Video: Psilocybin and Mystical Experience: Implications for Healthy Psychological Functioning, Spirituality, and Religion

September 29, 2020
Roland Griffiths presents Psilocybin and Mystical Experience
Roland Griffiths presented "Psilocybin and Mystical Experience" on Sept. 15, 2020.

Mystical-type experiences are profound and often characterized by an authoritative sense of the unity and sacredness and sometimes interpreted as an encounter with God or Ultimate Reality. Although such experiences have been described by mystics and religious figures throughout the ages, there are few experimental studies because such experiences usually occur at low rates and often unpredictably. Psilocybin in the form the Psilocybe genus of mushrooms has been used for centuries within some cultures for religious and healing purposes.

This presentation, held September 15, 2020, reviewed a series of studies investigating the effects of psilocybin administered to carefully screened and psychologically prepared volunteers who were encouraged to close their eyes and direct their attention inwards. Under such conditions, psilocybin occasions profound personally and spiritually meaningful mystical-type experiences in the majority of participants.

Roland Griffiths is Professor in the Departments of Psychiatry and Neurosciences and Director of the Center for Psychedelic and Consciousness Research at the Johns Hopkins University School of Medicine. His principal research focus is on the behavioral and subjective effects of mood-altering drugs.

 

FULL TRANSCRIPT:

[MUSIC PLAYING]

My name's Charles Stang. I'm the Director of the Center for the Study of World Religions at Harvard Divinity School. Welcome to our first public event of the year and our first fully online event. Thank you for registering in advance for this webinar. When we last checked, we had 477 people registered, attesting not only to the popularity of this topic, but also to this evening's speaker as well.

We have only an hour together, so I'm going to keep my remarks brief in hopes that there will be time for Q&A. I owe Ariella Ruth an immense debt of gratitude for all the amazing work she's done to prepare this seminar. So thank you, Ariella Ruth.

I'd also like to thank our co-sponsors, the Esalen Institute in Big Sur, California, who have just fought off the fires that are raging across the West. So thank you, and welcome, Esalen community. We hope for your continued safety and for your rebirth amidst so much ash. And thank you all in advance for your patience as we navigate this new online format for our events. We're not used to it, or at least I'm not used to it, and we hope it goes smoothly.

Tonight's lecture, by Roland Griffiths, Psilocybin and Mystical Experience, is the first in a yearlong series we're hosting here at the Center on psychedelics and the future of religion. I'll say more about that series in a moment. But please let me introduce our speaker, Roland Griffiths.

Roland Griffiths is professor in the departments of Psychiatry and Neurosciences and Director of the Center for Psychedelic and Consciousness Research at the Johns Hopkins University School of Medicine. His principal research focus is on the behavioral and subjective effects of mood altering drugs. He's a towering figure in what is often called the second wave of scientific research into psychedelics.

The first wave, of course, is very much entangled with the history of Harvard Divinity School and perhaps wasn't very scientific. I'm sure some of you here know this story better than I, and I've gotten conflicting reports.

But in April of 1962, a Divinity School doctoral student by the name of Walter Pahnke, under the supervision of his thesis advisors, Timothy Leary and Richard Alpert, allegedly administered psilocybin to 20 volunteers, including, I believe, Houston Smith, in a Good Friday service, in order to see whether and how it might occasion a, quote, unquote, "genuine" religious experience. I won't presume to tell you all what happened in the subsequent years, but suffice it to say that scientific research into psychedelics has come a long way since those early days, and much of that is due to the efforts of people like Roland Griffiths.

In his recent book, Michael Pollan describes Roland as, quote, "the last scientist one would ever imagine getting mixed up with psychedelics, which surely helps explain his success in returning psychedelic research to scientific respectability." Pollan says Roland is the ultimate straight arrow, at least until you get him talking about ultimate questions.

But I'm not so sure. This allegedly straight arrow has long harbored such questions about and experiences of the mystery of consciousness and existence, fed by a decades-long meditation practice. This evening, I suspect we'll see him weave in and out of those two sides of himself, the consummate scientist and the secret mystic, or so I hope. I for one am curious to see what winding path this arrow takes.

As I said, this is the first in a series we're hosting here at the Center on Psychedelics and the Future of Religion. If you're interested, please consider joining our events mailing list, so you're kept fully abreast. You can do so on the Center's website. The next event will take place on October 21, that's a Wednesday, from 4:00 to 5:30 PM, and is in many ways a follow-up to Roland's lecture.

It will be a panel discussion on medicalizing mysticism, religion in contemporary psychedelic trials. And it will feature two members of our own community who were subjects in those recent trials, one at Johns Hopkins, focusing on mental health, and one at NYU, focusing on religious professionals. The third panelist will be historian of religion, Jeff Kripal, from Rice University, who will help us make sense of all this from the perspective of the history of religion, mysticism, and paranormal or super normal experiences. So stay tuned. Much more to come in this series. In the meantime, please settle in and join me in welcoming Roland Griffiths.

Thank you very much, Charlie. Well, this is a great honor. So I'm going to speak to you for the next 15 minutes or so about psilocybin, mystical experience, the implication for healthy psychological functioning, spirituality, and religion.

I need to acknowledge a number of funding agencies that have supported this research over the years, including Fetzer Institute, Templeton, the Council on Spiritual Practices, Riverstyx, and a number of other groups and private sector supporters.

Our research has been done at Johns Hopkins. And what I'm going to focus in on is our work on psilocybin, although within the last year, we have now formed a Center for Psychedelic and Consciousness Research. And I'm joined in that Center by a number of very talented PhD and MD investigators, and we're moving ahead on a variety of fronts. Mostly focused on therapeutics, but we have this long abiding interest in implications for spirituality.

So just by way of background, psilocybin is a naturally occurring tryptamine alkaloid. It's the principal psychoactive component of the Psilocybe genus of mushrooms. And psilocybin in the form of those mushrooms have been used for hundreds, if not thousands of years, within various cultures, in structured manners, for religious, divinitory, healing purposes.

I'm going to just tell you a little bit about the historical use of psilocybin. And we can date that back. It goes back further, but it's clearly documented to 16th century Mexico, where the Spanish missionaries documented the ritualistic use of psilocybin mushrooms among the Aztecs.

And then missionary campaigns were set in motion against what was viewed as pagan idolatry, and they attempted to exterminate all aspects of this mushroom-centered religion, really destroying mushroom stones and other artifacts and forcing the mushroom ceremonies into secrecy, so much so that some people thought that this was-- that perhaps these religious never existed.

But in 1955, Gordon Wasson, a banker at the time, rediscovers indigenous use of psilocybin, ingests psilocybin mushrooms in Mexico, and publishes his account in Life Magazine in 1957. The very next year, Wasson having given the psilocybin mushrooms to Hoffman, and Hoffman is this chemist at Sandoz, in Basel, Switzerland, who had formerly, about 15 years earlier, discovered LSD.

Hoffman isolates psilocybin from the mushrooms. He publishes his synthesis the next year. And in that very next year, clinical research with psilocybin is begun, which is totally unheard of in this day and age, where the lag time from molecule discovery to clinical trials can be years and years, if not a decade or more.

1960 is a year quite relevant to this symposium. Timothy Leary and Richard Alpert at Harvard Psychology Department start a series of studies. And these studies are important because they recognize the powerful influence of set and setting as a significant determinant of psilocybin effects.

They conducted a subsequently discredited study, the Concord Prison experiment, claiming to show that psilocybin treatment reduced recidivism among prison inmates, but there was some creative use of statistics in that study, and it's been since discredited. It's an interesting study, nonetheless.

But as Charlie mentioned, in 1962, the Harvard Divinity School undertook a study. Well, it was Walter Pahnke, who at the time was a graduate student in theology at the Divinity School. And he conducted a study of psilocybin and gave psilocybin to graduate degree Divinity students in the context of a Good Friday service that was held in 1962, in the Boston University Marsh Chapel. So this is often referred to as the Good Friday Experiment or the Marsh Chapel Experiment.

Leary and Alpert were dismissed from Harvard in '63, and they were dismissed largely because of controversy about giving psilocybin to students and concern about the objectivity of their research. So that brings us to the 1960s and the drug excesses that came about during that decade, in combination with what I'll call the antics of Timothy Leary, who was a proponent for widespread use.

And it really completely undermined a scientific approach to studying these compounds. So much so that it led to regulatory and funding hurdles that functionally terminated scientific study with this whole class of compounds for decades. And human research really was largely dormant until the late 1990s, when a few laboratories in Europe renewed psilocybin research, and we at Johns Hopkins initiated our first trial.

Here's a descriptive definition of a classic psychedelic. So the classic psychedelic, sometimes called hallucinogens, and psychedelic is a word that was coined, meaning mind manifesting. These are a structurally diverse group of compounds.

That is they're different structures, but they all bind serotonin 2A receptors, through which they produce their principal site, that's their principle site of action. But uniquely, they produce this profile of changes in thoughts, perception, and emotions, often including profound alterations and perception of reality and meaning that are rarely experienced except in dreams, naturally occurring mystical experiences, and acute psychoses.

Just very briefly, risks and abuse of psilocybin. So psilocybin is classified as a schedule I compound. It has no recognized medical use. It's not considered to be a drug of addiction, because it doesn't produce compulsive drug seeking behavior.

Medical emergencies are very rare, but nonetheless, there's concern about potential adverse effects with psilocybin, and as well there should be. In principle, among these is panic reactions that can lead to dangerous behavior, including death and possible precipitation of enduring psychiatric conditions.

Just a brief comment on neuropharmacology, because time just won't allow me to take this on. But needless to say, this is a very active area of research, and substantial progress is being made in understanding drug and behavior mechanisms underlying these effects of these compounds. However, I would underline that the most interesting feature of psychedelics is that they produce profound, acute, and sometimes enduring alterations of consciousness.

And scientifically, we are, in fact, deeply ignorant about the very nature of consciousness. So this reflects the hard problem of consciousness. And the hard problem is the problem of explaining why any physical system is conscious rather than not conscious. And this strikes me as a mystical puzzle in and of itself. And I'll return to that.

So we initiated the development of our first study in 1999. And as Charlie alluded to, I had had no prior interest in psychedelics as a class of drugs. I was trained in behavioral pharmacology, having done a lot of work on drugs of abuse. About 25 years ago, I undertook a meditation practice which really opened up a whole host of questions for me about the nature of altered states of consciousness and spirituality and transformative experience and drew me into this area.

At this point, we have completed an ongoing studies in drug naive and experienced, healthy participants, novice and long-term meditators, religious professionals, clergy-- that I'm not at liberty to talk about, unfortunately, as appropriate as it would be to do this gathering-- depressed and/or anxious cancer patients, and then patients with major depressive disorder, addicted smokers, people with anorexia nervosa, and depressed patients with Alzheimer's. So to date, we have treated over 375 participants in over 700 psilocybin sessions. So we've accumulated a good bit of experience with these compounds.

What I want to talk about is the studies with healthy volunteers, because they are most germane to the question of spirituality and religion. So I'm going to summarize and blend together results from several different studies, but these are all rigorous, double-blind studies. Participants are medically and psychiatrically healthy. Most are without histories of psychedelic use.

So these are psychedelic-naive individuals for the most part. So we're looking at the effects of psychedelics in people who don't have strong a priori understandings or beliefs about this based on personal experience.

Participants met with session monitors on several occasions before the first session to develop rapport and trust, which we believe to minimize the risk of adverse reactions to psilocybin. And the conditions across these studies are designed to minimize expectancy bias, and we do this in various ways, and it differs across different studies. It could be placebo controlled. We go to some lengths to be as deceptive as we can be, ethically, in terms of not informing people about the precise study conditions. But they do indeed need to know at some point they're going to get psilocybin.

Our sessions are conducted in a comfortable, living room-like environment. And we ask the volunteer to come in in the morning, after having just a light breakfast. During the sessions, the volunteer is asked to lay on a couch. They're using eye shades and headphones through which they're listening to a program of music.

They're in the presence of two sitters or guides during the session who are there to provide reassurance should the volunteer need that. But the instruction, really, to the participant is this is an introverted experience, and you're to direct your attention inward, on your inner experiences. Not a guided session, per se. There's nothing to do other than to explore the very nature of the experience and whatever is manifest from that.

So this shows the time course of monitor ratings over the course of a six-hour period. And this is from a dose effect study. So here's placebo. Increasing doses of psilocybin. You can see that produces very-- and this is observer ratings, the guide ratings, of overall drug effects.

And so you can see there are very orderly dose and time-related effects here. Effects of psilocybin are coming on at 30 minutes, peaking at two to three hours, and then tapering off toward the end of the session. And by the time the volunteer's ready to go home, several hours later, they're back to normal baseline.

Well, as we might have imagined, psilocybin increases a variety of measures known to be sensitive to psychedelic drugs, based on research done much earlier. And these include perceptual changes, like visual illusions, greater emotionality, increased joy, peacefulness, less frequency of fear, anxiety. So people can become fearful or anxious despite the preparation and the holding that we do. And that's important to try to minimize, we believe.

And then there are cognitive changes, changes in sense of meaning, sometimes suspiciousness or paranoia. But what was most interesting and compelling to me when we first started this work was that in most volunteers, psilocybin produced large increases on self-rated questionnaires designed to measure naturally occurring mystical-type and insightful-type experiences. And what I should say is we, in effect, did a much more rigorous and controlled systematic replication of Walter Pahnke's Good Friday Experiment, showing that most of our volunteers showed these kinds of effects.

So this is showing post-session ratings of mystical-type experiences. This is a dose effect study. And this is immediately after sessions. And you can see it increases as a function of dose.

So what in the world is a mystical experience, and how does one go about measuring it? Well, these are the phenomenological dimensions of mystical experience that were derived initially by William James at the turn of the century and then by Stace in 1960. And Stace laid out these as descriptive features of the mystical experience.

The core features, this sense of unity, the interconnectedness of all people and things, all as one pure consciousness, this can be an introverted or extroverted type of unity. And that's accompanied by a sense of sacredness or reverence or preciousness for the experience. There's a noetic quality, a sense of encountering ultimate reality, that people feel these experiences are more real and more true than everyday waking consciousness.

There's deeply felt positive mood, sometimes the experience is universal love, joy, peace. Transcendence of time and space, where past and future collapse into the present moment. And the other component is these experiences are felt to be ineffable. One of the first things that people say at the end of the session is I can't possibly put that experience into words.

So we've done considerable work in refining the mystical experience questionnaire. And these are psychometric studies that are done in large groups of individuals. And what we ended up showing was the Stace factors, this first factor is unity, sacredness, and the noetic quality.

And that comes-- those cohere as a mystical factor. And then there are three additional factors. One was the positive mood, transcendence of time and space, and ineffability.

So here is a volunteer's written description of an experiment, of an experience. This was done either in the evening of the experience or the morning, but prior to meeting with the guides. And what I've done is highlighted the features that Stace calls out as being definitive of the experience.

So he says, "In my mind's eye, I felt myself instinctively taking on a posture of prayer in my head. I was on my knees, hands clasped in front of me, and I bowed to this force. I wasn't scared or threatened in any way.

It was more about reverence. I was showing my respect. I was humbled and honored to be in this presence. This presence was a feeling, not something I saw or heard, I only felt it. But it felt more real than any reality I've ever experienced.

And it was a familiar place too, one I had felt before. It was when I surrendered to this that I felt like I let go. I was gone, or should I say, this earthly part of me was. I was still on the couch, in some sort of suspended animation, awaiting my return.

I was in the void. This void had a strange and indescribable quality to it, that there was nothing to it but this feeling of unconditional and undying love. It felt like my soul was basking in the feeling of this space. I have no idea how long this lasted. Time and space did not exist there. It was all different manifestations of this love feeling I found myself wrapped in."

Mystical. So this may be less problematic for you, at the Divinity School, but I can tell you, in psychiatry and particularly in neuroscience, when I start talking about mystical experience, I get a lot of raised eyebrows. And so I need to explain to my colleagues that mystical experience in this case is defined by a respondent endorsing a constellation of empirically measured phenomenological dimensions, and the measure need not imply supernatural or non-rational levels of explanation.

So this is science, pure and simple, although my colleagues will sometimes be concerned that we're doing something that's [LAUGHS] illegitimate here, but it's not. And of course these experiences have been variously described over the ages, rapid conversion experiences. So James described these as conversion experiences or mystical, religious peak transcendental experience, transforming moment or epiphany.

And then turning to my skeptical psychiatric colleagues, who immediately said, well, your subjects are delirious, I had to take that head-on. And what we did is give them the Mini-Mental Status Exam, which is actually a gold standard measure of cognition. And it's used to assess delirium. And importantly, in this case, it's not affected at all across the same range of psilocybin doses that produce these full-on mystical experiences.

Another factor we think is important in the enduring positive effects that result from these experiences is psychological insight. And this is just showing post-session ratings of psychological insight.

So what I've described to you is the immediate effects of psilocybin and the kinds of reports that people are giving at the end of the session day. But the interesting piece of this is that well, of course psilocybin's a fairly short acting drug, so its effects are gone by the end of the day. But the very interesting piece of this is that the memories for these experiences endure, and people make remarkable attributions to them.

So here's a month after high-dose sessions. And we have about 80% of people saying that this experience is among the five most personally meaningful experiences of their lives. Another 80%, five most spiritually significant experiences of their life. When asked what this means, they'll say, well this is comparable in personal meaning to me as the birth of my first-born child or the death of a parent.

Respondents endorse large significant increases in positive changes in moods, attitudes about life and self, behavior, social effects, and spirituality. And they attribute these changes to the session experience. And then, remarkably, these effects are sustained through at least 14 months and in many, many cases, years later.

And they're also confirmed by ratings by friends, family members, and colleagues, work colleagues, that make of the participant's behavior. So this isn't just the participant's self-perceived changes. These changes are reflected by ratings done by we call them community observers. And we've shown that across a number of studies.

So this just provides a finer-grained sense of what people are endorsing. And this is positive attitudes about life. What's shown here graphically is that this is increasing as a function of dose, on the left, here. And here's what people are endorsing. They're endorsing increased life appreciation, gratitude, enthusiasm, meaning, richness, joy, optimism, dynamic quality, and positive life values.

This is the positive social effects that sometimes we call altruistic or pro-social. Again, dose-related increases. This is at six months in a different study. Increased positive relationships, tolerance toward others, love toward others, empathy, compassion, concern for vulnerable people.

And here's increased spirituality. And again, illustrated by increases in sense of reverence, a sense of the preciousness of life, the frequency of profound sacred experiences, the belief in some form of continuance after death, the sense that all life is interconnected, and an emotional bond with all of humanity.

So those are the kinds of ratings that are done. One of the remarkable things from a psychological point of view is that not only do people make these ratings on different items, that we're seeing changes in validated trait measures.

So traits are generally considered to be a relatively stable function of personality, and they're not changed readily. And I don't know of any situation in which-- any manipulation in which a single, discrete intervention changes trait measures. But here we have, in this study, these are six months changes in trait measures, showing this is psilocybin versus a placebo-like group. Increases in interpersonal closeness, forgiveness of transgression, gratitude, daily spiritual experience scale, the frequency of daily spiritual experiences, death transcendence, life meaning and purpose, mysticism, faith maturity index.

Now this slide actually makes a very important point and a robust point that I really want to underscore. And that is that the mystical-type experience assessed on the session day predicts positive outcomes on follow-up. And it does so after controlling for the intensity of the drug effects.

So let me just walk you through this. Whoops. What's shown here is this is essentially a mystical experience score right after psilocybin. And this is rating of spiritual significance a year later. And so if they're high on the mystical experience score after the session, they're high on spiritual significance a year later.

So there's something that's being captured in this mystical experience score that reflects positive outcomes later. And it's not just the intensity of the psilocybin experience. You could say, well, they just had more intense experiences. Well, no. Because if you look at the same correlation with the intensity, there's no meaningful correlation with spiritual significance.

So we've seen that and controlled that statistically in two studies in healthy volunteers and two different studies in cancer volunteers, and we've seen a correlation of that sort across a wide variety of other studies. So there's something fundamentally important to the nature of positive changes that occur, and it's being marked by these mystical experiences.

This is in their own words at 14 months. Volunteers were asked to reflect back on what was spiritually meaningful to you about that experience. The part that continues to stick out for me was the knowing, the seeing, the experience with every sense and fiber of my being that all things are connected. Here's another person. The sense that all is one. That I experienced the essence of the universe and the knowing that God asks nothing of us except to receive love.

Another. The feeling of no boundaries, where I didn't know where I ended and my surroundings began. Somehow I was able to comprehend what oneness is. And finally, the understanding that in the eyes of God, all people, abusers, abused, Christian fundamentalists, Muslim fundamentalists, atheists, we're all equally important and equally loved by God, and that given the proper circumstances, I could be any one of them.

We've also conducted a study in long-term meditators. We did this because there's been almost no research of psychedelics and long-term meditators. We are interested in whether they experienced beneficial or potentially harmful effects.

We think that meditation and psychedelics can be viewed as complementary techniques for exploration of the nature of mind and self. And there are neuroimaging studies that show meditation and psilocybin produce strikingly similar changes in brain circuits responsible for self-referential processing.

So in this study, it was a randomized placebo-controlled design. 40 participants with substantial meditation experience, about 6,000 mean hours of meditation for each person, 17 mean meditation retreat experiences, little or no past use of psychedelics. The study involved one to three sessions, and during some of the sessions, participants engaged in several short periods of meditation.

And I just have some very preliminary data to share with you. We're doing more detailed analyses now. This shows results from the mystical experience questionnaire done immediately post-session in the group that received-- this is a moderately high dose of psilocybin versus placebo. So not surprisingly, we're seeing increases in mystical experience, much greater in the psilocybin group than the placebo group.

But this is two months later. And these are the attributions that people are making to these experiences. These are long-term meditators. And you can see with the pink, compared to the blue, that they're endorsing at much higher rates that the experience was among the top most spiritually significant of their lives, the most personally meaningful of their lives, and that it increased life satisfaction.

And this shows their claims about the impact on their spiritual practices. So here we're showing increases with psilocybin on positive effects on non-sitting awareness practices, greater flexibility in how they hold their meditation practice, and positive effects on their sitting meditation practice.

So overall, we conclude here that despite decades of contemplative practice, psilocybin produces personally valued experiences along positive effects on meditation and daily awareness practices. But I would underscore that although these experiences are valued, no one would claim that the psilocybin is a substitute for meditation, which results in much greater stability into day-to-day awareness practice.

We've done a wide range of anonymous survey studies, and there's only one of which I'm going to talk about. But this has been a very fruitful avenue to gain information about mystical-type experiences, adverse experiences. We have one on near-death experiences.

But what I want to talk about is God encounter experiences. So in this study, this is an anonymous internet survey. Survey respondents endorsed having had an experience of encountering something that someone might call God, e.g. God of your understanding, higher power, ultimate reality, or an aspect or emissary of God, e.g. an angel.

And we targeted two populations, two groups. Those who had such an experience after consuming psilocybin mushrooms, this is the psilocybin group, and those who had such an experience in absence of taking a psychoactive drug, the non-drug group. And so this shows some demographics from these groups.

You can see we acquired a good sample size here, about 1,100 people with psilocybin, about 800 in the non-drug group. And they're very divergent populations demographically. So the non-drug group-- and it's probably not surprising-- the non-drug group tends to be older, more female, more educated, and a higher income.

Yet their intention for having an encounter experience was low in both cases and really not different. But what was different is the descriptor that they used to describe that which was encountered. So they were given a choice. Well, you said you encountered God or ultimate reality, higher power. Which of these is the best descriptor?

And so in this case, you can see the orange shows the non-drug group. The non-drug group was more than twice as likely to endorse that they had encountered something that they feel most comfortable describing as God or an emissary of God, where in contrast, the psilocybin group was more likely to say they encountered ultimate reality. And both groups endorsed higher power.

So they're very different demographically. They're very different in terms of their descriptor. But now we ask them this. They say, well, what are the attributes of that that you encountered?

So independently, whether you call it God or ultimate reality, tell us the qualities of that that you encountered. And here-- and I think it's fascinating and remarkable-- the groups look very much the same. So what you can see at high rates being endorsed is whether or not they call this God or ultimate reality, what they encountered was intelligent, sacred, benevolent, eternal, and conscious. And it was not malicious or negatively judgmental.

The memory for the encounter experience was very similar across the two groups. This is the experience being more real than everyday reality. Here's the mystical experience questionnaire. And again, very, very high scores in both groups. So the non-drug group was no doubt experiencing something quite similar to the psilocybin group, as at least measured by the mystical experience questionnaire.

And here's the attributions to the experience. So what was the value of this experience to you. How do you rate this in retrospect. And you can see, they're very similar. And this is ratings of the top five most experiences. So they're highly spiritually significant, personally meaningful, and psychologically insightful, with some differences. Some of those differences may be significant, but you can see that they're much more similar than different.

Atheists. So one of the interesting questions here was among those who identified as atheists before the encounter. And perhaps not surprisingly, the rate of identification of atheists was much higher in the psilocybin group than in the non-drug group. However, after the encounter, the majority of these atheists in both groups no longer identified as atheist. So 57% and 67%, respectively.

So that suggests that these experiences were conversion experiences for the majority of atheists who participated. And that doesn't mean that they became believers, but it does mean that they were no longer willing to identify as atheists.

Conclusions. Overall, these data suggest psilocybin-occasioned experiences of the divine may represent a model system for understanding non-drug, naturally occurring experiences most often described as a personal encounter with God.

Therapeutic applications. Well, time won't permit me to go into any detail other than to tell you that this research is looking very promising. And we've done studies of depression, anxiety, exacerbated by life-threatening cancer diagnosis. We've looked at major depression. In fact, we have a significant publication coming out next month. And we've looked at cigarette smoking.

Just to illustrate this, here is the effects of psilocybin on depressed mood in cancer patients. Now, the measure that we're using here is something called the HAM-D, the Hamilton Depression Inventory. It's a gold standard measure for assessing depression. It's given by a clinician.

And this is showing clinically significant improvement. You have to have a 50% drop in HAM-D scores. And you can see, five weeks after the high dose, you have 92% showing significant clinical improvement, much higher than after the low dose.

And if you look at remission, so remission to normal range means these individuals no longer look any different from the normal population. You have 60% fully remitted at five weeks. And if you go out to six months, you can see these effects are sustained. So that's really quite remarkable, a single dose of psilocybin producing these huge changes. And they endure.

And this shows psilocybin-facilitated cigarette smoking cessation. A study done by Matt Johnson in our group. This was an open label trial, where we're doing controlled comparative efficacy trials now. But the bottom line here is you take a group of long-term smokers who have failed multiple quit attempts.

And this is urinary cotinine, which is a measure of nicotine in their urine. And they're given cognitive behavioral therapy. Psilocybin corresponds with their quit date. And boom, we're dropping this median urinary cotinine down to zero across this period, with 80% abstinent at six months, which is just unheard of in the cigarette smoking literature.

So these clinical trials are moving apace. I think it's likely that we'll see approval of psilocybin for the first indication, which would probably be depression or treatment-resistant depression, in the next four to six years. But there are a number of very promising clinical applications.

So how does this stuff work? Well, we don't really know. But as I've mentioned, mystical experience appears to be a key factor and a correlate or a predictor of positive outcomes. Related, perhaps, to that is just the ontological shock that occurs in some of these experiences that result in a profound shift of sense of self and worldview that may result in a reconstruction of life story and a loosening of self-focused narrative and resulting in increased psychological flexibility. And then, as I mentioned, insight about self or relationships, which may be experienced as memory or catharsis.

This is a working model we have showing that acute mystical experiences, this is done from survey data with large groups of people. And this is a path, a statistical path model of analysis. But acute mystical experience and insightful experience feed into this measure of psychological flexibility that then highly predicts decreases in depression and anxiety among people with depression and anxiety. And so we think that's at least a psychological model that's apt here.

So in conclusion, under the conditions of these studies, psilocybin-occasioned discrete experiences, having marked similarities to classic mystical and insightful experiences. These experiences are associated with enduring positive trait changes in attitudes, moods, and behavior.

The finding that psilocybin can occasion, in most people studied, mystical and insightful experiences virtually identical to those that occur naturally suggests that such experiences are biologically normal, and that such experiences are now amenable to systematic, prospective, scientific study. So heretofore, the mystical experience was rather a puzzle. And because we didn't have conditions under which it could be produced reliably, we really couldn't study it.

But now, indeed, we can. And the opportunities for research in this area are enormous. And so sometimes I feel like a kid in a candy shop as a basic scientist. Because there are so many potentially really interesting questions to be addressed.

So biological psychiatry, how do factors such as personality, genetics, personal intention, affect the likelihood of such an experience. Neuroscience, what structural and functional changes in the brain account for these experiences. What behaviors are changed after such experiences. Are there therapeutic benefits. And we suspect transdiagnostic applicability to not only depression, but drug dependence disorders, eating disorders, PTSD, et cetera.

But more to this audience, what about altruism and prosocial behavior? What are the implications of these findings for studying and promoting altruism and ethical behavior? And what about spirituality and religion? What are the similarities and differences between psychedelic occasion and naturally occurring spiritual or religious experiences.

How are such experiences interpreted by those who are committed to different faith traditions? What are the implications for promoting spirituality? The last, broadest, and to me, the most fascinating implication, again reflects back to what I previously mentioned, the finding that psilocybin can occasion, in most people studied, these mystical-type experiences, virtually identical to those that occur naturally.

So the question arises, why? Why are we disposed to have such compelling, felt to be sacred experiences of ultimate reality and the interconnectedness of all people and things. Experiences that arguably provide the very basis of our ethical and our moral codes that are common to most of the world's religions.

I think there's something about the mystical experience, and this reflects back on the puzzle of it, that relates intimately to the very nature of consciousness itself. Reflect on the mysterious truth that if you turn your attention inward, you can become aware that you're aware. Become aware that you're aware.

And when you do, an indisputable and profound inner knowing arises that we can access individually and perhaps collectively. It's really at the core of our humanity, isn't it? We recognize that we're all in this together. And there's this impulse for mutual caretaking that arises. I believe that exploration of this inner knowing through contemplative and other spiritual practices can result in profound uplifting shifts in worldview, a waking up to a sense of freedom, peace, and joy, gratitude, that many people simply find unimaginable.

Excitingly, psilocybin occasioned mystical experiences appeared to provide a model system for prospective and rigorous investigation of these awakening experiences. Further research will surely reveal underlying biological mechanisms of action and will likely result in an array of novel therapeutic applications. But more importantly, because such experiences appear to be foundational to our ethical and our moral understandings and this mutual caretaking, further research may ultimately prove to be crucial to the very survival of our species. Thank you.

Thank you, Roland. I suspect that some people will want to see some slides again, so you may want to keep your screen share as it is.

OK.

We have five minutes left. I've been monitoring the Q&A, and I have two questions that are actually kind of cobbled together from a number of questions that I've received. So the first is actually close to my own heart, and that is about the category of mystical experience. Not surprising that I would ask this question, I'm a historian of mysticism.

And what struck me about your presentation is that the list of qualities of experiences deemed mystical derived from William James and Stace doesn't exactly correspond to the archive of mystical literature. And let me give you two sets of experiences that I think seem kind of missing. And I don't know if they're in fact missing from these people's experiences, or whether they've been filtered out for any reason.

So here's two general categories of experience that are familiar to me from the archives, so to speak. What is profound experiences of divine darkness, which can be harrowing, challenging, compunctive, even fearful. Not menacing, necessarily, but overwhelming and overpowering. Even the idea that the divine might abandon you.

So abandonment is an enormous concern in mystical archives. But let's just say generally experiences of divine darkness. Where do those come?

The second general category which I didn't see is the deeply personal encounter people have with other entities in mystical archives. So in a Christian idiom, this is usually found as-- these are usually experiences of Christ, obviously, but also saints, angels, other mediating figures between you and the source.

Now, some of you might say, well, those don't qualify as fully mystical, because they are not experience of the source, the godhead itself. But they are often thought of as part of the choreography or the landscape of one's approach to the godhead. So I'm wondering, I suppose, I'm wrestling with this disparity between the experiences you've collected and studied and the archive I'm more familiar with.

And I'm wondering, is this because these-- are these experiences coming up for your-- for the people you're studying, and are they being filtered out, either through the questionnaire or through some other filter that you're applying to it as perhaps adverse reactions that we don't need to attend to, or are they just fully absent, in which case, I think we need to wrestle with why there's such a disparity between this very modern archive and then the centuries-long archive.

Yes. What a great question. No, those qualities are not missing at all in these experiences. So our framing of the mystical experience questionnaire took off on Stace's descriptive categories. And so Stace does not-- didn't consider entity contact to be a descriptive feature.

But nonetheless, like the study that we did, the survey study of encounters with God, God of your understanding or emissaries of, these kinds of attributions of entity encounter experiences are actually quite common. And we've just completed a different survey-- I didn't talk about it-- about DMT entity encounters, which are very peculiar, but they have a lot of the same features of the God encounter experiences.

But so we capture some of that, but we haven't captured that systematically. And it's not part of the mystical experience questionnaire. Because the mystical experience questionnaire is tending to capture the light side of things. And of course there are these very dark experiences. And they're kind of the classic challenging experience that come into play with psychedelics.

And it may be the experience of the existential vacuum, of the void. And that can be absolutely terrifying. But there's no question that that comes up. And we have an entirely different questionnaire, something called the challenging experience questionnaire. And we try to tap into that. We've been very interested in that feature. But I think psychometrically, it falls apart from at least what we're describing as the classic mystical experience that's positively balanced.

Yes. I suppose what I'm-- I suppose what I'm arguing is that that allegedly classic mystical experience is actually not in his dialogue with the classics of mystical literature in some sense. But let me pivot to a second question. And I know it's 6 o'clock, so if anyone needs to depart, I'm sorry that we ran over. But this is drawn together from a number of comments that I've read. And this will be the last question.

Someone was-- I'll bring up the image of the single person on the couch, lying down, with the headphones and the blindfold. That really underscores that these are deeply individual experiences. Now, was there any consideration of studying group sessions? Because this is of course how psychedelics have been experienced in other contexts around the world and even in the, so to speak, psychedelic underground.

And I think about this because often people will report-- well, people will do psychedelics in community, together with friends. And then they go on a trip. There's a journey. There's a shared quality to the experience.

And I wonder what happens to that dimension of psychedelics and its implication for spirituality and religion when we essentially insist that the subjects are in a kind of sensory deprivation. Well, or not so much sensory deprivation, but it's a very highly curated sensory experience. And in any case, it's not in community. And I suppose one of the worries here is that this seems to reflect the culture's kind of insistence on the individual, the kind of atomized subject. So I'm wondering if you could reflect on that.

Yes. So as you know, Stace actually pointed out the differences between introvertive and extrovertive experiences. So not only do you not have community, our situation is engineered to focus on the introverted experience. You could put someone out in a nature setting alone or in a group and have a very different kind of experience.

The answer to how we have got here right now just follows from the kind of basic scientific principles. It's much easier to do research and get valid results in individual subjects. Because as soon as you bring groups together, the complexity of monitoring a group goes up astronomically.

But also your ability to draw inferences about experimental manipulations is degraded enormously. Because statistically, you need to treat the group as a single individual. So that was one of the problems with Walter Pahnke's Good Friday Experiment.

You know, he gave the drug to everyone all at once, and they were all in the same room together. And so you get this confounding where people are playing off of each other's experiences. It's an interesting thing to do, but in terms of scientific tractability, it doesn't lend itself there.

I mean, what this really underscores though is how little we understand about this and how much more there is to do. And certainly the issue of community is hugely interesting and important and relevant to understanding the principles that are just germane to religious practice worldwide.

It sort of reminds me of Newtonian physics, which strips out certain kinds of context, so you can teach someone how objects interact in this sort of abstracted sense, but there's a way in which that doesn't actually fully reflect how objects in the world interact. So I suppose that the provocation I'm aiming for here is whether this fact, that there are certain aspects of psychedelic experience that do lend themselves to scientific inquiry, but may point out the limits of that, suggesting that there are aspects of psychedelic experience that are simply very difficult for science to approach, such as this group dynamic and--

Well, but-- yeah, no. Let me just come back. No, we could address that, but it's a question of cost and effort. So to do those studies and to do them well, the budgets for that would be 10x. And these studies as they sit are enormously expensive, at least as they have been laid out and approved within tightly controlled medical institutions. As we develop more familiarity with them and have a better understanding of their safety profile, then group experiences of that sort will lend themselves to scientific study.

OK. Roland, we've kept you past the hour. And I just want to say thank you so much for your time, for this fascinating lecture. And I, for one, have many more questions, as I'm sure the 44 Q&As that I'm looking at also do. It's a testament to the richness of this lecture. So...

Thank you, Charlie.

And for those of you who are still with us, please join us October 21 for the follow-up. We'll still very much be talking in the wake of Roland's presentation and asking questions about these trials. OK. Until then, be well. And thank you all for registering and tuning in.

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