Welcome to our session on psychedelic-assisted psychotherapy for PTSD, theory, technique, and context. I'm Harold Kudler, psychiatrist with Duke University and the Durham VA Medical Center in Durham, North Carolina. I'll start by saying that our authors have no conflicts of interest to disclose, and thank you for joining us for the presentation. I'm going to be the first speaker, and my subject will be trauma and trance, walking the ghost road from shaman to psychedelic-assisted psychotherapy. We're going to begin with a little bit of history, and I'd like to introduce W. H. R. Rivers, who lived from 1864 to 1922. After completing medical training in 1886 at age 22, by the way, Rivers went on to direct Britain's first experimental psychology laboratory. In 1898, he sailed to the Torres Strait, which is an area comprised of the northern tip of Australia and a number of islands in and around New Guinea, with a Cambridge expedition to study sensory functions of the Melanesians. There he was drawn to anthropological fieldwork. Some of you will remember Rivers as a senior psychiatrist in Pat Barker's Regeneration trilogy, a set of historical novels centered on the treatment of World War I British officers for shell shock at the Craig Lockhart War Hospital outside of Edinburgh. I'd like to read this quote from a later work by Rivers, Medicine, Magic, and Religion. One of the most striking results of modern developments of our knowledge concerning the influence of mental factors and disease is that they are bringing back medicine in some measure to that cooperation with religion which existed in the early stages of human progress. And I want to be sure that I define what a shaman is, because we'll be speaking a little bit about shamanism. This is a picture of the kind of shaman mask that Rivers would have seen in use during his time in Melanesia. In the world of good and evil spirits, typically such people enter a trance state during a ritual and practice divination and healing. Now the beginnings of medical psychotherapy also emerged out of older traditions of trance states and ritual healing in the Western tradition of religion. Father Johann Gesner, who lived from 1727 to 1779, employed the exorcism rites of the Catholic Church to treat physical illnesses. In 1775, Franz Anton Mesmer, a University of Vienna trained physician and academic, delivered an invited presentation to the Munich Academy of Sciences on Gesner's exorcisms, which he went to witness. Mesmer held that Gesner, while being entirely sincere in his beliefs that he was performing a religious ceremony, was actually working the miraculous cures he was capable of through what Mesmer came to call animal magnetism, that it wasn't a religious rite, there was nothing divine in this, it was actually a physical interaction through magnetism. Medical historian Andre Ellenberger cites the intersection between Gesner's religious approach to healing and Mesmer's secular approach as the point of emergence of modern psychiatry. The next step, you know, is that Mesmer began to practice what he called magnetic treatment for a wide variety of physical ailments. Whatever the reason, Mesmer's treatments were strikingly effective in cases in which contemporary medicine failed. As a consequence, Mesmer was in such demand that he needed to optimize the number of people he could treat in a unit of time. And I've shown some pictures of some of the devices he created to do that. In some cases, he inserted metal rods into tables or baths so he could connect magnetically to many people at once. And these people would fall into trances, and when they awoke, would be well. And you see people at the table, for example, in different states of hysterical fits, we might say now. But these were believed to be induced magnetically. And in this magnetic crisis, they would be healed. He also magnetized trees and had his patients tie ropes attached to the trees' limbs. And it's been suggested that Mesmer was literally tying into ancient traditions of pre-Christian tree worship still resonant in 18th century France. Eventually, though, disgruntled members of the French Medical Society petitioned their king, Louis XVI, to begin an investigation of Mesmer and his methods. And that commission, led by Benjamin Franklin, then ambassador to France from the U.S., demonstrated conclusively that there was no magnetism in Mesmer's treatments. Mesmer's theories and his practices were being thoroughly discredited, at least by professional medicine, then remained largely suppressed for a century. The problem is that no one ever stopped to explain why Mesmer's treatments were effective. They sort of, if you will, threw out the baby with the magnetic bathwater. Until this doctor, Jean-Martin Charcot, came along. It was only through the authority of Charcot, known now as the father of neurology, that Mesmerism was welcomed back into the medical arena in 19th century, now as hypnosis. In 1885, Sigmund Freud, then a recent medical graduate of the University of Vienna, came to work in Charcot's laboratory to study neuroanatomy. Charcot's demonstration, shown here in this etching, reminded Freud of a case he'd heard about from his mentor, Joseph Breuer. And just to point out, we're seeing Charcot, and behind him his assistant Bobinsky, of the Bobinsky reflex, and they have hypnotized a woman, put her into a hypnotic state from which she will be able to overcome the hysterical symptoms that led her to be in the hospital. Only temporarily, unfortunately, by the way. Here's a photo of a different woman. Her name is Bertha Pappenheim, and she's photographed actually during her stay at Bellevue Sanatorium in 1882. The time she was being treated by Dr. Breuer. Breuer was trying to treat this young lady for hysteria. She had a number of symptoms, including going into trance states, hallucinations, being unable to drink water, incredible anxiety. Breuer didn't know what to do to help her, but the family had asked and he tried. Having seen demonstrations of medical hypnosis, Breuer tried to hypnotize her, and this came out of his realizing as he sat with her that when she entered a trance state, it looked a lot like the demonstrations of hypnosis he had seen. So he thought perhaps by hypnotizing her, he'd have a gateway to understanding and maybe managing her symptoms. To both their surprise, Anna became completely lucid and free of symptoms while hypnotized, and was able to trace each of her symptoms back to specific traumatic experiences. And as she did so, each symptom in turn disappeared. This was, in fact, the first form of psychoanalysis. Freud tried to do the same kind of treatment with his patients, and he collected a group of patients that he treated using Breuer's technique. And here's some quotes from his very first case of psychoanalysis from Emmy von Oh, from Emmy von N, I should say. So here's Freud discussing the case in studies on his theory in 1895. To this day, I cannot understand how it can be supposed that by merely holding up a finger and saying once, go to sleep, I created in the patient that particular psychical state in which her memory had access to all her psychical experiences. I may have called up the state by my suggestion, but I did not create it, since its features which are, incidentally, found universally, came as such a surprise to me. And later he said, you know, I soon came to dislike hypnosis, for it was a temperamental and one might say, almost say a mystical ally. And Freud didn't want to put his faith in any kind of mystical ally. He moved beyond hypnosis, and psychoanalysis became something he did with someone who was conscious through free association, no longer by analyzing the psyche, by hypnotizing them and delving into their unconscious that way. Even though psychoanalysis moved away from hypnosis, hypnosis trance was called up again in World War II to treat war trauma, a very widespread problem during World War II, as probably it is in all wars. The findings of Army Air Corps psychiatrist Roy Grinker and John Spiegel, working in North Africa early in the war, led to the widespread use of trance as a treatment. That trance could be induced either by hypnosis or by sodium amiton to create states of consciousness which facilitated recovery from psychological trauma. We have in fact here the cover of their book, Men Under Stress, published in 1946. The efficacy of their treatments led to the establishment of departments of psychiatry all across the US in the post-war years, as well as the dominance of psychoanalysis in American psychiatry. A whole generation of American psychiatrists were at war, witnessed the power of these techniques and felt that it was important enough to drive psychiatry forward in the post-war years. The driving force for this movement was that demonstration that the effects of psychological trauma could be effectively relieved by overcoming repression through trance states. And in fact, the psychoanalysts, Grinker and Spiegel, were following Freud's advice given decades earlier that in the face of war, it might be necessary to, if you will, alloy the pure goal of psychoanalysis by bringing other techniques in order to reach a large number of veterans who might need this assistance in the wake of war. If you'd like to be equally impressed, I suggest you watch the Army training film Let There Be Light, which you can Google up on YouTube. Just don't let yourself be hypnotized during the inductions. There was, however, one Johns Hopkins-trained World War II psychiatrist who refused to be converted quite so quickly to psychoanalysis. I think he saw it perhaps as joining a religious cult. Jerome Frank, aided by his daughter Julia in the third and final edition of his work Persuasion and Healing, published in 1991, chose to explore the more nonspecific factors which he believed were the essential elements in all forms of healing, not just in trauma. Frank's statement on the use of psychedelic agents that I'm about to quote is highly relevant to today's discussion. Cultural hostility towards certain drugs limits their use in psychotherapy. Little attention has been paid to the potentially beneficial use of substances that induce abnormal states of consciousness. Widespread prejudice against psychotropic hedonism may be as much to blame as concern over the unreliability of the drug's effects. Frank believed that the healing process across the whole spectrum of disorders primarily worked by restoring morale in people who, as he put it, lacked a sense of inner freedom, self-efficacy, and satisfaction with life. And you might see psychological trauma as, if you will, a paradigm for loss of morale, as defined by Frank. He held that all forms of healing, including those involving various rituals of medication, prayer, and sometimes mind-altering drugs that are intended to provide experiences of direct contact with transcendental healing powers, have in common the restoration of morale. For Frank, morale is restored within and through the therapeutic relationship. And all of the other ways we have of getting there are actually just an overlay on that therapeutic relationship. It is possible that literally all forms that we've created for psychotherapy, which we argue over and have our ways of looking at it, are simply different methods of establishing that healing relationship. So with this truncated history in mind, can we tease out whether the altered state induced by mesmerism, hypnosis, psychoanalysis, and evidence-based psychotherapy, or for that matter a psychedelic substance, or the nonspecific therapeutic relationship, is the core of the therapeutic element in the work that we do with patients? In other words, how can we know the dancer from the dance? To start, we'd need to know a great deal more about human nature and neuroscience, and then be prepared to reappraise our core beliefs and the things our teachers taught us, as good scientists must always do. The closing lines of Pat Barker's Regeneration Trilogy allude to these very same questions and speak to ways in which medical and traditional modes of healing may continue to interweave. Pat Barker's slumped-at-the-night nurse's station struggles to stay awake. On the edge of sleep, he hears Nijuru, the shaman's voice, repeating the words of the exorcism. And there, suddenly, not separate from the ward, not in any way ghostly, but himself in every particular, advancing down the ward of the Empire Hospital, attended by his shadowy retinue, came Nijuru. And these are the words of that exorcism. There is an end of men, an end of chiefs, an end of chieftains' wives, an end of chiefs' children. Then go down and depart. Do not yearn for us, the fingerless, the crippled, the broken. Go down and depart. Oh, oh, oh. He bent over rivers, staring into his face with those piercing, hooded eyes. A long moment, and then the brown face, with its streaks of lime, faded into the light of the daytime ward. And I think as we pursue some of the ideas we'll be talking about, about the use of psychedelics and other treatments that involve trance for psychological trauma, in some ways we have to stare into those same eyes and ask some of these same questions. Thank you. I'd like now to introduce our next speaker, Dr. Mark Bates, who previously served at the Psychological Health Center of Excellence for the Department of Defense in Silver Springs, Maryland, and currently serves as clinical and research psychologist at Aquilino Cancer Center. Thank you, Dr. Kudler, for that rich historical backdrop for this topic. This presentation is focused on MDMA-assisted psychotherapy for PTSD, and it will provide a high-level review of the research and therapy. We believe this is a very timely topic, both given the advances in research and also the popular media attention. If you see below, there's a title from a Fortune posting online, How Psychedelic Drugs May Revolutionize Mental Health. So we want to provide some accurate and most up-to-date information about what is the research status of psychedelic-assisted therapies, treatment components, and treatment mechanisms. Now we're selecting MDMA as an example of psychedelic-assisted therapies, and MDMA is a molecular compound. The significance is really what Dr. Kudler was talking about. It occasions altered states of consciousness, which have a long history in indigenous and clinical practices. And are often associated with increased openness and connection. And in this case, it's combined with a very specific psychotherapeutic approach. We selected MDMA-assisted therapy for PTSD because it has made the most progress in the FDA drug administration, drug development process. Now this process is a very robust process. It's necessarily challenging and long because it ensures the public of the safety and efficacy of a new drug. The process includes three phases, which progressively become larger and larger trials. What I'd like to point out is across each of these phases, there's significant attrition for a new drug application. According to a large study of FDA drug development applications, over 30% attrit out of phase one, over 60% attrit out of phase two, and again, over 30% attrit out of phase three. So you can see it's a very difficult process to go through. MDMA-assisted psychotherapy is now in phase three. In addition, the FDA has given MDMA-assisted psychotherapy for PTSD the breakthrough designation, and we want to make sure that there's an accurate understanding of what this means. It doesn't mean that this is approved as a therapy yet, but what it does mean is based on the FDA's two criteria, it is intended to treat a serious condition, in this case, treatment-resistant PTSD, by definition for which we do not have reliable treatments, and second, that the preliminary evidence indicates potential substantial improvement over available therapy. So now let's talk about that evidence. Now, we'll be referring to evidence from Jerome 2020, which looks at the data pulled from all six phase two trials, both at the after-treatment outcome and the long-term follow-up outcome one year later. The inclusion criteria include a CAHPS 4 score of 50 or greater, and also treatment resistance, which is defined as an inadequate response to a valid duration of psychotherapy and or medication treatment. This sample included over 100 participants. The average time with PTSD was over 15 years, so we are talking about a group of people with serious PTSD. Moreover, the dropout rate was under 8%, which indicates that the active treatment was well-tolerated, especially when you consider the dropout rate for the leading forms of PTSD in the clinical practice guidelines. When thinking about the sessions in this treatment, probably what comes to mind is the dosing session. That session's eight hours long, and this is when the person is using the psychedelics. In this picture, you can see Michael and Annie Mithofer, two of the lead therapists for MAPS, conducting a simulated dosing session with a patient. The patient's lying down with blindfolds and earphones and periodically would be sitting up and conversing with the therapist. In addition, there are very important preparation sessions, which are 90-minute sessions, and then after the dosing session, there are integration sessions, which are also 90-minute sessions. Now, when we put this all together, this is what the flow of therapy sessions look like in the protocol. Three preparatory sessions following the first experimental session, during which the person receives either an active dose of MDMA or a placebo dose, followed by three integration sessions. Each participant can participate in up to three experimental sessions and the average amount of therapy time is around 40 hours. Now, here are the results, and this is looking at the percent of no longer meeting criteria for PTSD. Now, on the left, we see a pie chart for placebo at treatment exit, and we note that 23% just with the psychotherapy have remitted and no longer meet criteria for PTSD, and that's quite remarkable in itself with this population, which means that psychotherapy has distinct value on its own. When we add MDMA to the psychotherapy, we see that 56% no longer meet criteria for PTSD, and then at 12-month follow-up, we see that 67% no longer meet criteria. Now, that's very interesting in that many studies show regression to the mean, but in this case, there's an indication that the value of therapy continues to show an unfolding benefit. Now, if you look at the symptoms in terms of symptom scores, again using the CAHPS-4, what I'd like to highlight here is from baseline to treatment exit, we see a very large effect size with a Cohen's d of 1.58, and again, this is unusual when it comes to PTSD clinical trials, and the significance is 0.0001. I'd also like to point out from treatment exit to long-term follow-up, again, we see the symptom scores going down, and this is actually a significant 0.05 change also. Now, we focused on the PTSD symptoms themselves, but it's also to note that there may be some important benefits beyond symptom reduction. In a qualitative follow-up study conducted by Barone and colleagues and published in 2019, looking at the participants for one of these trials, what they found were the participants reported improved self-awareness in that they were better able to observe their symptoms and cope with their symptoms. In addition, they reported better social functioning and connection, being more interested in engaging in relationships, feeling more confident in relationships, getting more satisfaction out of their relationships. Likewise, increased engagement in new activities or activities they used to enjoy, like painting and music. And for the all-of-us therapists and providers, this is especially interesting, a reduced interest, reduced use of both prescription medication, like anxiolytics and antidepressants, and other substances, a marked decrease in use of alcohol. And finally, more openness to explore treatment options. And this might be new treatment options or going back to treatments that they were already engaged in, like cognitive processing therapy, with renewed confidence and interest in exploring other issues. So, some other contextual factors I'd like to note are that most psychedelics are most psychedelics are currently Schedule I illegal substances, which makes conducting the research and therapy more challenging and expensive and time-consuming. In addition, there are limited opportunities for research participation at this time, which is where people can gain access to this therapy, and limited trained therapists and options for therapists to receive training. And probably one of the most important factors is that this research and therapy really pertains to a specific combination of drug, set, and setting. So, drug, set, and setting is a useful framework to think about what goes into the experience that the participants have. And when we think about drug, it's not just the type of drug, there are multiple types of psychedelics, but especially the quality and the amount of the dose. And then setting is especially important because this is the who, what, when, where, and how that therapy is conducted, both before the dosing session, during the dosing session, and after the dosing session, each which have very important tasks in the therapeutic process. And the setting really sets the stage for the set, and this is the participant's mindset, their mental attitude, their expectancies, especially in the area of perceptions of safety and support. So, applied to MDMA-assisted therapy for PTSD, the drug, MDMA, must meet a very specific good manufacturing standards. And this is important in terms of the strength and purity of the medicine being given. And in stark contrast to what's known as ecstasy, which is a street drug, which may or may not include MDMA, and often includes many other substances. Also, the dosing in this case, for this study, included a primary dose, as well as the offer of a booster dose, which was half of the primary dose. The setting is a highly controlled setting that integrates the manualized protocol. Some of the unique features that will be talked later about is the participants during the dosing session wear eye shades and earphones for part of the time, which help them turn inwards. And then there's the role of music, which we call the hidden therapist. And music plays a critical role during the dosing session in keeping the experience moving along, and also providing evocative periods to help bring up emotional content to process. And finally, the integration is a critical part of helping people retrieve and consolidate much of what happened during the dosing session and integrate it into their daily lives. The setting also is critical in terms of helping the participants feel safe, and especially develop trust. Trust is a critical variable in this process, and it's a variable that evolves over time. It's trust in oneself, and trust in the medicine, trust in the therapist, and trust in the process. Now turning to think about the different types of underlying mechanisms, we can think about different neurobiological and psychological mechanisms. There's a variety of different neurotransmitters involved, and also areas of the brain that are activated. In general, there's a reduction in depression, anxiety, and an increased openness to insights and new perceptions. We see activation of the ventromedial prefrontal cortex can increase regulation of fear, as well as the context for learning. And one of the most important features I'd like to point out is this reduced fear response in combination with increased empathy, trust, and closeness. And in the words of one participant who shared with me, it's like being in a box full of puppies. If you can imagine the warmth and safety and comfort, where you can actually feel safe to bring up things that were otherwise very uncomfortable to expose oneself to. And in talking about mechanisms, finally, this is one mechanism that really distinguishes this type of therapy from other therapies, in that this therapy is focusing on supporting the person's inner healing intelligence by using inner directive therapy, which means that the therapist is following whatever the participant brings up and supporting the participant in being in touch with those experiences, and following where those experiences lead. And we like to use a metaphor of a seed that knows how to grow into a plant, given the right environmental factors, the right soil, the right nutrients, the right watering, the right sunshine. And so the supportive therapy provides that function. So in conclusion, this really is, when you consider the different factors, a unique form of therapy. These factors include the supportive inner directive therapy model that is complemented by the altered states of consciousness occasioned by psychedelic medicines, in this case, MDMA, that help facilitate accessing the inner healing intelligence of a person, which leads to not only a reduction of symptoms, significant reductions, but also increasing aspects of well-being and engagement with life. And the possibility that these benefits can continue to unfold over time. And that may be one area for future studies to consider how to support that. Thank you very much for your attention. And now I'd like to turn the podium back over to Dr. Kudler. Thanks, Mark. That was beautiful. I'd now like to introduce our next speaker, Dr. Robert Kauffman. Dr. Kauffman has retired from a distinguished career as a Navy psychiatrist and is currently affiliated with the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr. Kauffman. Thank you for that very warm introduction, Dr. Kudler. Well, greetings, everyone. It's my distinct pleasure and honor to be able to talk to you today and build on the very excellent presentations we just heard from Dr. Kudler and Dr. Bates. And we'll be hearing from Dr. Yehuda regarding MDMA-assisted psychotherapy. And I'd like to really point out that what we are really discussing during this talk is the relationship between the medicine or the drug MDMA and the actual therapy. I've subtitled this, it's not just the dancer, but the dance and the dance instructor and music too. And I think that will be a good lead-in for Dr. Yehuda's discussion and moderation of our panel. I'd like to thank particularly Dr. Mithoffer and his wife, Annie Mithoffer, for the amazing work they've done over the last decade on MDMA. And they've published much of it. And many of these slides and vignettes are courtesy of those two. I'm going to briefly recap why MDMA-assisted therapy, I believe, is really going to help us enjoy or utilize a very significant and important tool for trauma work. But additionally, I'd like to end with a little vignette, again, courtesy of Dr. Mithoffer. As we've seen, MDMA, or otherwise known as ecstasy on the streets, or MALI, was chosen primarily because of the following principles. It's very short-acting, perhaps six to eight hours duration. It is extremely well-tolerated and with a significant safety record. Unlike other psychedelics, at the doses that it is given, it's not truly a classic psychedelic. In fact, its primary response is emotional. And that emotional response is largely self-compassion, unlike the hallucinations that classic psychedelics produce. And it is, as you'll see, specifically tailored to recovery of deep traumatic memories. And largely this is because of its empathy-producing. And many of you may not necessarily be familiar with an entire class of drugs called entactogens or empathogens. But these are medicines or drugs that can actually create a tremendous sense of unity and communion, oneness, and a profound amount of relationality. MDMA, again, chosen because of its effect decreasing amygdala activity, at the same time decreasing the traumatic memories that are stored in the hippocampus, all the while enabling activation in the ventral medial prefrontal cortex. I should say that MDMA increases hippocampal activity, wherein trauma specifically decreases the availability of those memories stored in the hippocampus. MDMA causes a significant reduction in fear and defensiveness as trauma typically occurs with flooding and making those, in the words of Wessel Van der Kolk, speechless terrors unaccessible. MDMA increases access to these traumatic memories without the kind of flooding and emotional numbing characterized by these speechless terrors. And particularly MDMA, as we'll see, because of its effect with oxytocin, creates a significant amount of trust. And I'm going to mention that again when we discuss the actual psychotherapy and how assisted therapy with MDMA is different. I mentioned the decreased activity in prefrontal cortex, the increased activity of the amygdala in PTSD. Well, basically, MDMA is the absolute perfect drug or medicine because it actually reverses all of those neurophysiologic processes that are blocked or from being processed or being possible mechanisms of action. And this is really one of the take-home points of all of our talks that we really don't know how it is that MDMA actually works. We've not really studied the actual different types of therapies. I'm gonna go into a little bit of what we know, but there's a tremendous amount of work still necessary for exactly what MDMA does to the process of the dance. We do know MDMA promotes fear extinction and allows for memory reconsolidation, which is important for neurogenesis, neuroplasticity, spinogenesis. We're gonna talk a little bit about a class of medicines or drugs called cycloplastogens, which is something that has come on to the scene recently with the use of ketamine. Cycloplastogen is a drug or medicine that's capable of creating a tremendous amount of neuroplastic changes, spinogenesis, plasticity in a very short period of time. We're talking 24 to 48 hours, as opposed to the slow plasticity that occurs with more of the traditional neuropsychotropics and... With respect to the therapeutic approach, again, so much of this work, we owe a tremendous debt of gratitude to Dr. Mitthoff. His wife here are some of the folks from MAPS with whom Dr. Mitthofer worked. But the therapeutic approach really is so is, our mantra is trust, let go, be open. And the task of the therapist is really to, not to understand the problem that the patient or client is facing, but really to help mediate and facilitate the patient or the sufferer's access to a deeper state. As Dr. Bates was talking about, we really wanna tap into what is referred to as the beginner's mind or the inner healer. And we do that by facilitating a environment that the collective unconsciousness is actually allowed to really call the shots. And the collective unconsciousness really is the dancer. And it's really up to the dance instructor to really facilitate this powerful, transformative experience. And it would not be possible without this stage that has been set, both by the set as Dr. Bates was describing, and the setting. The therapeutic approach, as mentioned, is fairly straightforward. The individual is allowed to recline or sit up with eye shades and a music track. And perhaps we can talk a little bit in our discussion period about what music is chosen and why. But it's a non-directive experience. In other words, we call it self-directed. And this is one of the hardest things for a therapist to do, is to really not be a therapist, but really to let the process unfold. And it unfolds nicely with the amount of trust and sensitivity of the therapist. We talked about the power of integration, wherein the experiences are then, if you will, recalled and re-evaluated in joint session with the therapist. We owe this phenomenon of healing intelligence to one of the pioneers, Stanislavs. More slides, and I want to save time for this vignette. I mentioned the importance of a safe and supportive therapeutic setting. Trust, let go, be open. As you can imagine, trust is the fundamental aspect of every therapy. But particularly since the individual has this flood of oxytocin, and hence the interest in aligning in a pro-social way with the therapist, trust is even more significant. And it's really discussed from day one in terms of the conduct of the therapy. Anxiety management is important, as you can imagine with, as we see in prolonged exposure and CBT, there can be a lot of flooding of traumatic memories. So we actually start off with some stress inoculation and stress management techniques, specifically diaphragmatic breathing, sometimes guided imagery, exposure therapy. The trauma always comes up, but it may not come up the first medicine session. It may not come up until the third medicine session. And again, the therapist really allows the inner healer to bring up the trauma, the index trauma, or index traumas when the inner healer is ready. Cognitive restructuring is done largely during the integration. And there's, as you can imagine with the trauma patients that you've worked with, there's always a significant degree of cognitive distortions that the inner healer is capable of identifying themselves. Transference and counter-transference, we typically use a male and female therapist. And that really is important for several different reasons with respect to some of the analytic work that can be done during integration. We use frequently a technique called internal family systems, IFS, to deal with the sense of subtypes or personalities or parts of the psyche. And as we can appreciate those parts of the psyche are frequently compartmentalized or repressed. And then the somatic manifestations, this is very different than a lot of other types of therapies wherein we use either somatic experiencing, sometimes some body work to help relieve blocked expressions of trauma that are sometimes held physiologically or somatic. I'm gonna conclude with a short vignette. This is a story of a Marine veteran. This took place during phase two of the MDMA trial. This particular Marine, two tours in Iraq, indexed trauma. He actually had his Humvee blown up as did many with an IED and witnessed his friend die. He had a tremendous amount of survivor guilt and moral injury. And this is perhaps something that for me as a military psychiatrist is most exciting. And that is the possibility that with the right kind of research, we'll find that MDMA is really helpful in dealing with moral injury. CAP score at baseline, 75. I'll go ahead and read this. You can read along with me. During his first MDMA psychotherapy session, like many participants, this former Marine had anxiety as to the MDMA effects coming on. I had this really intense feeling come over my body and my heart started beating really fast. I started feeling afraid. It felt weird, like when a panic attack came on. Once I started breathing, I felt my heartbeat start to slow down and just relax. I've never felt that before. Amazing how in control I felt of making it go away. After 30 minutes of focused inward with eye shades and headphones, he then described the next experience. This voice, and this is getting back to the idea of these parts and archetypes, this part of me so wise and so intelligent brought this peace over me. And then I tried thinking of that aspect of me that's so rageful. And let me just pause and say, during the preparatory session where we understand what the index trauma is, he described a monster that actually was living inside of him that caused him to be rageful. And of course that monster was his PTSD. And then I tried thinking of that aspect, that monster of me that's so rageful. I realized I have that part of me locked up in jail. I went and opened the door and hugged him and his evil lies faded away. I visualized taking its knife out of my side and taking my hands off its neck. I think I was so afraid of him. I mean, I know it's me, but I described him in that way because I saw what he was capable of in Iraq. He went on to forgive himself and make peace with that warrior I thought was a monster. And we'll talk a little bit about archetypes, particularly when it comes to service members and the warrior. When I think about Iraq now, I feel really peaceful at that part of my journey. I know this is part of the drug, but when I think, am I going to be able to hold on to this understanding? I have now. I think it's so profound that I don't think I could really forget it. Later in the session and in subsequent sessions, former Marine revisited various experiences in Iraq with enhanced recall. When I think about when I got blown up myself, I can really go back and visualize it. I've never been able to visualize it so hard before and really feel what it was like. Following his first session, his wife confirmed that his rage attack subsided. Other symptoms decreased markedly over the ensuing weeks. While I found the healing I needed my very first session, every other session seemed to add more and more. It went beyond Iraq and down into my childhood. I would have profound visions and insights. This drug really facilitates those forgiving experiences. Again, courtesy largely of the way that MDMA works. It feels almost like the inner healer or the MDMA is like a maid doing spring cleaning. And it's as if you thought you were cleaning before, but when you got to things you didn't really want to deal with, you just stick them in the attic. Well, if you're going to clean the house, you can't skip the stuff. His cap score at the primary endpoint was six from 75 and at 12 month follow-up was 19. And there are durability studies continued. This particular individual has continued to come back and maintain significant remission. And on that note, Dr. Yehuda. Thank you, Dr. Kaufman. And now we'll return to our discussion and we're very lucky to have one of the thought leaders in PTSD with us today, Dr. Rachel Yehuda. Dr. Yehuda is at the James J. Peters VA in the Bronx and the Mount Sinai School of Medicine. And she is the director of the newly formed Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai. Dr. Yehuda. Well, thank you very much, Dr. Cudler, Dr. Bates, Dr. Kaufman was really a wonderful set of proposals. And the slide you're looking at here is our logo for our new center. I'm not going to be using other slides because I just was busy taking notes. There was so many, so many stimulating ideas that came up. So let me start with each presentation separately and then maybe we can put some things together from the overview. So Dr. Cudler, it was wonderful to hear your historical overview. And thank you for reminding us that a lot of our new ideas really have very deep roots in history. And it is really fascinating for us not to forget how psychiatry started. And really the question of how you address psychological symptoms and how you even see them really began by seeing these injuries as spiritual wounds and really needing to look towards religion, which we might use spirituality instead right now, but really trying to, but really knowing that there's more to it than just physicality, that there's something else that is needed. And right now the pendulum is swinging back towards trying to even define syndromes that we have medicalized like post-traumatic stress disorder into moral injury. So again, it's this tension between wanting to really objectify something and bring it into a medical domain, but also realize that there's some aspects that are outside that boundary. That really call on something like consciousness, something like spirituality, something outside of us. And you talked about W.H. Rivers, who's a really important and wonderful figure, certainly for those interested in how the field of trauma began. And he really emphasized that this was religion and that he was dealing in a spiritual realm, but again, mesmerism, mesmer really did not like the use of exorcism or any of that kind of language, as you pointed out. And really the heels of modern psychiatry were formed as an attempt to try to scientize this process. And the use of the term magnetism as if there are some kind of physical forces that can be measured, was an early attempt at that. You could see from Mesmer's attempt, the origin of group therapy, or just the idea that groups have a combined energy or there's an efficiency in being able to feed off of those things. So I thought that that was really interesting. Now, the whole time we're talking about the idea that there is something to which people are gravitating, although they don't know the mechanisms. And that's really a very important idea because as you pointed out, Dr. Cudler, just because we don't know how something works, doesn't mean that we know that it doesn't work. And again, this is a real tension in our field, wanting to know how things work before we vet them and not really knowing how to give voice to the things that we can't fully put a mechanism to. And then of course you talked about Freud and you can't have a history lecture without Freud. But Freud actually was a scientist. And although he really understood the power of hypnosis, he also at some point had to concede it's unreliability and distance himself from it. Because again, if it's unreliable, it's unscientific. And so one really wonders all the things that got lost in the history of psychiatry ideas because they just couldn't be captured and studied. And of course, the idea of a psychical state, he knew it, he knew it was real. It just couldn't fully be present. But certainly it is very clear that Freud and his predecessors and people after him understood the power of an altered state and really understood that psychoanalysis, talking, integrating, going deep, required something beyond what could be explained at the time. Now, it's really interesting to bring up the World War II and Brinker and Spiegel and sodium amytol, the idea of being able to create the state with a molecule. That is the beginning of our comfort zone in psychiatry. Be able to really understand that we can have some sense of manipulating this feeling, even though, again, we may not understand how it worked. And I was fascinated by what you said that this led to the establishment of psychiatry departments. Because again, this is our comfort zone. Giving a medication, seeing what the effects of that medication are. And of course, John Hopkins, which is leading the field's efforts by being the first academic medical school to have a psychedelic center. Very interesting that the wisdom happened a lot earlier than that in terms of understanding the importance of substances that induce abnormal states and whether or not these can be exploited for healing. Okay. So you mentioned this idea about, whether it is the altered state that can result in the healing potential or the relationship with the therapist. And Dr. Culler, of course, you knew that this was a false dichotomy and that in essence, what we seek is some form of integration of that. And for decades, we have been talking in psychiatry about how to integrate pharmacotherapy with psychotherapy, but we haven't understood how to do it. And one of the things that is wrong with our current models is at this point in time, most often the person doing the psychotherapy is even a different provider than the person doing the pharmacotherapy. So we know in concept that the two go together, but what's been challenging for us is the integration. And when you talk about the revolution in mental health, which I think, which you did mention briefly, the idea of how much of a revolution is it really when some of our earliest ideas really depended on this kind of integration. So I think that you set up the stage beautifully for Dr. Bates, who really tried to explain and describe the MDMA-assisted psychotherapy and how revolutionary that treatment is right now. And I really appreciated Dr. Bates, how beautifully you laid out the description of MDMA-assisted psychotherapy. But if you'll permit me a process comment, I think that after Dr. Cudler's talk, the first slide with that molecule of MDMA and that picture of the brain, it's almost to reassure us that we are in our comfort zone, that we have molecules and we potentially have brain mechanisms. And so, I think that that is a very interesting way to have brought us back to something that we might wanna wrap our heads about. Now you said something interesting, you said it parenthetically, but I just, I'm a discussant, I can bring it up. And you mentioned that in talking about the criteria for inclusion into the MDMA-assisted psychotherapy trials, which you described beautifully, you mentioned that the patients that were recruited were treatment-resistant. But you also made the point, which I agree with, that our treatments for PTSD might in some way be inadequate. And so, it raises a very interesting question of whether you call someone treatment-resistant if you haven't provided an adequate treatment for them. And I think that this is something that we should really debate in our field. I mean, the term treatment-resistant, it's really a helpful term clinically if the treatments are well-proven. I mean, think about in a medical domain, if a diabetic was resistant to insulin, that would actually give us some information about the need to try something else. But here, this is really a language thing, it really informs our concepts. Because I think a lot of our patients have tried to get better with treatments that may not make them better. And then the question is, is that really a resistance to a treatment? Or is it just not a successful matching between a condition and a treatment? You underscored several really important features of the MDMA-assisted psychotherapy trials and what we have learned from them. And I just wanna review some of them that particularly spoke to me. One of the things that you pointed out was the very large effect size of the treatment, a much larger effect size than we have seen in other treatment trials. And I think that raises the question of what should an effect size be? Not what the statistical effect size should be, but when we think about a therapeutic effect, how much improved do we wanna see a patient before we decide that we've done our job and the patient is improved? And in the field of PTSD, there has been this number on the caps of DSM-IV as a clinically significant or meaningful response. Will a 12-point decline for a patient that starts out with 80 maybe statistically significant? I don't know how clinically meaningful it is to somebody who is suffering. So it really does raise the question of whether we have gotten a little too conservative in our field about how much better we can expect or should expect a patient to be. So we kind of operate in this model of risk management, of trying to hold our patients close so that they don't get worse or they don't fall off of our radar, as opposed to actually really restoring them to a state of somebody that doesn't have that illness. And the other thing that I think is really important is that somebody that doesn't have that illness and the very large effect size that we see in this MDMA-assisted psychotherapy may really serve as a lamp, may actually be a lamplighter to the fact that we can get people to have much better responses than we have allowed ourselves to with other conditions. The other thing you talked about was the low dropout rate, which has always been something that has upset me in the PTSD treatment literature because why are so many people dropping out of our trials? And having conducted some of these trials, I know that this is true. It's not only very hard to recruit patients despite how many patients have the very condition that we're trying to study. But, you know, how do we keep them in the trial? And this therapy seems to do that. The other thing you pointed out, which I thought was fascinating, is that about 23% of the patients who were randomized to placebo also did not have PTSD at the end of the three-month trial. And you made the suggestion that psychotherapy has a distinct value. Well, we'd be very happy if psychotherapy studies resulted in a 23% of patients not having PTSD. I think it's really important to point out the value of maybe eight-hour psychotherapy sessions, which is what happened in these trials, three, eight-hour psychotherapy sessions with opportunity for integration. So even without considering the added benefit of the MDMA, we might be on to... The MDMA studies might be on to something in terms of what psychotherapy should look like. And in 50 minutes, our time is up. May not be enough time for that interview or just to start the conversation that we need to have. And then you mentioned, of course, that people get better over time, which is always what we hope, that we have taught patients how to do something that then they can continue to do on their own. Let's see here. Yes. And let me check my notes here for one second. Right, so you pointed out a lot of the longer-term benefits that our patients have. And you talked also about the importance of set and setting, which is a very critically important point to communicate to an audience that isn't familiar with working with psychedelics. It's the intention that you have when you take a medicine that will really determine a lot of its actions and the condition in which you take the medicine. And heading into Dr. Kauffman's talk, I found that a very, very nice setup for him because Dr. Kauffman began his talk really with trying to ask the question of how does MDMA-assisted psychotherapy work? What are the biological mechanisms? Does it reverse fear conditioning? Does it really cause differences in serotonergic receptors or plasticity and all those things? But when you think about the set and setting and you think about integration, one of the things you immediately have to realize is that traditional ways that we have of understanding how treatment work, which is exploring their pharmacology or looking at brain imaging when people are under the influence of a specific medication may fall short in helping us really understand how to account for the enduring and transformative nature of the experience. And so again, many studies are aimed at giving psychedelics, looking at the fMRI or giving it to animals, looking at what you can see. And I'm sure that those studies have a lot of utility, but one of the important questions that certainly our center is gearing up to answer is why can a relatively short experience like psychotherapy end up providing such long-term and sustained changes? Bob, Dr. Kauffman, you also talked a lot about the inner healer and what goes on in the session with really very good description. And you made a very interesting point about what the therapists do, mostly get out of the way, not impose their own instruction on the patient. But I want to point out that it takes a lot of training to be able to do that. You don't need less training to be able to sit in a psychedelic psychotherapy session with someone. You actually need more. It's actually harder to not intervene. It's easier to follow a manual that has very specific questions and instructions, but it is much harder to be kind of the midwife of a psychological experience. And a lot of things can occur in a session that require extraordinary change, not only training, but a different specific kind of training. For example, patients inner healer might take them to when they were five years old at the time of a childhood trauma or an early sexual trauma. And under the influence of MDMA, patient might dissociate and actually be that five-year-old. Now, in conventional psychotherapy, we learn to ground the patient in the here and now. And an intervention might be, you're here with me now, you're not back there. But in an MDMA session, you actually don't do that. You actually follow the process and say, what do you see? As if you're right there with the five-year-old. So this brings a very extraordinary challenge to our field as we embrace these treatments of therapy, training, retraining, retraining us from a world of now. Many people have not been analytically trained in those times when DSM diagnoses weren't that important, but process was. And most of us have now gotten the kind of training of doing shorter term cognitive behavioral approaches. What are the trainings that we're gonna need to support this kind of process? The other thing just I will focus on, you mentioned that MDMA was chosen for its biologic features, but this is important. MDMA wasn't chosen because of its effects on the brain, because at the time that the studies of MDMA were being developed and being pushed up that hill by the MAPS Corporation, the prevailing idea in science was that of serotonergic neurotoxicity. If you would have looked in the literature in the 80s, when most of the work was trying to be advanced in the 90s, there wouldn't have been a very friendly neuroscience to support the use of MDMA. And it's only now that we're trying to really set things straight. So I think that that is, yep, very, very important to go on to be able to really study the mechanisms that we have. Thank you. Thank you, Dr. Yehuda, that was a wonderful discussion. And I think one of the points I get out of it is that what we're talking about here is important for looking at MDMA and other psychotropics, psychedelic drugs and the treatment of PTSD. But I think you've taken us well beyond that realm to think about where psychiatry is going and where it needs to go by looking at a very long trajectory we're part of. When I think about Bob and Mark who have worked in the Department of Defense and really boots on the ground, when I think of you and me who've had our careers in VA and our work with veterans for many decades of their lives afterward, I find myself thinking back to what Jerome Frank said in 1991, Jerome Frank was an army psychiatrist in World War II and comes home and says, I'm not drinking any particular Kool-Aid. I'm not gonna be a biologist. I'm not gonna be a psychoanalyst. I wanna stand back and understand. That's what we're doing today. And I think when he defined the morale as a sense of inner freedom, self-efficacy and satisfaction with life, I heard then when Mark was talking about the outcome measures, when Bob was giving his vignette, when you were talking about, well, what is it we're trying to accomplish here? I really heard Jerome Frank. And I think we need to be careful that we don't fall into once again, this is the elephant and we're gonna be 500 blind people taking slices and feeling proud that I know what an elephant's like because I know what its ear feels like. It would be wonderful if we could all talk among and respect each other and take this forward. So I'll stop talking and allow any final responses from Mark and from Bob. I'll follow up on, there is so much that you brought up, Rachel, that I believe we could have another presentation just following up. I love this questioning the term treatment resistant. In many ways in our field, we're stuck with the language we have. And I think it was almost an example of a Lillian Bell point that it really is inaccurate and we should be careful how we use that term. So I love the idea of inability to match somebody with an appropriate therapy. At the same time, unfortunately, there has been a lot of research that our frontline treatments and our clinical practice guidelines do work really well for some people, but there are up to 60% that do not respond to those frontline treatments that is what we advocate for people trying. Also this idea about eight hours as part of standard therapy is intriguing. One of the challenges we're running up against is figuring out how to have a sustainable economic model that's reimbursed. So I think ideally we'd wanna explore that. And the idea is how do you support somebody in accessing altered states? I do wonder if just by the process of being eight hours with two extremely caring therapists and listening to music, if people might be accessing an altered state as part of their experience, not the same level as with the MDMA. And then lastly, I just wanna make one more point about this type of therapy because a lot of the manualized types of therapy to me feel kind of cookbook. And this type of therapy, I think you made a point that it actually flows so naturally with what the person's inner healing intelligence is bringing up often in very unpredictable ways in the shape of in Bob's example, the shape of a monster. And then encouraging, and I love Bob's point that fundamental idea of trust, let go and be open. And I like to add and get to know because with these different parts that come up, a really big part of it is instead of the tendency, the natural tendency to avoid is to walk towards the part, to get to know it, to ask it, what do you want to teach me to actually go inside it and look out through its eyes or ride the dragon and experience its world. And it's such a beautiful, powerful process, but it's very different from the standard way that many of us have been taught to do therapy. So just a few comments. Thank you very much. Thank you, Mark. I'll just end by letting folks know that the future is here. Letting folks know that the future is here. MAPS fully expects MDMA to be rescheduled by 2023, possibly even by next year. We've seen from the rescheduling of ketamine and the studies that are going on right now with ketamine-assisted therapy for trauma or PTSD, in addition to treatment-resistant depression and suicidality, that psychedelics are the cornerstone of what is referred to as the psychedelic renaissance. And as Rachel so astutely pointed out that the hardest part is going to be to unlearn what we as therapists have learned. The long pole in the tent is really producing the kind and number of therapists that we are going to need when in fact psychedelics, MDMA principally is rescheduled because this is not easy work. And I would just caution all the therapists out there who might think that the hard part is sitting with someone for eight hours. The hard part, as Mark just pointed out, is really knowing how quiet to be, when to make the kind of integrative interpretations and to always be focused and present during that session, which is very difficult work for therapists. Well, let me simply say, because I think we're out of time now, that this has been a remarkable session. I want to thank you. I think with your help, we may be able to avoid the mistake that Benjamin Franklin made in the 1780s to throw out mesmerism, even though it worked because it didn't fit the science and he proved that his science trumped that science. There was no magnetism. There was no mesmerism. Let's not throw out the baby with the bath water again, and let's open the lens, go to the scanning lens and see if we can help people. I think Franklin's problem was he was not a clinician. I want to thank a group of outstanding clinician researchers for a wonderful talk. Thank you very much. Thank you.

altered states of consciousness

healing practices

psychotherapy

trust

psychedelics

PTSD treatment

MDMA-assisted psychotherapy

safe environment

mechanisms of action

long-term benefits

transformative healing experiences