 Thank you very much. It's a great pleasure to be here, a pleasure to be able to open this meeting on psychedelics. What I want to do is talk about the Johns Hopkins psilocybin research project, provide you an overview, a little bit about phenomenology and discuss some of the therapeutic applications. I just want to acknowledge that the research that I'm going to present have been supported by a number of private sector organizations, most prominently the Hefter Research Institute, the Beckley Foundation, one of the sponsors here, also the Riverstik Foundation, another sponsor here, and as well as funding from the National Institute on Drug Abuse. The research I'm going to present has been conducted at Johns Hopkins in Baltimore, Maryland, and I also want to acknowledge that I'm just one of a large group of dedicated and talented research members. Bill Richards, who is here and will be presenting, I think, tomorrow. So I want to talk about psilocybin. It's a naturally occurring tryptamine alkaloid. Psilocybin is the principal psychoactive component in the solospeed genus of mushrooms. Over a hundred of these mushrooms, different species, have been identified and they've been used very likely for thousands of years, certainly for hundreds, by various cultures and structured manners for religious divinatory or healing purposes. I want to just say a little bit about the history. Psilocybin use, its best formal documentation started 16th century Mexico when the Spanish missionaries documented this ritualistic use of psilocybin and the Aztec people, and then they proceeded with missionary campaigns against this what they considered pagan idolatry, in which they literally tried to stamp out the use of mushrooms, they destroyed artifacts, and drove mushroom use ceremonies underground to be rediscovered by Gordon Lawson in 1955, who took psilocybin in Mexico, wrote his account of the psilocybin experience up in Life Magazine. He gave some of the psilocybin mushrooms to Albert Hoffman, the renowned Sando's chemist, discoverer of LSD, some 15 years earlier, and Hoffman identified the primary active ingredient in the mushrooms, psilocybin and psilocybin, and he published his synthesis in 1959, and then the that same year clinical research has begun, and in this day and age when the duration from drug discovery to clinic is measured very often in decades. This is a remarkably short time. So the initial respect for the power of sedent setting wasn't really appreciated. In the very early research, and then in the 1960s, we had the psychedelic 60s, the drug accesses of that era, along with the antics of Timothy Leary at Harvard really ended up undermining the scientific approach and the scientific credibility to studying these compounds, and subsequently they were made illegal, and and there were regulatory and functional hurdles that were erected that that ended up really shutting research down, certainly in the United States and internationally as well. So in the 1990s human research was largely dormant until mid 1990s, late 1990s when several groups in Europe restarted research in earnest, and it was the late 1990s when we initiated our project at Johns Hopkins. So I want to talk a little bit about the abuse and the risks of hallucinogens before going into our laboratory work. So the classic hallucinogens are schedule one compounds in the United States, which means that they're illegal and medically unavailable, and they are functionally as well across most countries and under international law. Lifetime prevalence of non-medical use of the classic hallucinogens LSD and psilocybin is about 17 percent in the United States with about 12 percent, 11 percent for LSD and psilocybin alone. Our National Institute on Drug Abuse in the United States doesn't consider the classic hallucinogens to be drugs of addiction because they don't produce compulsive drug seeking behavior and medical emergencies from the classic hallucinogens are really quite low if you look at prevalence rates in emergency rooms. Several recent analyses from the National Survey on Drug Use and Health in the United States, this is a large epidemiological database, show that the classic hallucinogens are not independent risk factors for mental health problems. And other recent analyses suggest in fact that the classic hallucinogens as a group and psilocybin alone specifically may protect against, may protect with, may have protection with respect to psychological distress and suicidality. However, despite the low abuse potential and the low risk of harm, there still remains concern about non-medical use because of potential adverse effects and these include panic reactions, possible precipitation of enduring psychiatric illnesses and long-lasting visual perceptual disorders. So consistent with this concern, we recently conducted internet survey, large-scale internet survey, asking people to tell us about their most challenging experience after having taken psilocybin. So to be admitted into this survey, people, this was an anonymous internet survey, people had to say they had a challenging or difficult experience with psilocybin and then they were asked to fill out the survey based on their, their most challenging experience, their worst bad trip, if you will. So this is not a random sample. This is explicitly inquiring of people who have had difficult times with psilocybin, tell us about the very worst time you had. So we, the participants, participants were 1,993 people, mean age, 30 years, males and whites over-represented, about almost 40% were daily cannabis users. They were highly educated, 51% college grads and geographically dispersed, 66% from the US, about 60 different countries represented. The people had modest prior use of psilocybin before their the designated experience, so two to five times. So these were not people who had excessive experience. The designated psilocybin experience occurred on average seven years before the survey was completed. So on average the people were about 23 years of age. For those who knew, the dose of dried mushrooms was about four grams, and for for fresh mushrooms that range between 21 and 30 grams, which we estimate to be approximately 20 milligrams of psilocybin comparable to what we give in our studies. That's a moderate high dose range of psilocybin, but we've gone significantly higher than that. So this slide shows the duration of the challenging experience, and it's rated here on a scale from starting at 10 minutes duration, up to 30, 60, 1 to 2 hours, greater than 2 hours the entire session. So, notably here, about 40% of this group said that the duration was two or more hours, which if you think about it, is actually a long time to be stuck in one of these very difficult experiences. And now this shows how difficult or personally challenging was this experience, and this is rated now on a scale like an everyday challenging experience, once a week, once a month, once a year, once every five years. Top ten most difficult of your life, top five single most. So 62% said it was in the top ten or greater, most challenging experiences of their life. And it was almost 40% that said it was in the top five. So this stands out to people as a dramatically difficult point of their life experience. So the degree of difficulty of the experience was greater at higher psilocybin doses, which makes sense, and we've shown in the laboratory, younger age, absence of physical, comforter support, absence of social support, worse emotional state before ingestion. There was some evidence that on average cannabis use before, during the session, was slightly negatively associated with the difficulty. However, written comments suggested that cannabis use sometimes significantly exacerbated challenging experiences. So I think the case about whether cannabis is useful or a hindrance is remains open. Now this slide shows how personally meaningful was this experience. Again, the scale is just like the difficult experience, going from every day to single most, personally meaningful, and 60% of this group is also saying that this is in the top ten most personally meaningful experiences of their lives. So that's curious. There seems to be a paradox there. So it's among the most challenging, among the most personally meaningful. Multiple regression analysis showed the degree of difficulty of the experience actually was positively and significantly related to personal meaning, spiritual significance, and well-being. And so this would appear counterintuitive, you know, unless you think of it as a cathartic kind of experience, and it is consistent with clinical observations that sometimes resolution of psychologically challenging experiences may result in attribution of positive effects. Now in contrast to the degree of difficulty, the duration of the challenging experience was negatively related to personal meaning, spiritual significance, and well-being. So the longer the difficult experience, the less likely there were to be positive attributions to the experience. And so these findings then suggest that therapeutic interventions of challenging experience should be preferentially aimed at reducing the duration rather than the peak difficulty of the experience. And I think that's what the harm reduction groups do in festivals, you know, like Burning Man, the Zendo project. It's about providing comfort and support, significantly reducing duration of difficult experience. Okay, so there were some very noteworthy adverse events that respondents attributed to the experience. So 11% of this group reported that they put themselves or others at risk for physical harm during the experience. And factors that statistically contributed to that were the dose, the degree of difficulty, the duration of difficulty, absence of physical comfort and absence of social support. 3% of this group reported behaving in physically aggressive or violent manners during their experience. 3% got help at a hospital or emergency department. 8% reported decreased sense of well-being or life satisfaction after their experience. So not everyone came away from this experience with positive effects. Now of those whose experience occurred greater than a year before, and this is about 70% of the group, 10% reported adverse psychological symptoms that lasted more than a year, and 8% sought professional help for symptom treatment. So people or some group of these people are seeking out professional help. Respondents who reported having been treated for psychological symptoms before their challenging experiences were more than twice as likely to seek treatment services after their experience than those who had never received psychological treatment. We don't quite know how to interpret this. This is either these people have increased vulnerability to difficult experiences or they're more familiar and treatment services are more accessible to them. Inspection of the data and review of open-ended comments. So this survey had an opportunity for open-ended comments and some people literally wrote pages. I think we have a couple thousand pages of comments from the whole survey. The investigation of those indicated that these challenging experiences were associated with the onset of enduring and impairing psychotic symptoms in three cases and attempted suicide in three cases. So just stepping back, these adverse outcomes are consistent with what are rare reports in psychedelic users of engaging in dangerous behaviors, receiving acute medical care, seeking out psychiatric treatment. However, it's very important and noteworthy that these types of adverse events are very uncommon in structured laboratory settings in which psilocybin or participants are carefully screened, they're prepared, they're supported before, during and after sessions. Okay, so the psilocybin research project at Johns Hopkins, we initiated our first study in 1999. We've completed three studies in healthy volunteers, four large-scale internet surveys, one of which I just described to you. We've done a study in psilocybin treatment of psychologically-distressed cancer patients, and I'll present some of those results. A pilot study of psilocybin-facilitated cigarette smoking cessation. And our ongoing trials include a controlled trial of cigarette smoking cessation. It's a randomized trial. And then we're looking at the effects of psilocybin in long-term meditators, religious professionals, and we're conducting some additional internet surveys. To date, we've treated about 260 participants in over 550 psilocybin sessions, so we've accumulated a good deal of experience. So I want to review the studies in healthy volunteers because they're germane to the treatment application studies. And to do this, what I'm going to do is collapse data across all three studies because the major results I want to underscore are really similar. They represent, in some respects, systematic replications. So we did one study with 36 participants receiving a high dose of psilocybin or a high dose of methylphenidate, another study in 18 participants who received a range of doses of psilocybin, and then a study in 75 participants who had two or three doses and they received a low dose of psilocybin, or some of them did a very low dose one milligram or 20 or 30 milligrams of psilocybin. So volunteers in all of these studies were recruited from the local community through flyers and newspaper advertising. The participants were medically and psychologically healthy. Most were without histories of any hallucinogen use. And we did this intentionally because we didn't want to bias the population toward those people who had had good experiences with psychedelics and then would affirm those experiences. It also gives us information about base rates of difficult experience and naive people. So 129 participants in all mean age 44, 60% female. This is a highly educated population, 92%. Employment, 80% full-time, the rest part-time or semi-retired. These were high-functioning professional groups of people. The volunteers met with our monitors or our guides before sessions and they did this on several occasions before the first session under the rationale that building trust and rapport minimized the risk of adverse effects to psilocybin. Studies are conducted in a comfortable living room-like environment. Volunteers come into our unit at 8 in the morning, swallow a capsule. There are two guides or monitors present throughout the session. This is Bill Richards, incidentally, who you'll hear from later. The volunteers encourage to lay on the couch, use eye mask and headphones through which they listen to a program of music. And they're encouraged to direct their attention inward on their inner experience. If fear or anxiety arise and the guides or the monitors are there to provide reassurance. So this shows the time course of monitor ratings in the dose-effect study. And I show this to show the orderliness of this data. I've done a lot of drug research in my life and rarely do I get something as beautiful as this in terms of the order of doses and time dependence. So this is ratings of magnitude of overall drug effect as a function of time across the first six-hour period here. Onset occurs at 30 minutes, peak effects at 2 or 3 hours, and decreasing toward baseline levels thereafter. So not surprisingly, under these conditions, when you give psilocybin, a classic hallucinogen, we get perceptual changes like visual illusions, greater emotionality like increased sense of joy or peace or contentedness, and less frequently, but it does indeed occur, fear and anxiety. There are also cognitive changes, sense of meaning, sometimes suspiciousness emerges. But to me, the most interesting effect and one that we've pursued and really I want to highlight throughout this presentation, is that in most volunteers psilocybin under these conditions produce large increases on self-rated questionnaires designed to measure naturally occurring mystical type experiences. These are experiences reported by religious figures throughout the ages. And this slide just shows from the dose-effect study, nice dose-related increases on the mystical experience questionnaire when this questionnaire is given immediately post-session. So what is a mystical experience? In fact, the phenomenological dimensions have been well described prior to this research. We've actually now developed psychometrically valid instrument to measure these. But just descriptively, the dimensions of this experience are these. The core features this sense of unity, this interconnectedness of all people and all things, the sense that all is one, pure consciousness. And that's accompanied by a sense of sacredness or reverence. There's a noetic quality, a sense of encountering ultimate reality, a sense of the authoritative truth of these experiences that emerges. Deeply felt positive mood, sometimes experiences universal love, joy, peace, transcendence of time and space, present or past and future collapse into the present moment, space becomes endless, the void. And they're often characterized as being ineffable. One of the first things people say at the end of these sessions is they can't possibly put it into words. Now, by the end of the psilocybin session, the acute effects of psilocybin have totally resolved as a relatively short-acting compound. The feature that's so interesting is that the memory of these experiences endure. So this is now one month after sessions and we're asking people to do various ratings. And you can see that about 80% say it's in the top five most personally meaningful experiences of their lives, comparing it to the birth of a child or death of a parent. Over 83% are saying it's in the top most spiritually significant experiences of their life. 94% increase sense of well-being or life satisfaction moderately or very much. About 90% endorse positive behavior changes. So that's one month. And this shows the kinds of adjectives that people are endorsing to affirm positive attitudes about life and self. So people are saying of these experiences, they have increased sense of personal authenticity, playfulness, creativity, mental flexibility, self-confidence, increased life meaning, appreciation, richness, positive values and trust. And likewise the positive changes in emotion occur and people are endorsing here, increased love and open-heartedness, inner peace, joy, inspiration, decreased sadness and depressed mood, anxiety, anger and guilt. And this incidentally, the decreased depression and anxiety relates directly to some of the therapeutic applications. That was one month. Now here's 14 months follow-up and that's as far as we've gone in follow-up but my impression is that if we end up doing further follow-up, these effects are sustained. But here is the endorsement of increased personal well-being or life satisfaction. This is the low dose of psilocybin and the high dose of psilocybin. So you have, this is being endorsed by 94% of the volunteers five weeks after high doses of psilocybin and this is maintained at 14 months. This shows an interesting relationship between the mystical experience as measured immediately after the session and the prediction of positive outcome 14 months later, in this case predicting the spiritual significance of the experience. So this panel is showing this is mysticism score right after sessions. This is spiritual significance over a year later, 14 months. You can see there's a strong correlation. So there's something about what's captured in that mysticism scale that's predicting long-term positive attributes. This does not occur with simple intensity of the psilocybin experience. So it has something to do with the qualitative nature of this experience. We also interviewed friends, family members, colleagues at work to see if we could validate the kinds of changes that people were reporting personally. And indeed we did. In this study this is just showing that at one month follow-up and 14 month follow-up, the community observers are showing changes of the same type or analogous to what the volunteers are reporting. So this is in their own words at 14 months. What is it that people are remembering? This is one person. The part that continues to stick out for me was the knowing scene and experiencing with every sense and fiber of my being that all things are interconnected. The sense that all is one, that I experienced the sense, the essence of the universe and the knowing that God asked nothing of us except to receive love. Another one, the feeling of no boundaries where I didn't know where I was, where I ended and my surroundings began. Somehow I was able to comprehend what oneness is. So soberingly, in spite of the selection and preparation and support we provide, about one third of our volunteers that are very high dose of psilocybin, that's 30 milligrams per 70 kilogram, none after placebo or methylphenidate, reported strong or extreme ratings of fear sometime during the session. The fear and anxiety had an unpredictable time course of onset and duration. So this really underscores the importance of having that social support and the rapport and trust with the monitors or guides. About 25 percent of our volunteers had some mild transient paranoid thinking ideas of reference sometime during the session. However, and this is the most important point, despite these struggles, most participants rated the overall experiences having personal meaning and spiritual significance. And no volunteers from our healthy volunteers group rated the experiences having decreased their sense of well-being or life satisfaction. So under appropriate conditions, we don't need to have the adverse events that occur rarely but sometimes under uncontrolled conditions. So what can we conclude from the healthy volunteer studies to date? So psilocybin can be administered safely. Safely psilocybin can occasion mystical experiences in the majority of people studied. And these studies, and I didn't go into it, provided significant controls for expectancy effects. These effects are dose dependent, specific to psilocybin versus psychoactive psychocontrol. They're rated as profoundly personally meaningful and spiritually significant and produce enduring positive changes and attitudes, moods and behaviors. So there are many different directions that research can go and I'll return to this slide at the end. But what I want to do now is transition into potential therapeutic applications. Are there therapeutic benefits to such experiences? And I'll present data from two in a cancer trial and then smoking cessation trial. So anxiety and depression is a significant problem in cancer patients. It often leads to a very negative impact on quality of life. Existing pharmacological and psychological treatments are really quite limited. There's some existential psychotherapy approaches that have some value. But by and large we don't have very good interventions for this kind of distress. Several promising trials were conducted in the 60s and 70s with LSD and another classic hallucinogen. And Charlie Grove and Alicia Danforth who is also going to be presenting at this meeting did a pilot study with a moderate dose of psilocybin published in 2011. So the goal of this study was to determine the efficacy of a moderately high dose of psilocybin. This is 22 milligrams per 70 kilograms. So in our dose effect study this is on the high intermediate range when administered under supportive conditions to patients with a life threatening cancer diagnosis and clinically significant anxiety and depression. So it's a randomized double blind crossover design examining the effects of psilocybin dose high versus low on various outcome measures. Mean age there are 51 participants who completed at least one session mean age 56 about half female highly educated again predominantly Caucasian 45% had some lifetime history of hallucinogen use. But on average this was 31 years ago so these were not people who were had current ongoing use. Medical prognosis at the time of diagnosis 65% had recurrent or metastatic disease 35% possibility of recurrence. The types of cancers were varied we didn't select any given type of cancer just had to be a form of life threatening cancer. This slide shows the DSM psychiatric diagnosis and prior treatment so 37% had fulfilled criteria for depressed mood 31 for anxiety. 31% for mixed anxiety and depression and about half had received prior medication treatment for anxiety and depression. Recruitment was through flyers newspapers and internet advertisements we telephone screened 566 people 83 in person 56 started the study 51 completed at least one session. And this just outlines the study design so this is a randomized double blind crossover design investigating both the acute and the sustained effects of a very low dose one milligram of psilocybin which is essentially placebo versus a moderately high dose of 22 milligrams per 70. The blinding conditions were designed to minimize expectancy bias and I won't go into those details but we put some considerable effort into not having these effects driven entirely by expectancy. Total participation time was approximately nine month to eight hour psilocybin sessions occurred about five weeks apart so after screening people were randomized to two groups. This group gets the high dose of psilocybin first five weeks later a low dose of psilocybin and they're followed up at six months. This just flips the order low dose first high dose and then follow up so there were no serious adverse events attributable to drug administration. Three of the participants died due to cancer related illness before the six month follow up this shows that within session time course of observer Raiders similar to what I showed you for the dose effect study. So again we're getting peak effects at two to three hours and tapering off the the low dose of psilocybin here is showing much greater effects than our placebo dose in in that other study. And this has to do with those expectancy controls people knew they are getting psilocybin they didn't know what dose they were going to get. They were told as were the guides you know go for it make everything you can out of this experience. So this shows mystical experience scores post session showing that the high dose expectantly produces much greater elevations and mystical experience. And this shows attribution of meaning spiritual significance and well being. So in the left hand panel here we're looking at a percentage of volunteers showing endorsing that this experience is in the top five most meaningful experiences of their lifetime. So this is five weeks after the low dose five weeks after the high dose here six months follow up after this high dose and you can see these effects are sustained. So there's a very specific effect of psilocybin and these effects are sustained. This is shown for spiritually significant and increased well being and life satisfaction. OK now what about our clinically relevant measure. So this is depressed mood is measured on the ham D scale. This is a gold standard clinician rated measure of depression. And the left hand panel here is showing clinically significant improvement which is defined as 50 percent reduction in symptom scores. This is five weeks after the low dose is 92 percent after the high dose. This is five weeks and this effects are sustained 79 percent at six months are continuing to show clinically significant improvement on depressed mood. Now this is showing remission to the normal range. So to get into this category scores on the ham D have to be seven or lower which is considered in normative range. So here you can see high dose. We have 60 percent remitting to normal range five weeks after this actually increases someone at six months. So virtually identical pattern of results are shown for the ham A. That's another clinician standard rating for assessment for anxiety now. And so we have 83 percent showing clinically significant improvement at six months. 63 percent have remitted into the normal range. This just says that in addition to the ham A and ham D we gave a variety of other measures assessing anxiety depression quality of life optimism and all these measures show the same kind of pattern of results. In addition we did community observer ratings of positive changes and those two showed sustained effects at six months. This now is showing this relationship once again between the post session mystical experience score and and outcome measures including personal meaning and the therapeutic efficacy. So the X axis here is showing total mystic mystical experience score. This is immediately post session. And these are follow up ratings at five weeks post session. And you can see there's a correlation once again and meaningfulness spiritual significant. But importantly on the therapeutic outcome measures anxiety and depression as well. So again there's something that's being captured by this scale post session this predictive now of therapeutic efficacy. And this is the cancer patients in in their own words. The seemingly big issue that take up so much of my mental real estate are insignificant. Even when I post the mental question about cancer it was irrelevant. There's another person deciding to go with life embrace life realizing that I had accepted death but I had not accepted life. I realized that I was glad to be alive. I've always thought I wouldn't be able to feel that a profound shift in the despair was not the truth that the part of me capable of finding the light remained. So as you might infer these these are very moving studies to conduct and the kinds of outcomes that we see are profoundly moving. And Alex Belzer will be presenting some qualitative research and a parallel study done at NYU describing at that at the more personal level what these kinds of changes were. So the conclusions here a single moderately high dose of psilocybin when administered under supportive conditions to carefully screen and prepared participants can indeed produce substantial and enduring like six months decreases in depressed mood and anxiety in cancer patients. Steve Ross and Jeff Gus Jeff is also here and will be presenting work from NYU have shown very similar effects in a recently completed study. The Hefter Research Institute and the Yosona Foundation have recently initiated communication with the FDA that's our food and drug administration in the United States trying to investigate the possibility of undertaking a phase three multi site clinical trial which is really the first step for regulatory approval of psilocybin as a medication. So let me turn now to psilocybin facilitation of addiction treatment so we can understand why psilocybin might have efficacy in in cancer patients who are psychologically distressed why would we think that it should have. Be a value in treatment of addictions well there are a couple lines of evidence anthropologically ceremonial hallucinogen use is associated with decreased addictions this is from the Native American church research from the 50s through 70s with LSD suggested decreases in alcoholism. The studies were mixed there's been a recent pilot study by Michael Bogan shoots though that seems to confirm that when we initiated these studies we were we were interested in looking at cigarette smoking because it's not encumbered by the medical and psychosocial degradations that we see with severe alcoholism or other forms of drug dependence and we we have conducted an internet survey and in that internet survey we identified 137 long term dependent smokers who reported complete and sustained abstinence from tobacco smoking that they attributed to a psychedelic experience. Interestingly they when comparing it to previous quit attempts they said there was less craving and the other curious pieces only 12% of this group had the intention to quit so this came on them spontaneously they had an experience and find themselves walking away from cigarette smoking. So that's the target that we sought to look at this was facilitation of smoking absence by psilocybin we used cognitive behavioral therapy for smoking cessation and we integrated that with our standard psilocybin preparation and support. We had up to three sessions the first of which was psilocybin corresponded to the target quit date and that was a moderate high dose of 20 milligrams per 70 kilogram and then there were two subsequent sessions one two weeks later one eight weeks later at a higher dose of psilocybin. 15 participants mean aged 51 10 male 5 female mean cigarettes per day 19 years of smoking 31 and previous quit attempts 6. In this shows the this shows urinary code mean across the study weeks this is median code mean level in the 15 volunteers so as they're acquiring the cognitive behavioral therapy they're not asked to quit smoking. You can see mean urinary code mean is is running high they hit the target quit date which corresponds to the first psilocybin session and boom medium levels are down to zero at six month follow up we have 80% abstinence rates which is really a remarkable number in the smoking cessation world. The best you can do with the very best treatment for renaissance is 30% or 35%. This shows this curious correlation once again between the mystical experience in this case predicting decreased smoking craving at six months so this is only 15 volunteers but again there's a regression there that suggests something's going on with that mystical experience or at least how it's reported at the end of the session so this work is proceeding now to randomized clinical trial. So the overall conclusions here is that with careful screening and preparation and when sessions are conducted in a comfortable and well supervised setting moderate and high doses of psilocybin can be administered safely. Under the conditions of these studies psilocybin occasion discrete experiences having marked similarities to classic mystical type experiences reported by religious figures throughout the ages. These experiences are associated with persisting positive changes in attitudes, moods and behavior. But an important implication is this the finding that psilocybin can occasion and most people study mystical type experiences virtually identical to those that occur spontaneously or naturally suggest that such experiences are biologically normal. And that now for the perhaps the first time this now these kinds of experiences column mystical transcendent whatever are amenable to systematic prospective scientific study. So we're turning to this slide there's so many different directions to take this work it's just remarkably exciting so we talked about some therapeutic applications and there's certainly others. But there are other other very interesting important questions to be asked in the behavioral sciences what behaviors are changed after such experience. What behavioral mechanisms account for such changes. In terms of biological psychiatry how to factors such as personality genetics, personal intentions, spiritual orientation affect the likelihood of these experience. And neuroscience what are the pharmacological and neural pathways and brain that are changed during and after such experiences. So I think with the progressive lifting of the restrictions on doing work with these compounds further research is surely going to reveal some of these underlying biological and behavioral mechanisms of action. And I would think it's really quite likely that it's also going to result in an array of therapeutic applications with various creative therapeutic targets. But what I think of as more importantly these mystical experiences or peak experiences transcendent experience whatever you want to call them appear foundational to our ethical and our moral understandings. They're really fundamental to this basic impulse that we have for mutual care taking and mutual respect. So further research with these substances then may ultimately prove to be crucial to the very survival of our species. Thank you. I think we have 10 minutes left for questions. So if you have a question please go to the microphone over there so you can make yourself heard. Do you collect any genetic information about the participants? And it's relevant to the others part. Do you do any research with race because African-Americans have different dispositions for different disease maybe also? Yes. Two good points. Sadly we have not collected genetic information. We have intended to call back a group of our volunteers and get that, do those screens because I think there are going to be a number of fascinating things to emerge. And the race question is certainly an interesting one. So our studies have been significantly over represented by Caucasians and we simply don't know. The use of, if you look at rates of use of recreational psychedelics those two tend to be highly biased toward Caucasian population. What's going on there? I don't know. Thank you very much for your very interesting and moving talk. My question has to do with age on which people have a mystical experience. It strikes me that the people in your research study have an age of about 44 you meant the average. But the mystical experiences that people have who use psilocybin on a recreational base is very often pretty young. And then I wonder if you have a sense of oneness but you are on the verge of becoming an independent person. You actually have to discover yourself. You have to learn how to support yourself in a materialistic world. Not only in such a world but also you need food, you need shelter and so on. Could you elaborate on the healthiness of a mystical experience related to the developmental stage in which somebody is? What an interesting question and it's not something that I've thought deeply about. It seems to me though that the answer has to come in terms of integration and support of these experiences. One of the keys that we're seeing in terms of making use of challenging experiences or mystical experiences is the meaning making that comes out of that. And so the context in which we're doing this work and some of our volunteers and some of our studies have been in the 20s. And they have had full on mystical experiences that they found incredibly valuable and they've integrated well into their lives. So it's that integration. Your point is taken in lack of some kind of integration of that experience. Even a mystical experience can be really quite disorienting in terms of life purpose. But it can be valuable for people on a subjective level. But if it results in that you're not able to find a house or to find a job because you think other things are more important. Is that a danger or not? No, I don't think that's a danger. If someone has a full mystical experience and has integrated it, the experience is actually to be more amashed with life, not less amashed. I mean these aren't people having mystical experiences and wanting to withdraw or go off to a cave and meditate. These are people who deeply appreciate the experience of being alive and in this world. And there's some meaning attached to that in terms of what they want to do with their lives. So they're going to solve their housing problems. We don't have people having these experiences and then end up on welfare. You remain optimistic. Maybe a little bit down to earth, not mystical. Did you rate, did you look at the sexual arousal aspects of psilocybin sessions? What the effect was on the sexual behavior of people afterwards? So we did not explicitly rate sexuality. I think we do have a question in our questionnaire about sexual feelings that arise during psilocybin sessions. I don't remember what the base rates of endorsement of those are, but they're pretty inconsequential. So I think there are some people who have energetic changes. Some people may experience that sexually, but it's not a high proportion and it's not a dominant theme. Besides those, what other effect, what other factors affect the likelihood of having a mystical type peak experience? I'm sorry, I missed the question, besides? Beside the dose, the dosage. What other factors, yeah. You know, we don't know, we don't know the answer to that. It's our impression, our people come in to be willing to participate in a study like this. One already has to be open and curious and interested in who they are and how they're going to be in the world. And I think, again, the context in which we're doing this is one of deep psychosocial support. So those are the domains that I would hypothesize might be important if you looked at the occurrence of mystical experience in the broader population during recreational use. But because we've narrowed our population and our setting conditions, we don't have very much information. As a matter of fact, one thing that I'll comment on is we actually have our guides rate what they think the probability is of people having a full transcendent experience. And our ability to predict that or to predict difficult experiences is pretty close to zero. So, but again, we have kind of a homogeneous population. Thank you. I think we have time for two, maybe three more questions before the break starts. I understand why you choose people with or prefer people without experience when you're doing the study. But then from the internet survey, you found that the people with the most challenging and rewarding experiences weren't, it wasn't during the first few times that they tried it. Is there some check on what the experience or how the experience changes experience? Let's see. We don't have sufficient data on that point. And I don't have an impression that with more experience, people are more likely or less likely to have mystical experiences. I'm sorry. This is the final question. I may have misunderstood, but was there a slide that said that the people who got the low psilocybin dose, like placebo almost, few of those rated it as the most important experience in their life? Yes. Yeah. So, so I, this is about seven setting and, and, and conditions. So we're running another study that I didn't describe in, in long term meditators, people who have decades of contemplative experience. And these people know that they can get assigned to placebo or active psilocybin. And a number of those volunteers and their hallucinogen naive, a number of those volunteers have come out of sessions that subsequently turned out to be placebo, convinced, convinced themselves and our guides that they got the active dose. They, you know, they're talking about the transcend. So this is, you know, this is, this is in our human biology. You know, you set the set and setting conditions right and, and these experiences can, can emerge. Thank you. All right. Please join me in thanking Roland for a great talk. Thank you very much.