly slow process. And the FDA being part of that process is very frustrating. But of course there's benefits, but boy, I wish it could move a lot faster. Yeah, well, one thing that I've learned from being a parent is that when you have little kids, it seems like they'll be with you forever. But then when they grow up and they go to college and they leave, do you look back and like, where did that 20 years go? Yeah. You know, so we're still dealing with the legacy of the civil war and slavery in America. So actually a 20 year plan is not that long. So while we say it's frustratingly slow, and it is, I mean, it's 50 years since the psychedelic sixties. And right now it's 36 years since MDMA was criminalized. And you think about all those people that committed suicide from PTSD or from anything else. And all those people that could have been helped if the DEA had accepted the Administrative Law Judge recommendation that MDMA stay in schedule three. It's tremendously sad. At the same time, culture evolves slowly. You know, you read the Bible or you read all this stuff, we're not that different from people thousands of years ago. So how are we gonna really evolve enough over the next couple of decades so we don't destroy the planet and don't kill each other? That's why I think psychedelics have an important role to play, that's why I've devoted my life to psychedelics. And it is frustratingly slow. And what I said to myself is our whole effort has not been fast enough. Can we talk a little bit about PTSD and MDMA? There's this fascinating paper came out on a fascinating study that you're a part of. That's a phase three study. Can you describe what the study is? Can you describe what phase three means? Can you describe what the findings are and why it's in fact so important and impactful? Yeah, this study came out May 10th in Nature Medicine. So one of the highest impact factors in medicine, journals, it was tremendous. So to make a drug into a medicine, the first thing you need to do is what are called nonclinical or preclinical studies, meaning safety established in animals. What does the drug do? What are the side effects in animals? Where do you see the risks? And then you negotiate with FDA to do phase one studies. And phase one studies are where you move from animals to humans. And those are more safety studies and trying to describe what the drug does so that you can determine if there is potential medical value there. Certain drugs like cancer drugs are so toxic that you don't have phase one studies in healthy volunteers. That's like phase one slash two, where you bring in the patients, but you still are doing sort of dose response safety studies, but you use patients. But most phase one studies are healthy volunteers. Phase two are where you start bringing in the patients and you start experimenting with various different things. The purpose of phase two is really just to design phase three. Now, again, I'm sort of putting out of the picture in another area is mechanism of action. How do these drugs work? Phase two, you're trying to figure out what they do, who your patient population is, what are the risks, who do you include, who do you exclude, what are the doses, what is your treatment, what are your measures. In our case, it was how do you do a double blind study? That was a big part of phase two. That's a big challenge for psychedelic drugs. Any kind of drugs that have a real strong effect, how do you do a double blind study? The double blind, sorry to interrupt, would mean that the patient should not be aware whether it's a placebo or not. And the researcher. And the researcher is not aware. And so for that lack of awareness, when the effect is really strong, it's very difficult to do on both the researcher and the patient side. Yes, and sometimes they talk about triple blind. So the other part is the raters that evaluate the symptoms and before and after. So you ideally want triple blind. You want the patients, the researchers, and the evaluators of the outcomes, all of them, not to know what the drug, whether it was drug or placebo, and that's to reduce experiment or bias. And then you move to phase three, once you've figured out how to design the phase three studies. And phase three are the large scale multiple studies multi site, placebo controlled, double blind studies, where you must prove safety and efficacy in order to get permission to market the drug. Now, for us, when we started MAPS in 86, as I said, it was one year after the criminalization of MDMA in 85, we had five different protocols that were rejected by the FDA for studying with MDMA. And these were all various phase one studies. They came from Harvard, from UC San Francisco, from the University in Arizona, and Albuquerque, New Mexico, all over. And they were all rejected. 1992, six years after we started, we got the first permission for phase one. And that took us through much of the 90s. Again, things are slow because we have to raise the money through donations. And then in 1999 is when we started the work with PTSD. And that then took us till November 29th, 2016, which is when we had the end of phase two meeting with FDA. So it took 30 years from the start of MAPS to the end of phase two meeting with FDA. And what we had discovered during phase two was several different key points. The drugs that are available right now for PTSD, the SSRIs, Zoloft and Paxil, that have been approved by FDA and regulators in Europe as well, the European Medicines Agency, for PTSD, they work better in women than in men, and they failed in combat related PTSD. All right, so what we learned is that MDMA assisted therapy works just as well in men or women, and it works in combat related PTSD. It works in regardless of the cause of PTSD. We also discovered that even though there are stories that people take MDMA at raves and they dance all night and they overheat and they get hypothermia and they die from overheating, which is true and can happen from pure MDMA, or that sometimes people have heard about needing to cool down and so they drink water and then while they're dancing all night and then they drink too much water and then they dilute their blood and they die from hyponatremia. So there are risks of MDMA, but we discovered that in a therapeutic setting, we can control all those risks, those things don't happen at all. So we discovered safety, we could demonstrate safety. We also figured out that our measure, the CAPS, the Clinician Administrative PTSD Scale, that it's the gold standard all over the world for measuring PTSD symptoms, it's what the FDA and the EMA require. We discovered that it was a good measure for us and that we could show changes in that. The other big thing that we learned is that, and we haven't mentioned this yet, but the work in the 50s and 60s with LSD and psilocybin and the modern research over the last 20 years with psilocybin and classic psychedelics has demonstrated that there's a link between this mystical experience, this unit of mystical experience and therapeutic outcomes for the treatment of addiction, for working with people with life threatening illnesses that for OCD, for Obsessive Compulsive Disorder, that there's with the classic psychedelics, both in the 50 years ago and then the research now has been that there's a link between the depth of the mystical experience and therapeutic outcome. What we discovered is that that's not the case for MDMA, that people do score fairly high on the scales of mystical experience, not as high as they do with the classic psychedelics, but they do score pretty high on average. And a significant number of them have over the cutoff for what would be considered a full mystical experience. So enough to say that we could look at a correlation and we didn't find any. The other thing that we discovered, and this was more humbling, I would say for me personally, is that my dissertation at the Kennedy School, a big part of it was on the, it's about the regulation of the medical use of psychedelics in marijuana. A big part of my dissertation was how to do the double blind study. And I thought I'd solve the problem and I persuaded my dissertation committee that I'd solve the problem. And the solution was therapy with low dose MDMA versus therapy with full dose MDMA. And everybody knows that they're gonna get MDMA, most of these people have never done it before, they'll be confused about is it full dose or low dose. And then the challenge is to pick a dose that's high enough so that there is this confusion, but not so high that it's so therapeutic that we can't tell the difference between the groups. So we studied zero, meaning inactive placebo, 25 milligrams, 30 milligrams, 40 milligrams, 50 milligrams, 75 milligrams, 100 milligrams, 125 and 150. What we discovered is that my dissertation was wrong and that there is no good solution to the double blind problem. What we found is that, to our surprise actually, was that 75 milligrams was an effective dose. We didn't think that. I mean, the normal dose is like, full dose is like 125 milligrams, something like that. But 75 milligrams was an effective dose. And we discovered that the lower doses, so I was half right, you could say, the doses of 25, 30, 40, 50, they could produce enough confusion that you could say that they were successful at blinding, not perfectly, but enough confusion so that people, therapists, couldn't know for sure so that there was this reduction of bias, you could say. But what we discovered, again, to our surprise, was that the low doses made people uncomfortable. They stimulated them, but they didn't reduce the fear. And so people still got better with the therapy with low dose MDMA. But if we gave them therapy with inactive placebo, they did even better than if we gave them therapy with low dose MDMA. So we call it an anti therapeutic effect. I don't mean to imply that they got worse, but it made people uncomfortable. People didn't like it. But we would still help them make some progress. So we had the blinding, but what it meant by reducing the effect of therapy with inactive placebo is that it would make it easier for us to find a difference between the two groups. And so the real question is, if you can do it with therapy, why bother add a drug? So we went to the FDA, and so this was what we discovered during phase two. We went to the FDA at this end of phase two meeting, and we said, we can give you blinding, but it will make it easier for us to find a difference between the two groups. And so we suggest that we do therapy with inactive placebo versus therapy with full dose MDMA. That will cause a problem because most people will be able to tell what they've got. What Tom Loughran, a doctor who used to be head of psychiatry products at FDA is our main advisor. So the first thing he said is that the double blind fails in practice a lot, even with SSRIs, because there's certain side effects that you have with these drugs. And the doctors who are doing these research when you're reporting your side effects, they can say, oh, that's probably, you got the active drug instead of the placebo. So the double blind is in theory is terrific, but in practice, it doesn't always work quite as well. And so what Tom said is that there are two main approaches that they think are important to reduce bias. The first one is easy to do. It's called random assignment. So sometimes there are studies where you'll treat a bunch of people with something and some fraction of them will get better and some won't. And then you say, okay, all those who didn't get better, who volunteers to get this new treatment? And then you give them the new treatment, but the people that volunteer are more likely to wanna get better. They're not representative sample of everybody that has. So when you have random assignment, everybody is similarly motivated and meets the same inclusion, exclusion criteria. So that's what we told, of course we need random assignment. The other part was when the bias double blind doesn't work as well, then the system of independent raters is especially important of how you do that. So we have over a pool of raters, over 20 of them, and we do this monthly interrater reliability tests to make sure that they evaluate this, so that they're given a videotape of a PTSD patient and then they're supposed to rate them according to their symptoms. And then we sort of make sure that we've got this calibrated rater pool and it's all done by Zoom, by telemedicine, and they're randomly assigned to the next person that needs a rating. So they said 20 raters. So we've got like 20 raters and what we wanna do is make it so that each rater sees each patient only once, maybe twice, but not tracking them through the study. So that tries to reduce the bias in the raters that they don't know where this person is in the study. And so there's a fellow, Bob Temple, who's like the old wise man at the FDA. He's been there since 1972. He was in charge of the Office of Science Policy and they brought him into the final meeting of this process where we are trying to design phase three. So once FDA said, yes, you can go to phase three, that was November 29th, 2016, we then negotiated for eight months on the design of phase three and all of the other information that FDA is gonna need. This process of design. To the extent that I have any artistic creativity, it's in protocol design. I really love that. So you enjoy this process. I love it. I love it because it's always trade offs and I acknowledge that we are all biased. And so how do you, there's something beautiful about the scientific process designed to get you to the truth. Especially when that scientific process is trying to get to the truth of the human organism, which is so complicated. So it's very difficult to dissect, to get the strong effects. And when you're analyzing, when you have like raters, they're watching a video. Removing subjectivity from that is very, very challenging. Yeah, very much so. And so we came to this agreement with FDA though that we would use this independent rater pool. And so we learned in phase two again, that the double blind, there was no solution to the double blind problem. And both the FDA and the European Medicines Agency in the end agreed that the best design was therapy with inactive placebo versus therapy with full dose MDMA, accepting the fact that most people will be able to tell whether they got nothing or they got full dose MDMA. Most therapists will be able to tell the difference, but that makes a harder test for us to show a difference between the two groups because we're giving them inactive placebo and not the anti therapeutic effect of low dose MDMA. So once we started phase three, so then we were able to start in 2018 phase three. And the paper in Nature Medicine that just came out was the results of our first phase three study. We came to agreement with FDA that we would do two phase three studies, each would have 100 persons in them. And what the FDA said to us is that they thought that we could prove efficacy with smaller numbers than they wanted to see for safety. The reason they said that is it in phase two, we had a large effect size. So from a statistical point of view, the bigger of an effect that you're looking for, the fewer number of people you need to get statistical significance. When you're trying to find small differences, you need large numbers of people to sort of work out the noise. So we came to agreement on two 100 person phase three studies. And the idea is that it's very possible that the first study would show the efficacy because the effect is so strong. Yeah, yeah, and the second, but also safety as well. So one of the things we also realized when you work with a highly stigmatized drug in the midst of still the drug war and prohibition that we need highly sympathetic subjects and we need to make the best case we can, which means we need to work with the hardest cases so that this is really needed. And so we end up enrolling people. The first study was chronic severe PTSD. And unlike many studies of PTSD, we enroll people that have previously attempted suicide. Wow. So we have multiple people that have tried to kill themselves that we felt like if we were to exclude them, what are we doing? Those are the people that need it the most. So we came to this agreement with FDA. We're gonna work with chronic severe PTSD patients, including those that had attempted suicide. And we would do these two 100 person studies. And we also negotiated what's called an interim analysis. So what that means is that when the study is underway, and often big, big studies, they have this kind of interim analysis where what you do is, and for us, we negotiate when we had 60% or 60 people had reached the primary outcome measure and all 100 had been enrolled, then we would take a look at the data. And if the statistical analysis that we did was showing based on a certain effect size that we chose based on what we saw in phase two, the interim analysis is for what's called sample size reestimation. So what it means is if the results aren't as good as you thought they would, you can add more people. And then you'll get statistical significance. It means that your effect isn't as strong as you thought. It'll be harder to get insurance to cover it, but FDA will still approve it because FDA also believes that these are group averages. There may be some people that will later figure out respond better than others. So they'll approve it if it's statistically significant, even if it has a low effect size. The SSRIs have low effect size. So we did the interim analysis in March of 2020. And what we discovered to our delight was that we did not need to add any subjects. That's all we were told. We weren't told like, what is the results? We were just told all we were gonna get is a number, zero, or you need to add X numbers of people to the study to get statistical significance. That's right around the time that COVID hit and lockdowns happened. And we ended up negotiating with FDA that we would end the study with 90 people instead of 100. It took a while for us to end up doing that. So the paper that we just published is on the results of 90 people. I think it was 46 in the MDMA group, 44 in the placebo group. And what we discovered was that the study worked better than we had even hoped. So the first thing is that you look at statistical significance. You have to get 0.05, which basically means a nickel out of a dollar, a one in 20 chance that the difference between the two groups is due to some random factor rather than to your intervention. And in this case, the placebo group gets therapy and then with inactive placebo and then the group gets MDMA with active placebo. So you have to get 0.05. There's another measure that the FDA uses sometimes called robust, which means one in a thousand, instead of one in 20, one in a thousand. And if you get a robust results, 0.001, and you meet some other criteria, they might agree to approve the drug on the basis of just one phase three study instead of two. Because when you think about it, a one in 20 chance for your first phase three study, a one in 20 chance for your second phase three study, you multiply that together, it's one in 400, 0.025. So that's pretty good. So robust 0.001 is even better than two independent phase three studies, each at 0.05. What we ended up getting was one in 10,000, 0.0001. Outrageous, incredibly. So that's a measure of both the difference between the two groups and the variability. And so what it meant is that we had minimal variability, that most people who got the MDA got quite a large amount of benefit from it. And most people who got the placebo were more or less in the same range as well. That's really exciting, by the way. I mean, I suppose it's exciting from a perspective of approval by the FDA. Maybe perhaps that's the way you're seeing it, but it's also exciting because it has a chance to help people that are truly suffering, yeah. Well, if we can get one in 10,000 in the first phase three study, chances are we can get one in 20 in the second. So it's really gonna be about safety for us in the second phase three study. Now, you can have a large P value, a large significance, but you could have an effect that's not very significant. It's not clinically significant. You can have statistical significance without clinical significance. And as I said, the more people you get in the study, you can find smaller and smaller differences between two groups. Now, we showed that we had a very large effect size. So effect size is based on... That scale you mentioned? Well, the scale of the effect size is based on standard deviations. So an effect size of one means that your results are one standard deviation away from the norm. That's considered very large. The SSRIs, because they were like 0.3, 0.4 effect size, that's considered small effect size. Medium is starting to be around 0.6 and 0.8 and above are large effect sizes. We had what's called placebo subtracted effect size. There's two different ways to look at it. Placebo subtracted means you kind of look at the difference between your two groups. And what that is for us, since one group had therapy and one had therapy plus MDMA, the placebo subtracted effect size is basically the effect of just the MDMA because you've kind of washed out the therapy. That was 0.91. So we had a large effect size, which was different. Wow, so 0.91 over just the therapy, so over the placebo. Yeah. Wow. Now, when we do the within group, meaning the group that just got the MDMA plus therapy, look at their baseline and their outcomes. That's another way to look at it. And that's what's gonna actually happen in practice because people are gonna get MDMA plus therapy. That's 2.1 effect size. Two standard deviations away from the norm is enormous effect size. The other part is that we had no effect by site, which is very important. So we had 15 sites, two in Israel, two in Canada, 11 throughout the United States. The FDA looks at, is there a side effect? Because what that might mean is maybe you've got all your patients or most of your patients going to this one site, which is these highly experienced therapists and they're like hippies from way back and they're super experienced with psychedelics and they're getting great results, but nobody else gets good results. So we had no effect by site. That's incredible. That we've been able to train all these new therapists. We had about 80 therapists working at all these 15 sites. We also discovered that there's a group that's considered to be very difficult to treat, which is called the dissociative subtype. So when people are traumatized, one of the ways to psychologically survive that is you dissociate. It's like you're not there. When you do that though, it's hard to come back because when you come back, then you get all these painful memories and fearful. And so the extreme of that is called dissociative identity disorder, kind of like schizophrenia, almost dissociative identity. So we let people in who are on the dissociative subtype and those are considered to be the hardest to treat because the theory is that you need to be ego intact. As I said, the mystical experience is not correlated with therapeutic outcomes. And you need to be talking about what traumatized you and working through that and expressing it, letting it out, not keeping it in. So the dissociative subtype seems like it's harder for them to get back into the event because they're so dissociated. What we showed is that those people did even better on average than everybody else. So that MDMA is integrative. It helps people who are so separate that they make even more rapid progress. So it's almost like the MDMA made it more difficult for them to dissociate. Yes. Yeah, or you could say it made it easier for them to remember. Yes, exactly. To reverse the dissociation. Yeah. And we find that MDMA enhances memory for the trauma so that you can have these unconscious memories or memories that you cannot remember or that you've suppressed so much, but they distort your view. Your filter of the world is distorted by these fearful memories that the world can't be trusted. People can't be trusted. It's always about to happen. So we find that MDMA increases memory for the trauma, but by reducing the fear, then the memories can come to the surface. Then you can process them, let out the emotions, cry, scream, shake, whatever. And then through this MDMA effect on the amygdala and the hippocampus, it helps you store these memories into longterm storage so that they're not always about to happen. They're in the past. They're part of your story, but they're not the whole story. So we discovered that the dissociative subtype works better. Now, none of this would be enough unless safety. So from a safety perspective, what we discovered is that there was one woman in the study that attempted to kill herself twice during the study. There was another woman that was so worried that she might kill herself, that the therapy brought these things to the surface that she's been pushing away, that she checked herself into a hospital in order to avoid self harm. At the end of the study, what we learned is both of them were in the placebo group. We didn't have anybody in the MDMA group attempt to kill themselves. So the MDMA is really helpful for giving people a sense of hope and that they can somehow process this. Now, it's not to say that nobody will ever commit suicide. That's our big concern in the second phase three study. As I said, it's more gonna be about safety than about efficacy. We think we'll get the efficacy, but we're very concerned about safety. Because we had problems in the first phase three study of somebody trying to kill herself twice in the placebo group, it's the background for having PTSD. So there'd have to be a disproportionate number of people in the MDMA group try to kill themselves or succeed in killing themselves than in the placebo group for the FDA to say, oh, this MDMA, it's too dangerous. We don't think that's gonna happen. So the other findings from safety is that the side effects are transitory. They're minor, they're sweating or jaw clenching or a slight temperature increase. And everybody that's been to a rave knows about it. Take an ecstasy, there are some side effects. But they're minor, they're transitory and there has been this massive problem of during the eighties, the nineties, NIDA, the National Institute on Drug Abuse was trying to say that MDMA was neurotoxic and that you take it and it's gonna cause nerve terminal degeneration. It's gonna be major brain damage. It's gonna be significant functional consequences. And back then they were saying that MDMA is too dangerous. It should never even be researched. Nobody should even get it once because it's poison and brain damage. Well, we no longer believe that, that was exaggerated. That was in service of the drug war. But we've done in phase two neurocognitive tests before and after in two of our different sites and showed no decline in cognitive functioning. So we don't think that there's any neurotoxicity happening and the doses that we use. There's no obvious functional consequences. People are getting better. And the other thing that we've learned in phase two and that we still have to learn from this study. So what we showed is the durability of the effect. We showed that 32% of the people that got the therapy without MDMA at two months after the last experimental session no longer had PTSD. Just with the therapy, which is phenomenal because these are on average 14 years PTSD, one third had PTSD over 20 years. And just with the therapy, 32% no longer had PTSD at the two months. However, those people that got MDMA, it was 67%. No longer had PTSD, more than twice as good. In phase two and in phase three, we're also gonna do the 12 month followup. That's not for the FDA. That's not for approvability. That's more for insurance companies because this is expensive, a lot of therapy time. If it fades, if it's great results initially but then it fades after six months, what's the point? And what we showed in phase two is that people keep getting better. At the two month followup, they're doing pretty well but at the 12 month followup, they're even better. So it's durable. People have learned how to process trauma. They keep getting better. So we've not reached that point in this phase three study where everybody's got their one year followup. But we have also done three and a half year followups to some of the groups that were in phase two and showed that it was durable. And we're doing a long term followup now to many of the people in phase two, some of them treated 15 years ago. So that's all more for the insurance companies. So basically what we found in the paper that we just published is that it was highly efficacious, highly significant, no effect by sight, works in the hardest cases and the safety record was great. That's an incredible success. And that's really exciting, especially given that the people who've committed, who attempted to commit suicide were let into the study. And so these are people who are truly suffering. I mean, that's incredibly exciting. And I mean, just to speak to the frustration why things can't move faster, but for what it is, it's incredibly exciting. Is there other studies of this nature that you foresee enabling that same kind of positive impact, whether it's MDMA for other things like treating addiction, or maybe it's psilocybin for other conditions? Is there something else that's promising? Yeah, I think that what we've discovered I don't think is unique to MDMA. So it's MDMA assisted psychotherapy. MDMA is ideal for PTSD. Maybe it won't work as well for OCD or other things. It was very strategic why we chose MDMA and why we chose PTSD. But I don't think that the results that we've got are so unique to MDMA assisted therapy. I think that psilocybin assisted therapy is gonna be great for people with life threatening illnesses, cancer who are anxious about dying. It looks like it's really good in the treatment of addiction. Again, these are in combination with sort of the psilocybin tobacco is cognitive behavioral therapy with psilocybin. I think that it's gonna be a little bit more difficult, psilocybin for depression. I don't know if it'll be quite as good. There are some biological aspects sometimes to depression, but I think that there'll be really good results for psilocybin for depression. I think it'll be approved. It's considered a breakthrough therapy by the FDA. Ibogaine is phenomenal for opiate addiction, helping people go through withdrawal and then giving them this chance to deal with the material that drives them for addiction. There was Ben Sessa, Dr. Ben Sessa in England did MDMA for alcohol use disorder. And that was really great, the results he got. And it's the case that he ended up basically treating people for trauma. It's the trauma that people run, the emotional challenges that people run from into quieting that pain through drug addiction or alcoholism. So trauma is behind a lot of addiction. I think that we are going to see a revolution in psychiatry and that there will be a lot of conditions that have left a lot of people still suffering that psychedelic assisted therapy, different psychedelics, different approaches. But I think that we will see a lot of hope for psychiatry and psychotherapy and that psychedelics would be a big part of changing the practice of psychiatry and psychotherapy. Yeah, this is really to me fascinating. So I actually, when I was younger, for the longest time, wanted to be a psychiatrist. So I was excited by psychotherapy, but then I perhaps incorrectly, maybe you can correct me, but became more and more cynical because it felt like it was more about prescribing drugs than psychotherapy. I'm not going to correct you. I mean, right now, there is a crisis in psychiatry that there are so many psychiatrists that are so fed up because they have been pharmaceuticalized. They meet people for 15 minutes, they adjust their medications. This is the way they make the most money, but they've lost the art of talking to people. And that's why we see that so many young psychiatric residents are so thrilled by psychedelics that they really want to get back to treating people as individuals, not just a bunch of chemicals. Yeah, that's truly fascinating. Because the reason it was appealing to me, it was a way to study the human mind and to see ways through talking that you can make people feel better, make people better, make people suffer less. And that was really exciting at the time. I ended up then going to AI because then I can understand the mind from that angle. But it's exciting that that could be also revolutionized the field of psychotherapy, take it from its back to its origins, to where a psychiatrist would be a scholar of the mind. Yeah, well, Freud talked about dreams as the railroad to the unconscious. And there was a lot of, you really spent a lot of time with people. Now, right before he died, in his last book, Freud wrote something, and again, this will be a rough paraphrase, but he said that in the future, we may learn about the energies of the brain and there'll be ways with chemicals to influence that that will help the therapeutic process. Yeah. So you could say he was ahead of his time. Yeah. This study paints a fascinating picture of a future where first for medical applications, but then also in general, psychedelics of various forms could be used by the broader society. Forgive the perhaps ridiculous question, but if much of society, including our politicians, are taking psychedelics and dissolving their ego and going through this whole process, how do you think the world may look different in 20, 30, 50 years? Ah, okay, so I said that I think licensed legalization happens in 2035. Yes. And I think by 2050, we will have enough people, hopefully, spiritualized. We're also talking about, we hear so much in terms of climate change about net zero carbon. So our goal is net zero trauma. When do we have a world with net zero trauma? I mean, right now, we have two sites in Israel. So we help a few people, but the recent war with Gaza has traumatized millions of people on both sides. So we are a long way away from net zero trauma. But that's the hope, and that's, I think, possible. I think humanity as a whole is like lemmings heading over a cliff with climate change and with the nuclear proliferation and just the religious hatreds and the more the retreat to authoritarianism and fundamentalism and tribalism. So I think that there's a very good chance, though, that psychedelics used wisely. So it's not just make psychedelics legal and everybody takes them, as you talked about Ted Kaczynski. It's the context that people take it in. But I think that there's a reasonable chance that enough people can, sort of, you could say, clean their filters to see people as more similar to them than different, not to label them as the enemy. Stan Groff, again, had this beautiful phrase about transparent to the transcendent. That's what, so for our ego, can we be transparent to the transcendent? Can the filter that we look through the world at be cleaned to, you could say, cleansing the doors of perception? Can it be cleaned to the point where we can see the humanity in everybody and see that, one way to say this is that, can we get to the point where religions are seen as like languages? Where we all have this need to communicate, there's thousands of different languages, we don't say that this language is fundamentally better than this language, this language is the only right language, everybody must speak English and Russian is bad or German is better. Maybe we'll get to that point that religions are like that, that there are different cultural backgrounds, different symbol systems, different saints and heroes and messiahs and all this, but that, yeah, Jesus is the son of God, but so is everybody. Or the Jews are the chosen people, but so is everybody. So can we get there? I think that we can. And I think that we need to, to survive the challenges that we're facing. And the hope is that by bringing psychedelics as tools forward and trying to bring the context around them to be one of responsibility rather than just profit maximization and just get as many people to do them from all these for profit companies, can we, and then also drug policy reform and embed knowledge in the society, can we get to honest drug education? DARE, the Drug Awareness Resistance Education, is fundamentally twisted. But it's the program that's used in a lot of schools now. So can we get honest drug education, pure drugs, harm reduction, and knowledge about therapeutic uses and on the one hand, and more of these thousands of psychedelic clinics? I'm hopeful and that's our goal. But in this landscape of pharma companies, they make a lot of money. Some people are worried about the impact of those, you know, of big pharma on the landscape of human trauma. Yeah, yeah. So there's, of course, some companies could do good, but that's not inherent, like many of these companies are not optimizing for good, they're optimizing for profit. Exactly, exactly. Does this rise of for profit pharma companies worry you? How do you navigate it? Do we still have for profit companies that basically do what MAPS does, which is like fight the good fight for the benefit of humanity? Like how do we proceed in this, in landscape where drugs can make a lot of money? Well, I am concerned. Overall, I think the rise of the for profit companies, we have to realize is a sign of success, that we have overcome the regulatory prohibitions, we've overcome a lot of the public attitudes that are against it, we've demonstrated some success. So the rise of the for profit companies are a sign of the progress that we've made. On the other hand, turning things over to profit maximizing companies, the big concern is that they're gonna try to minimize the amount of therapy and make it so the cost is less, so insurance companies are more likely to cover it and then that they just sell the most drugs. The other thing we've seen as an example of this is S ketamine by Johnson and Johnson for depression. And it's done by a profit maximizing company. They don't know anything about psychedelic psychotherapy or psychotherapy at all. And so they've gotten approval for S ketamine on the basis of it's just a pharmacological treatment and it's not delivered with therapy, the results fade pretty quickly, so you need to get more ketamine. And so it's designed in a way to maximize the profits for the pharmaceutical company, but it doesn't maximize patient outcomes. What we're seeing though in these various clinics that are being set up is that a lot of people are realizing that it works better with therapy. And so the clinics are run by people that are therapists so that when they provide therapy, they're making more money and then you need less ketamine. Also ketamine itself, S ketamine is a isomer of ketamine that's been patented for depression and they sell it for hundreds of dollars, but ketamine itself is one of the world's essential medicines. It's off patent, it's been around for a long time, it was the main battlefield anesthetic in Vietnam. And it's only a few bucks because it's generic. So a lot of the ketamine clinics are saying, great, thank you, Johnson and Johnson, you've helped demonstrate that ketamine is good for depression, but we're not gonna buy it from you. We're gonna buy it for a few bucks and we're gonna add therapy to it. Now there's a bunch of ketamine mills you could say that are just prescribing the ketamine and people are making a lot of money there. So I am worried about that. I think the best thing that we can do is create an alternative narrative, a different kind of example. We can lead by example. We can't make for profit companies into benefit corporations unless they wanna do that. We can't make them to really maximize patient outcomes. But if we create an example of something that's different, the hope is that people will gravitate towards that and some of the other companies. Like even now we have Exxon and other these companies, oil companies saying, oh, we're big into alternative energy and we're, you know. And that starts with companies that show an example that then communicates to the public that this is something exciting and then they demand the same of Exxon and so on. The public demands it and you could say the same thing for the public demanding the big pharma to optimize for benefit versus optimize for profit and maybe giving power to the therapists, more power to the therapists, more power to the doctors that ultimately want. I think incentives are interesting, but I think doctors ultimately care more because they're in direct contact with humans. They want to make people better. It's not, you know, sure they wanna make money, but they ultimately want to make people feel better because they get to look at people and it's so joyful to make people feel better at the end of the day. So giving more power to them is also perhaps one of the ways that you then incentivize the pharma companies that are trying to do good because the doctors will choose those companies. Yeah, now the other part of this is drug policy reform. So that if we make it so that you can buy MDMA for 10 or 20 bucks on your own and we've trained people on here's our therapeutic method, here is our ways for peer support, then people have an alternative from buying it from the pharma companies. So most of the for profit companies have come to this conclusion that drug policy reform is bad for their business model. I think they're making a fundamental mistake. And I think the reason is that the more that we de stigmatize this, the more that we sensitize people to this is an approach, even when people can get it on their own and do it with their friends or do it with themselves, there's gonna be even more people that say, oh my God, I've got real serious issues. I would rather go to trained professionals covered by insurance. And I think it'll increase the business, but most of the for profit companies don't see it that way. And so as a nonprofit that owns a benefit corp, we're not trying to maximize sales or profits. But I do believe that drug policy reform creates this alternative access point for people and that will help keep the for profits in check to some extent as well. I love it. Let's put on your wise visionary hat and ask when you look to young folks, is there advice you can give to young people today, whether in high school or college about career, about life? You've lived quite a nonlinear and fascinating life yourself. Is there advice you can give either on career or more generally on life? Well, I would say what people often hear is that, we're not actually here for that long a period of time. And the world is on fire. And whether humanity survives is not clear. And how many species are we gonna kill before we figure out not to do that anymore? So I would advise you to really try to develop a combination of what do you need in terms of income for your own survival, but what does the world need in terms of help to make the world better? And Howard Thurman, who we talked about, who ran the Good Friday experiment, the minister there, he said, he's got a famous quote attributed to him. He says, and this is exactly it to young people. He said, there's nothing particular that you should do, but find what makes you come alive because what the world needs is people that have come alive and are passionate. So I would say that be aware of this trap that you need vast resources, that you need all this stuff. I keep thinking of the super wealthy people in first class on the Titanic, as the Titanic is sinking. Their money's not gonna help them. The Earth is like Titanic. We're sinking, we're destroying the planets, destroying the environment. So you need a certain amount of money to be comfortable to be able to do that. You need to be comfortable to not be at that edge of survival, because once you're at that edge of survival, it's hard to think about anything else. But I'd say to young people, to the extent that you're able to do this, and again, student debt and all this kind of stuff is a big problem there too, but really just try to find this combination of what the world needs and what you need. The other thing to say to young people is that life is a lot shorter than you think, and a 20 year plan is not really that long. So if it takes you 20 years to get in a position to do what you wanna do, go for it. Have longterm plans. The other part that was so important for me to keep doing what I've been doing, basically now it's 49 years that I've sort of been devoting my life on psychedelics since I was 18. But when I started, I didn't think it would ever work. I just thought this is the only idea I have in this crazy world, this is what I wanna work on. Luckily, I had support from my family that took care of my survival needs, so I could do that. But I realized that if my happiness was dependent upon accomplishments, that I might never be happy, that I was able to reframe happiness in terms of effort. So if I'm trying hard to get stuff to be better, whether it's better or not, I can be happy at the end of each day, I tried. And so I think you try to separate out the goals that you have and your happiness to whether you're trying hard. The other thing I would say is that everybody has this humanity within them. So be very careful about dividing the world into us and them, and try to... So one of the things that I've done that has taken a long time, because I feel like drugs are illegal. I always felt like the police were the predator and I'm the prey. Yes. But now we're working with the police, and the police have tremendous trauma from the work that they do. We have one police officer who is now going, he's a full time police officer, he's also a psychotherapist. And he's going through our training program to learn how to give MDMA therapy to other police officers. And I met his police chief a couple of times, he got permission from his police chief to go to the second part of our training program, which is where we give MDMA to therapists who volunteer as a patient. So we have just a couple of weeks ago, dosed the police with MDMA. And so I think this idea of those people that are on the quote, other side, try to see through that to their humanity, to what their pains and suffering, what their struggles are, to the extent that you can. And that I think, and build long term relationships. You never know what's gonna come around 20 years from now. So you help some people try to keep these relationships going 20 years from now, something could come. And also be persistent. I think that's been the key to success. I mean, once the FDA or DEA figured out we're not going anywhere, they're gonna have to deal with us, then we started getting some progress. So a mix of patience and stubbornness that gets things done. Is there something you've figured out through your journey with psychedelics about some of the big why questions about life? Like, what the heck's the value of love? Why does it suck so much that we die? And for some of us, maybe it's the Russian in me, but it's quite terrifying, the notion of it. Or the biggest why question of them all, which is what's the meaning of it all? Well, yeah, what I've discovered is that we don't need answers to those questions. That the fact that we can feel happy, that we can love, that we can have moments of happiness, that's enough. Figuring out these big questions, you can get lost in that. And we all can come up with our answers. What's the meaning of life? Why is there life? Why is there consciousness? But I don't know that we need those answers. What we know is that we're social creatures, that other people can make us happy by certain things, we can make other people happy, that one life is enough. So this other part about why is it so tragic that we die? I don't think it's tragic that we die. So first off, if you believe in this collective unconscious, but we have an impact that lasts. But I think that for me at least, I've been of the view that we should be grateful for death, that death makes life precious, that if we had an infinite amount of time, I mean, I'm a bit of a procrastinator about stuff, particularly things that are really hard to do and you just don't do it. And then like, where'd the day go? I was gonna do this. So if we had infinite life, we never died, and would life be precious? Would we do anything? I don't think so. So my parents gave every Jewish new year, they would make their new year's card. And one of the quotes was fantastic. It was just, we have to make up for the brevity of life with the intensity of life. Oh man, that is good. Well, the end makes things precious. Death makes life precious. The end of this conversation makes it precious, and which is a great way to end, Rick. I wanted to talk to you for a long time. I share, you were very excited about the study. I can now understand exactly why this is really promising. This is really exciting, gives me hope about the future, even if it doesn't come fast enough. But like you said, I have to be patient and stubborn. Thank you so much for wasting all your valuable time with me today. It's truly an honor to meet you and talk to you. Not a waste at all. I really appreciated this time together. Thank you for listening to this conversation with Rick Doblin, and thank you to Theragun, ExpressVPN, Blinkist, and Asleep. Check them out in the description to support this podcast. And now let me leave you with some words from Terrence McKenna. Nature loves courage. You make the commitment, and nature will respond to that commitment by removing impossible obstacles. Dream the impossible dream, and the world will not grind you under. It will lift you up. This is the trick. This is what all the teachers and philosophers who really counted, who really touched the alchemical gold, this is what they understood. This is the shamanic dance in the waterfall. This is how magic is done, by hurling yourself into the abyss and discovering that it's a feather bed. Thank you for listening, and hope to see you next time.
Rick Doblin: Psychedelics | Lex Fridman Podcast #202