 But I want to thank the conference organizers and Yost and Nadia, but also everybody here who has been so much fun to talk to. I regularly experience when I go to conferences like this that every conversation that I enter into, I feel welcomed, and it is incredibly interesting and exhilarating. So I want to thank everybody for being here and making this happen. Now wait, I've lost everything. Okay, no, now it's back. So I had originally, could I get a tech moment? It's not changing here though. Okay, forward. Okay. So I originally had quite an ambitious outline for today, and this is what I put into the booklet, but I realized that I had nowhere near enough time to present all of this material. So I'm not going to be talking at all about the history of psychedelic treatment for existential anxiety related to cancer, nor am I going to talk about the training program that we developed at NYU to teach psychedelic therapists. I also want to let you know that I did advertise we were going to be showing a short film, but that's not going to be happening here during this talk. Today, Yost has been kind enough to let us use the Forge Room at lunch to look at these two short films that have eight different participants from the study, and so I urge you to consider coming to that. So instead of doing this, this is the outline for what I'm going to present. First, the study, and then the paper. Now these two obviously have a big overlap, but there's quite a bit of difference between them. First, the study. My computer is not advancing with this. Should I use these buttons instead? Now it's not advancing here, but it's not moving here. It's not moving to the next screen. Right. So I think I'll just use this. And now it's not moving here. Ah! It either advances here, but not here, or here with the clicker. You can close it and you can... Yeah, which slide was it? Right. No, that's okay now. Which slide, Rory? Well, let's go to the beginning, and so I'll only use this. They both work? I think it's working. Okay. Okay, I think I'll use this. It's easier. Okay. So, yeah. Okay, good. Thank you. So we're going to begin with the study on psilocybin-assisted therapy for cancer-related existential distress. Now existential distress is not a diagnosis that you will ever find in the DSM-5, although it is something which you find in patients who have cancer. Existential distress is defined as a loss of meaning or a loss of the will to live. These, of course, can be accompanied by a number of psychiatric symptoms, but they are not the same thing. In our study, we looked for individuals who had existential distress in reaction to cancer diagnosis or treatment, not in reaction to other things that were happening in their life, or also in more generalized anxiety or depression problems. And so this existential crisis in reaction to cancer affected our selection of patients, our preparatory approach, and our integrative approach. Each person that came into the study began with a clinical interview with Steve Ross or Tony Bossis or me or Crystalia Collionzi, who was our research coordinator. So we had a clinical, like first door, where we were looking for existential anxiety. And so everybody who came in fit into other diagnostic categories, but they were not initially chosen to be in those categories. Existential distress results from questioning the very foundations of life and whether this life has any meaning, purpose, or value. So it is a deep philosophical crisis about existence and the meaning of life, not essentially an affective state, although that certainly may be part of it. It's accompanied by anguished thoughts about not existing, being dead, losing a sense of purpose in life, and losing a sense of meaning in life. The severity of existential distress in an individual is not correlated necessarily with the gravity of their cancer, but the meaning of the cancer to that individual and in that individual's life. Now, this kind of distress is common, but in its present cross-culturally, but it is not universally present. It is not a universal reaction to cancer. And there are certain things that are protective against it. Harvey Choshunov described existential distress as a loss of the will to live, a loss of sense of dignity, hopelessness, and the fear of being a burden to others. And David Cassane, who created the demoralization syndrome, described it as the demoralization syndrome as hopelessness, loss of meaning, and a hastened desire for death. And Cassane famously said, targeted therapies to be effective must aim to explore and restore meaning and hope within the context of advancing disease and impending death. So we can hear that this is far removed in the language from symptom reduction, although symptom reduction certainly would accompany that. It's been widely recognized, and the quote that I have here from a chapter by Charlie Grob, Tony Bossis, and Roland Griffiths, that enhanced spiritual or existential well-being may protect against depression and the loss of the will to live and the desire for death. And that meaning is a central concept in spiritual well-being, and the discovery of a sense of meaning in life improves spiritual well-being and quality of life. And for this reason, we established meaning and the rediscovery of meaning as the core psychosocial platform that we used in our study. This is our team, Anthony Bossis, Steve Ross, Alex Belser, who is here. Crystalia Collionzi was our first project manager, then Gabby Agen-Liebus, and now Tara Malone. John Rod Rosen has given us invaluable guidance in all matters scientific and administrative at NYU. Also, I wanna thank Hefter, George Greer, and Dave Nichols for their invaluable support intellectually and financially and in so many administrative ways to getting our study going, as well as Kerry Claudia Turnbull and Bill Linton, who have been so generous in helping us with our study. So, the NYU study is a double-blind placebo-controlled crossover design with two dosing sessions. The entire length of participation is nine months. There's a randomization, which I'm gonna show you more graphically. In a couple of minutes, the crossover point is seven weeks after the first dosing session. There's one dose of placebo and one dose of psilocybin. The psilocybin was 0.3 milligrams per kilogram. The placebo was nice in 250 milligrams, and we had preparatory and integration sessions before and after. This is the exact same information given in a graphic form. During the first month that people were in the study, they had three preparatory sessions, then they had dosing session one, either active drug or placebo. This lasted for six or seven hours in the study room. Then there was a seven-week interim period, during which number of instruments were given to test their symptomatic response, and there were three sessions. Since nobody knew whether there was a placebo or active drug, you couldn't really say whether it was continuing preparation or integration, but we responded sort of intuitively to what it seemed to be needed in the sessions. Then after seven weeks dosing session two, which is the opposite condition of the first, then there are four more weeks of integrative therapy with three sessions, and then the relationship with the study therapist ends. The continuation in the study goes on for a good while longer while a number of instruments and blood work is taken, and the entire study is about nine months in length. The inclusion criteria were cancer with an estimated life expectancy of at least one year. We included individuals without terminal conditions. At first, our study focused on individuals who were terminal, but we discovered that it's quite difficult to get oncologists to say that somebody is both terminal and has a year to live, because they wait much longer before giving that kind of prognosis to someone, and also people who are terminal post certain kinds of problems because they could become ill in a concurrent way or need surgery or become unable to participate in the study. So we included individuals who had cancer, but were not in a terminal condition, and the term life-threatening was expanded. We actually did have some people who were technically cancer-free, but still had tremendous existential anxiety around having cancer, and some people who were in a chronic state of being treated with chemotherapy and being watched and monitored in an ongoing way. So the anxiety disorders that we diagnosed were generalized anxiety disorder and anxiety reaction due to a general medical condition, like cancer, adjustment disorder, and with anxiety and adjustment disorder, with anxiety and depression. You know, we could not diagnose post-traumatic stress disorder or even an acute traumatic stress reaction because by definition in the DSM-5, getting a diagnosis of cancer is not considered to be a trauma. A trauma is something outside the normal realm of human conditions, like rape or being in combat and facing war, but in fact, you do see some symptoms similar to PTSD in patients with existential anxiety. You do see the hyperarousal and underarousal dissociation, hyper-focus, panic reactions being triggered by being near chemotherapy center or seeing anything that would remind them of cancer. So we do see some dissociative-type symptoms, but again, the cancer itself does not qualify as trauma in our DSM-5 diagnosis. So this is yet the same information and this chart you're gonna see again and again because this is where I'm going to put the data from the study. So we have the preparatory sessions. The first vertical column is a niacin or psilocybin and that four months actually is the entire blue bar and that is the amount of time that the therapist and the patient or the participant are in clinical contact with each other. So we have the seven weeks, then the second dosing session and then four weeks afterwards. The psychotherapy platforms that we used included existential therapy taken from the ideas of Irvin Yolom and Victor Frankel, palliative care practices and principles, psychodynamic therapy, family systems therapy and transpersonal therapy. We reviewed the manualized therapies that had been tested clinically and the two that we found to be of the most value in terms of these manualized therapies are the principles of meaning-making psychotherapy by William Breitbart and Sandra Lee, Virginia Lee's meaning-making intervention. And I'm gonna talk just a little bit about each one of those. Victor Frankel is a refugee and a Holocaust survivor and he put forward a type of therapy called logotherapy in which he contends that meaning, that life has meaning and that the will to meaning is the most important drive that we have. And this is quite distinct from a Freudian idea where drives and conflicts are the most central part of the unconscious or a relational psychoanalytic model where attachment and relatedness is the core of what the theory is based in. To Frankel it is finding meaning in life and then when meaning is lost it is the cause of the greatest distress. And according to Frankel, meaning is discovered or rediscovered in a number of ways. One is by creating a work or doing a deed. The second is by experiencing something or encountering someone. And I think it was quite interesting in the course of our work to look at how finding the study and participating in the study became sort of a central experiencing for the people that were involved in it because it really took on a big, big place in their life. And the last point that Frankel suggests is the attitude we take toward unavoidable suffering. And he noticed people in the camps who would take care of one another. He noticed someone who adopted a rat and fed this rat every day and developed a relationship with this rat and found meaning in that, was able to live more fully and be terrified of death less. So there's times when there is inevitable suffering which cannot be escaped and this is part of what the crisis occurs with cancer that you are going to die and you're going to die probably of this disease and sooner than you had thought and sooner than you had hoped these kinds of thoughts evoke this kind of crisis. And he helps people look at how an attitudinal change can make all the difference in the world. This is the cover of Breitbart's and Sharon Papito's book and in particular session four and five. Four is where they write about the attitudinal changes of meaning, how attitude can help acquire meaning and can relieve suffering and then session five is creative sources. Now I think it's kind of false to look at attitude happening in session four, creativity happening in session five, that's not the way that things really work but sometimes in a manualized treatment things have to be put in a schema that suggests that they happen in a certain orderly way but we do our ideas from this book and encourage the therapist to use them. So this is our study room on the right is Bluestone Center for Clinical Research. On the left is where we actually conducted the studies and this blue box says what I'm going to talk about now so I'm going to talk about the three preparatory sessions. The first preparatory session is divided in two. I'm not going to go through this in detail but we do a lot of education where we explain to the participant what's going to happen. We learn about tell them what the medicine might do to them, the role of the therapist, music and so forth and then we switch to encouraging them to tell their story and the life narrative that we take has an emphasis on how meaning is made. You know it was quite heartbreaking to us when we would ask people to tell us about themselves. They would tell us the location of their cancer, the stage of their cancer, the chemotherapy that they had received or the radiation that they'd received and the doctor that they were working with and then they would stop. Like that was the meaning of their life at that point so we saw a very constricted sense of meaning and of course tried to open that out by looking at not just what their diagnosis was but what happened when they got their diagnosis. Who did they talk to? What did they feel? What did they think? How did it change their life? What powerful things happened to them in terms of how their life had had order and meaning and purpose? And this is the beginning of meaning being the central theme. We talk with them about their politics, their social life, their religious values, the source of hope and strength in their life and their hopes, dreams, fears and losses. Okay so this lasted about an hour and at the end of that first hour we do a brief kind of summary. Look, you know, beginning to tell them how we're thinking and hearing and listening to what they're talking about and all of this is in the interest of building a strong therapeutic alliance. During the second session, the preparatory session, we used a structured instrument called the meaning making intervention which was invented by Virginia Lee coming out of the McGill model of nursing. This was a standalone instrument that she developed because she noticed how many of the cancer patients felt the need to be positive, the need to talk about their fears, the need to not be angry, the need to be caretaking of their family members. And I really like this, this is a cover page from her paper, The Extential Plight of Cancer, meaning making as a concrete approach in the intangible search for meaning and it really does deliver in that. So the life review exercise happens like this. You get a big piece of paper and a bunch of pens and markers and pencils and lay this out on a table and you have the participant draw a line from their birth to their death. We don't tell them it's supposed to go from the left to the right but that's how almost everybody did it although a few people drew spirals and as you can imagine, those people never got through all of the information that we were trying to do in terms of like finding out what were the important things that had happened in their life but this is a physician who was like very obedient. He did everything. He even ran out of space, as you can see here. He had to like give himself some more time to include things. And I'm going to show a close up. Again, we were not trying to gather information to write a biography but to encourage the participant to talk about their life and tell us what they thought was important and we can see here doing well in school then he was mean to Scott. He didn't make friends easily. He had trouble making friends. Then he went someplace and started making friends. So as he tells us what his life story is, we begin to learn how he makes meaning and he begins to learn how we listen and how we're building a relationship. The third preparatory session is the one that occurs right before the dosing session. We have what we call the pre-flight checklist. We review intentions although these have been building all the way through. I forgot to say in the meaning-making exercise, sometimes when somebody would describe something, we would ask them what do you think the medicine might do? What do you think the dosing session might be like? So we're trying to listen for transference to the medicine. Does a person have a fearful or excited or a creative relationship that they think that it's going to overwhelm them or they kind of try to control it? So I believe everybody, the therapists as well as the participants, have transference reactions to the medicine and it's part of the creative process to learn what that is so that you can work within it in a really dynamic way. So these preparatory sessions, we teach a breathing exercise to decrease the intensity of the experience if the person is feeling overwhelmed and they're not able to lean into it and really turn themselves over to it in a way that feels safe or at least bearable to them. We talk about the role of the therapists and we give them a trial run with the headphones and the eye shades and the music so that it isn't really foreign to them when that happens. So the dosing sessions, I'm not going to go into a great deal of detail about because we follow the Stan Groff model and we had great training from Bill Richards who came to me with us over a number of times to teach us how to do the sessions and we very much followed the model of working in session that he gave us. It begins about 8.30 or 9.00 and ends about 5.00. We have headphones with a carefully selected soundtrack and throughout the day there is a good bit of Brian Eno as well as a good bit of blood pressure cuff action. So we have an opening ritual. The therapists take meditative position. This is actually the Johns Hopkins dosing room with Mary Cozumano and an identified guy with her. The therapists remain in a meditative, sacred position with focus on the medicine's effects and the participants' immersion in their inner experience. We encourage trust in the medicine's wisdom to show them what they need to see and what's important and they're encouraged to lean into negative states and we actually found this to be really quite easily followed. So many of our participants got this idea and followed this with a lot of courage. Then at the end of the day, we had careful listening to the first journey, the first narrative, including listening to silence and a closing ritual. So at the end of the day, we send them out into the New York night. They write their first narrative of what happened to them during that day. They're assessed for safety before they leave. They go home in a car or a taxi never on foot and we encourage them to contact the therapist if they need to, but basically to have a quiet night of reflection. The integration sessions, there's so much said about them and yet so much that we really don't know about them. I can say that they vary considerably from one therapist to another and I don't think that we have any firm guidelines on what an integration session has to be or needs to be, although I think just about everybody would agree that they're important. So some commonalities, supporting the experiences during the session as real, that they're real experiences, that they are not just dreams that we're entertaining, but that the experiences, the feelings, the perceptions, the observations can be taken as truly real, genuine experiences that belong to the participant to hold. That each element of the journey, including the preparatory sessions and placebo sessions are important and have value. We try to make connections between things that have gone on in the prep sessions with things that went on in the dosing session to start making meaning over time, not just what happened during the psychedelic journey that the person had, but also the entire participation in it because I believe that all aspects of it are really under the spell of the medicine. And lastly, learning from disappointments if necessary. So it would be impossible for me to talk about integration without at least giving some reference to Hans Karl Leunder and psycholitic therapy. Psycholitic therapy, I think, is a somewhat forgotten stepchild of contemporary academic psychedelic research where we have a privileging of the mystical experience with this being the goal and that anything short of this somehow falls short of what the most intense or successful, it's what our therapeutic goal is, it's what we're aiming for. And I don't want to question that as much as the kind of inherent devaluation of what's less than that. And I think it's quite important that we communicate that a psycholitic experience is very powerful and very important and that we regard it with just as much respect and dignity as if the full mystical experience were captured. And it is so poignant how many people said, I'm disappointed because I didn't have a mystical experience or you're disappointed in me. And so we try to work with that and usually that's easily incorporated in their character structure and their character style about being disappointed or being less than. So and it's inevitable that you're gonna have this in psycholitic therapy because there is almost always an emergence of deeply felt highly personal, highly emotional memories that need to be processed. There is decreased defensiveness and an increase in self-knowledge and honesty with the self which has to be processed. Unknown aspects of the self emerge and as we know there's changes in relatedness and sense of connection to other people. And this doesn't just occur to the universe and to the world but also to the therapists and family so that these really sort of primal relationships that are part of psycholitic therapy and not so much, sometimes not paid so much attention to if the goal is on how complete the mystical experience occurred. There's two, this is from Phil Wolfson, Wolfson article in Tukun. He described two different parts or aspects of integration. One is language-based that has to do with talking and understanding and making meaning together and also preserving the mystery of the altered state by not talking about it too much and understanding the idea that telling it to a lot of people or talking about it a lot can somehow turn it into a language-based sound bite or story that you tell rather than having all the many layers of inevitability and mystery that it can hold. So we try to encourage our participants to hold on to that mystery as something which is completely subjectively their own. And then outside language we have the non-conscious changes to the brain and to the mind inviting these to grow through journaling and spiritual practice and meditation which can invite the altered state. One thing that we also do in our integration sessions is play some of the music and have the participant lie down on the couch to help them enter the state of consciousness or at least try to enter the state of consciousness that they found so healing and so powerful with the idea that learning how to enter it without the medicine is a way to access it at any time and that it isn't this sort of precious thing that you go to like a vacation and once you're back from it you can't really go there again. So at the end we have termination. Although there are only nine sessions they occur over a four month period and this is really quite an emotional journey. The attachment is quite intense and for the therapists to the participants as well as from the participants to us. There's usually a ton of gratitude and affection that happens and over time as a therapist you learn to understand someone's attachment style and try to use that understanding to help them with their separation. You want to make meaning relationship with a study and what being in the study has meant to them not just the psilocybin trip but the entire participation in something special and something that is so rigorous and affiliated with NYU. Many of our participants were part of the NYU Cancer Center and so there's this whole transference to NYU as an institution and how what happened in the study was different than what happened at the Cancer Center. We also encourage them to talk about regrets and disappointments because, you know, any therapy where the therapist loves the patient and the patient's not the therapist and everything is all yummy, you know has not gone into some of the deeper, more difficult, hard to face places and so we encourage, try to provide an opportunity to talk about regret and disappointment and often participants will want more sessions or will want to continue working with their therapists and unfortunately neither one of those is something that we could offer to them. And so that's the end of the description of the study and how we work with people. Next I'm going to present the paper and the data from the paper that we have out for publication and hope to be published soon. So this is a title page for the paper with all of the authors. These are the cast of characters that I showed you before but there's two people I want to add who are quite important, James Bab and Barry Cohen. These are our statisticians who helped us whip this data into shape. So these are the inclusion criteria that I've already gone over before. These are the exclusion criteria, the medical illnesses, these really had to be reasonably healthy individuals. There were a number of neurological conditions, altered mental status, dementia, other kinds of cognitive problems that were rule outs, a number of cardiovascular diabetes problems but also antidepressants, mood stabilizers and anti-psychotics. The individual had to be off of all these and really anybody who had bet on an anti-psychotic for a psychotic disorder was eliminated because of the psychiatric exclusion which was a lifetime or a first degree family member with schizophrenia, affective disorder, bipolar disorder, a delusional disorder or other psychotic illness. And the reason for this is the risk of a prolonged psychotic reaction that might follow or triggering unmanageable states and it caused many, many sad moments and broken hearts because there were some people who would have been great candidates for the study who had a brother that was schizophrenic or a sister that was bipolar and of course we don't know that that person would be definitely at risk for a bad outcome but it was part of our caution to work in that way. So after they were brought in, after the clinical screening interviews looking for existential distress, they were given the structured clinical interview for DSM disorders one and two. The first is axis one disorders or so-called biological disorders and axis two are personality disorders. So now I'm gonna go over the primary outcome measures and the secondary outcome measures. First I'm gonna describe to you what they are. The hospital anxiety and depression scale are the heads and the Beck depression inventory. I hope they speak for themselves. Visually all I could do was give you a picture of the outside. We didn't use these manuals but just in the interest of symmetry I put some pictures here. Now this is the Spielberger state trait anxiety inventory. This dapper gentleman is Charles D. Spielberger who invented this widely used instrument state and trait anxiety inventory as you've already heard today. State is how anxious you are right now at this minute. Trait is how anxious are you in general? It's interesting we would think that trait would be consistent over time but participants report variation what they would describe their overall level of anxiety in their life to be. So in this slide I'm showing when we did these assessments. We did the assessments for the primary outcome measures at the very beginning, ground zero. And then this column here is the first dosing session. We did these assessments the day before, the day of, the day after. They were done at two weeks and then they were done at six weeks after dosing one. Then they were done again the day before, the day of and the day after dosing two. And here, six weeks after dosing two and then this is not to scale. These glowing yellow bars are, this six weeks belongs with this arrow and this is at the very end of the study. Now the secondary outcome measures, I'm gonna tell you what those are. These were only done twice. The secondary outcome measures, of which there were a lot, were done two weeks after the first dose and that means if they got niacin, it was done at two weeks and psilocybin, it was done at two weeks. And then at the very end of the study. So the primary outcome measures were done a lot. The secondary outcome measures were done much more infrequently. And now I'm just gonna review in case you're not familiar with what these scales are. The demoralization scale, here I have just a few items from it. I feel emotionally uncontrolled, I feel guilty, life is not worth living. The hopelessness, assessment and illness. This is pretty much self-explanatory but you can see I feel discouraged about my future. I can't have feeling hopeless. I have nothing to look forward to. The death anxiety scale, again I think the title is pretty self-explanatory. It's about how much preoccupation and fear of death that the individual carries. The death transcendence scale measures something quite different. This measures how much transformation in the relationship with death or how much transcendence in the relationship to death that an individual has. I believe in life after death. Only nature is forever. I may die but streams and mountains remain no matter what all of us are part of nature. So we might expect to see lower scores on this before involvement in the study and hopefully an improvement in the death transcendence scale. The next is the World Health Organization quality of life instrument. And this is divided into four domains. Physical, how the person's doing with mobility and their energy and pain. Psychological is how they're feeling and their emotions, social relationships I think speaks for itself and environment speaks for itself. So there are four domains of quality of life and the most interesting or the most relevant for us is the psychological domain because it showed the most change. The facet or the functional assessment in chronic illness therapy is a measure of spiritual well-being and this is divided if you do a factor analysis into two main types of two features. One is religiosity which has to do with actions, going to church, going to services, praying, doing something and a change in your life of your religious life as a result of your diagnosis. Spirituality is much more internal. A positive change because of illness or having a purpose or a mission in life because of that. And then finally, the persisting effects questionnaire and how personally meaningful the experience being here under persisting effects, we say positive effects, negative attitudes towards life, positive attitudes towards the self. So this is a measure of how much these very specific factors have changed over time, the persisting effects questionnaires. And again, the secondary outcome measures were only done twice, two weeks after the first dosing and at the end of the study. So now we're going to look at the study results. We can see 62% of our population were female and the average age was 56.28. 90% were white or Caucasian and we struggled to find a greater diversity among our population, but we weren't able to. I can tell an anecdote here. We did speak with a number of people at the cancer center who are Hispanic and at the risk of an ethnic generalization. Many, many of them, in fact, all of them said to us, yes, I understand what you're talking about and what you're doing, but we don't really need that. We're already there where you're talking because they got the idea that a strong spiritual core would protect them from existential distress and they felt that they already had that. And often we had been referred to them by nurses because they really wanted to give something special to these individuals because they felt so warmly and so kindly to them, but we couldn't enroll them in the study because they didn't have enough distress or there was a lot of anxiety about going outside their religion and going outside the family to do something which felt a little foreign to them. So we can see that 28% had an adjustment disorder with mixed anxiety and depression and 62% had an anxiety disorder with anxiety but without depression. So in our group, there were twice as many people who had anxiety without depression as those who had anxiety and depression, perhaps because of the exclusion of people who were on SSRIs and if they had depression, they would more likely be treated and we were discouraging of people coming off of medication in order to be in the study. We tried that a couple of times and it actually didn't turn out well because over the nine months, the need to restart the medication occurred and then they had to drop out of the study. And 45% were hallucinogen naive. We saw clinically statistical increases in blood pressure at 60, 90, 120, 180 and 240 minutes in both systolic and diastolic and only in systolic at 300. So these were not severe. Nobody needed any kind of blood pressure rescue medicine which we had on hand and there were no serious outcomes as a result of this and these are the kinds of blood pressure changes that we expected. So there were no psilocybin attributed serious adverse effects in our study and the cardiovascular effects that we saw both on heart rate and on blood pressure were orderly, non-clinically significant and they were time related and so we didn't really feel that there was any significant risk in terms of these parameters that emerged. Five or 17% had transient anxiety. This really doesn't quite capture the intensity of it. These were really quite intense anxiety reactions but they were transient and were managed again not with any kind of medication but with breathing techniques and really the participants bearing it and leaning into it. There was elevations in blood pressure and pulse, six or 21% had headaches, four people had nausea, one vomited and there were two individuals with psychotic experiences. So we learned something about using a milligram per kilogram dosage. We had one patient that was very heavy and when you really think about it somebody who weighs 300 pounds does not really have the same blood, does not have twice as much blood volume and brain size as somebody weighs 150 pounds but this woman did get a huge dose and was more severely disorganized in terms of really not being able to communicate and what appeared to be incredible distress. For a long period of time we weren't even able to reach her in terms of her recognizing that we were present and this certainly stirred up considerable concern in me but after it was over she said, no, no, no, it was beautiful and I could tell that you were out there and that you were like worried about me but it was beautiful. So it was such a good example of this discrepancy between the internal experience and what we were seeing because she was agitated all over the place and crunched down and she wore a wig so it was all off on her head and it was really painful to watch and listen and not be able to do anything to even make any kind of contact with her but everybody survived. Nobody was harmed in the running of that subject. So again, no medical and no psychiatric side effects. Now we're gonna get into some pretty hardcore statistics here. I myself have not a career researcher and not a lifelong statistician so before I was involved in this study not only did I not know them that much about statistics but I didn't like I had no idea what a Cohen's D is but I can tell you if you have one that's 2.0 it's small and if you have one that's 5.0 it's medium and if you have one that's 8.0 it's huge, okay? So you have to remember these details because I'm gonna be presenting some Cohen's Ds and so we know that 0.8 is a large one. Okay, so I'm gonna be presenting pre-crossover data. That means this goes from the onset of the study through dosing through six weeks afterwards. So the second dosing here is not part of the data that I'm gonna be presenting now. So again this is pre-crossover and this is really important. The reason it's important is that the pre-crossover data is a comparison data between two groups. So we're looking at the niacin group versus the psilocybin group, okay? So this is a comparison of these two groups against one another. And we can see the green arrow is the dosing day. They started up, oh there it is. So we started here about the same and at this point, not clinically significant, here's the dosing day. This is one day post dosing and you can see the Cohen's D of 1.52. Now what size is that for a Cohen's D? Huge, right? A huge difference, very clinical significant between the psilocybin group and the niacin group and this continues to two weeks post dose and at six weeks post dosing. Here the Cohen's D is 1.71. Again a very, very big effect size compared, this is a very big effect size for psilocybin versus niacin. Here we've broken out the depression. The first one was the hospital anxiety and depression together. This is, okay, we're gonna move forward. Thank you. So this is the state. We can see again a very orderly progression. Here we have the green arrow is where the psilocybin was given and after that there's obvious clinical significance between the psilocybin group and the niacin group and this continues all the way through to six weeks. Again the same phenomenon here. The green arrow is where the dosage was given and each of the data points after that show statistical significance between the niacin and the psilocybin group and the back depression inventory. Again with this one we saw clinical improvement even before the dosing so we can wonder about why that is but afterwards again these large effect sizes at one day post dosing, two weeks post dosing and six weeks post dosing. So now we're gonna be looking, we're leaving the pre crossover and going to the post crossover. The important thing to know in the post crossover is that here we are looking at within group comparisons so we are not comparing the psilocybin to the niacin group. We're comparing each one to where it started. They both started here. The psilocybin group showed some improvement even before the dosing immediately got better after dosing and stayed down all the way to 26 weeks. So this is the end of the study. The niacin group started at the same place improved after the dosing which you would expect with eight hours of listening to carefully selected music and having a therapist be present but then their symptoms returned until they got their dosing and then they showed improvement. This is the anxiety again. This person had some improvement even before their dosing but after it went down and stayed down the niacin group had a little improvement went back up and then after their dosing improved. Same exact pattern in the state. The back depression inventory. You can see the uniformity of these findings here at improvement. This improvement after dosing and it stayed down all the way across to 26 weeks. This group did not show any improvement compared to where it started. I'm sorry I didn't say these open circles mean there's no clinical significance and then we have significance here. This is the mystical state questionnaire and you can see this is during the first dosing session. The red are the niacin participants. The blue are the psilocybin participants and we can see that there's a great significance and the three asterisks prove our p-values for how large this distance is. So going through this very quickly, it's a little bit hard to read so we can see that along demoralization, hopelessness and death transcendent scale, the niacin group at the beginning compared to the psilocybin group 28 weeks later, we see clear clinical significance and improvement. In the quality of life, physical health and psychological showed some improvement and environment but the main thing that improved was psychological. In spirituality there were improvements in meaning and peace and faith and this is again the niacin group versus the psilocybin group at 28 weeks. The persisting effects questionnaire showed improvements in positive attitude towards life, towards self, mood changes, an increase in altruism, positive behavioral effects and an increase in spirituality. So we established safety, we established feasibility. The summary is that there are clear anti-anxiety effects in the acute stage, clear antidepressant effects with large effect sizes in the acute stage. It's much more difficult to make statements about these after the crossover because that creates certain kinds of statistical predictive problems but there's a suggestion that these are maintained up to eight months. So we see improvements in demoralization, hopelessness, death transcendence and spirituality. So psilocybin assisted therapy brought about a remarkable and sustained relief in anxiety and depression symptoms but also remarkably a sustained relief in existential distress. So I'm gonna skip this because I think I'm just about out of time but well I'm gonna talk about it a little bit. This study I've talked about what goes inside but I also wanna talk about the effect that it has. Being involved in this study allowed a number of people to talk with hundreds and maybe even thousands of people about psilocybin, about psilocybin assisted therapy, about psychedelic therapy and in a way the molecule has its spirit being spread all over NYU. As we talked about this and gained an interest and gained respectability and just opened up a discourse of something that had been previously completely unspeakable. And this gave us a groundwork to speak about it, to teach, Steve Ross and I offered a number of courses on psychedelic therapy and psychedelics and psychiatry and it's been inspirational to a large group of medical students and psychiatry residents, one of whom is here, Tanya Sippy, she and I started a psychedelic interest special reading group and last but not least it's helped many individuals with cancer anxiety and their families. I would encourage you if you're interested in this topic at all to come to the Forge Room today during lunch at 12.50 because these two films made by Patrick Henry Murphy show more heart and soul and are just like so deeply moving in a way that I don't think anything that I could have said here today could begin to capture. So these are really, really poignant touching films that encourage anybody who's interested to join us over lunch. I wanna say thank you to the team I work with, to Charlie and Alicia for all of their help and inspiration to Roland and Bill and Matt and Mary and Brian who have given so much to us in terms of inspiration and guidance and collegiality. And I wanna close with this juicy little bit that I found in the paper from 50 years ago. Some of you may know the name of Eric Cast who did a revolutionary work with LSD and pain reduction and this little tidbit from the Chicago Tribune 1966. LSD cheers up dying patient, Dr. Fiennes. And this is a great article that I was gonna talk about in the history but Eric Cast said the drug altered the patient's philosophic and religious approach to life, lifted their moods and reduced their pain. The drug creates a new will to live and a zest for experience which against a background of dismal darkness and preoccupying fear produces an exciting and promising outlook. So how could you say it more eloquently? I wanna thank you for your attention. Thank you, thank you, thank you. Thank you. Come on, come on out very loud. Thank you, thank you. Sorry, questions. Thank you. Thank you for your talk. How much do you think should families be involved in the therapeutic process? I'm sorry, I can't understand your question. Oh, sorry. How much do you think should families be involved in the therapeutic process? And more specifically, do you think it would be reasonable to explore how recordings of the integration and live review sessions could help the family in the grieving process? Did you ask how much I think the therapist should be involved in the integration? No, the families, sorry. Oh, families. Well, we involve the families in the post-dosing, in a short integration session, so the family would come. We did not involve families in those sessions, although I think that a number of times we were, it was to our detriment, because sometimes the families would have reservations or worries, or there was family discord that made the integration, that made the individual going home quite difficult for them, because instead of being in a warm, safe, tender environment, there was discord. So I think that we really missed something important in doing that, and I think it would be a great addition to working with integration. Thank you. You're welcome. Thank you for the talk. So I work in old age psychiatry, so I often see people in their 80s or 90s with existential distress, but they also always have major comorbidities, and they're often on lots of different medications, and looking at your exclusion criteria, I don't think any of my patient group would be eligible for this, and so I wanted to talk to you really about the contraindications and how you arrived at those, and what the stance of the ethics committee was as well about how strict you had to be on your exclusion criteria. Right. Well, I think that you're describing one of the ways that research like this is highly constricted. This was a phase two study, and the goal was to show safety and efficacy. So it was part of our goal to do absolutely everything to minimize negative psychiatric or medical outcomes. But of course, that isn't the way it is in the real world, and so I think that it's one of the ways that this kind of research looks at quite a rarefied individual. These individuals were pretty healthy psychologically because if they weren't, they would either have been on medication or have been in other kinds of treatment or had significant diagnoses that would have excluded them. So I think that when we're looking at a post-rescheduling world, we're going to see that more people are capable of taking these medicines safely, but we also will see more casualties than we saw. It was our goal to have zero casualties because if we'd had any, we might never have been able to move on to phase three, which is one of our goals. So it is something that's somewhat not quite real world about this type of research. I think it also contributes to the way that the therapy is structured because they are so contained in such a complex system and so many people are involved with them that it's really different than if it were one clinician and one participant out in the world. I think that the therapy would be way different if that one individual was responsible for the entire containment of the treatment rather than a dozen people who were involved in containing the individual in the study. Thank you for your brilliant lecture. Just a short question and wish also. The question is, in what magazine this paper is going to be published? In what magazine? This paper is going to be published. That's something which we're still working on. It's still in progress and something which I'm really not able to discuss here. Okay. The wish otherwise is that you will bring this at next year conference at the APA because I think it's a forum to have this data with other colleagues. Thank you. Thank you. Thank you for your interesting talk. You're welcome. I'm interested in differentiated effects of subgroup within your study. You mentioned that 45% of your respondents were hallucinary ignorance, which means 55% were not. Right. Are there any different effects for those groups? And also some of them were religious, other were not. It struck me that you offered also some symbols from Eastern religion to these people. Would it be considerable to adapt to the religion of the people or are there no differential effects for religion at all? Great questions. Most of the people that were, or actually all of the people that had experience with psychedelics had done so in their 20s. And so what we contented with mostly was their memory of that and most of the time their idealization of that and wanting to have something that was similar to that and as profound as that or that they'd done them in a recreational context and felt that it was fun and interesting but not spiritually oriented the way that we were doing it. And I don't think that I saw a difference between the intensity of the effect in terms of how intense their journey was or the therapeutic outcome, but I don't believe that we actually ran data on that question. I know we did have a Buddha, but we tried to have our room be largely nature-oriented, at least pictures of nature. We didn't have any real nature. We tried to grow some plants, but you know how things like that happen in hospital settings. We couldn't really get them to grow too well. But we did strive for a more animist relationship with spirit through nature. And we didn't analyze the relationship between people's religiosity or spirituality and their outcome. Thanks. I'm sorry, but this has to be the last question because we've ran out of time. Feel free to come up to the stage to talk to Jeff in the wild. Please join me in thanking Jeff for an excellent presentation. Thank you. Thank you. Okay. Thank you.