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  • [Johns Hopkins Psilocybin Research Project:]

  • [Studies of Mystical Experience and Meditation]

  • [in Healthy Volunteers, and Palliative Effects]

  • [in Cancer Patients]

  • [Roland R. Griffiths, PhD April 21, 2013]

  • Well, thank you very much for being here. I woke up this morning

  • feeling really gratitude-filled, not only for the opportunity

  • to participate in this research, but to the organizers of this meeting:

  • MAPS and Beckley Foundation, the Heffter Research Institute,

  • the Council on Spiritual Practice, and particularly Rick Doblin,

  • who did just a terrific job in pulling this together. And gratitude

  • also to the larger community that comes together. So what I want

  • to do today is talk about our program at Johns Hopkins

  • looking at mystical experience in healthy volunteers. This is our

  • psilocybin research project. And just start by commenting

  • that support for this has been provided by grants from various

  • different entities, including the Heffter Research Institute,

  • Council on Spiritual Practices, the Beckley Foundation,

  • the Riverstyx Foundation, Betsy Gordon Foundation,

  • the Cormac family and the National Institute on Drug Abuse.

  • Our research is being conducted

  • at the Bayview campus of Johns Hopkins School of Medicine,

  • and I also want to underscore that I'm just a figurehead

  • up here for a very dedicated and competent research team.

  • There are actually ten of us here at the meeting today, nine

  • of whom have given presentations already, and we have, I think,

  • six others from the team, not all full-time, back in Baltimore.

  • But in addition to me there's Bill Richards who's been our

  • chief clinical mentor, and he gave a spectacular talk yesterday

  • reflecting on his 25 years of experience of doing research with

  • psychedelic drugs; Matt Johnson, who's been with us since 2004

  • and who's my kind of scientific alter ego at Hopkins, he's been

  • very involved in all of the psilocybin research throughout

  • the time that we've been doing it; Katherine MacLean, who's

  • joined us recently, and joined the faculty, comes with a particular

  • interest in meditation, which is a focus of some of our research

  • and of interest to me; Mary Casamano and Brian Richards,

  • who spoke yesterday about managing difficult experiences;

  • Mary probably has the distinction of being someone who's guided

  • more approved psychedelic sessions than any other individual

  • in the last couple decades: hundreds of sessions;

  • and then Al Garcia-Romeu and Matt Bradstreet are post-docs.

  • Al's been working on the psilocybin smoking cessation project.

  • Matt has just headed up an interesting survey study on challenging

  • experiences. He presented a poster, and Al talked about his work,

  • I think, on Friday. Maggie Kleindienst keeps our unit together.

  • She's our liaison to FDA, DEA, our IRB, and she manages

  • and coordinates all of our studies. Bob Jesse, who has been

  • involved from the inception of this work with healthy volunteers

  • and the interest in mystical experience. So we initiated

  • the development of our first study back in 1999, so it's been a while,

  • and initially recruitment and the studies proceeded really

  • quite slowly, partly because of funding, partly because of logistics.

  • But we've completed two very major studies, one in healthy volunteers

  • and a survey study, and we've spun off at least seven publications

  • at this time, but things are picking up. So there's a number of

  • ongoing studies, some of which I'll mention today: effects of

  • psilocybin in beginning meditators. We're just initiating study of

  • psilocybin effects in long-term meditators. Psilocybin treatment in

  • psychologically distressed cancer patients: that's a study that's

  • ongoing, and I'm choosing not to talk about it because Charlie Grob

  • and Steve Ross and Tony [Bossis] have all talked about their trials,

  • but I do want to put in a plug, that we're actively recruiting.

  • We need another 15 volunteers. We have a travel grant program,

  • so we can bring people in nationally, and so if you know of anyone

  • who has some existential distress around the cancer diagnosis,

  • please let them know of our study. The website is cancer-insight.org,

  • and if they go to that website there's plenty of information

  • about the study and how to enroll. Finally, the final ongoing study

  • that Matt Johnson'll be talking about later this afternoon

  • is a pilot study of psilocybin facilitation of smoking cessation,

  • which is a really fascinating study with very interesting results.

  • So to date, we've run 190 volunteers over 460 sessions.

  • So we've gained pretty substantial experience with these compounds,

  • and this is all moderate to high dose, 20-30mg/70kg, so these are

  • high-dose sessions. Briefly, by way of background, psilocybin

  • is a naturally occurring tryptamine alkaloid. It's the principal

  • psychoactive component in the Psilocybe genus of mushroom.

  • Mushrooms have been used for thousands of years within in various

  • cultures in structured or divinatory settings. So there's this long

  • historical use, medical and sacred use of these compounds.

  • The classic hallucinogens, this is our best working definition

  • of it. The classical hallucinogens are a structurally diverse group

  • of compounds, bind 5HT(2A) serotonin receptors, and produce

  • a unique profile of changes in thought and perception and emotions,

  • often including profound alterations in the perception of reality,

  • that are rarely experienced except in dreams, naturally-occurring

  • mystical experiences, and acute psychoses.

  • So psilocybin is a tryptamine and DMT is also a tryptamine.

  • There's a phenethylamine serotinergic or classic hallucinogens

  • such as mescaline and DMT. One other comment about background:

  • considerable research was conducted with psilocybin and the

  • classic hallucinogens back in the '50s and '60s, and as we all know,

  • subsequently, research for these compounds went dormant for

  • two or three decades, depending on what laboratories were working.

  • But the substantial work was shut down for close to four decades,

  • and it was in response to the widespread medical use and concern

  • about potential harms, and in my opinion the antics of Timothy Leary,

  • which really undermined a scientific approach to studying

  • these compounds. But we had a cultural trauma surrounding

  • research with these compounds that's really unprecedented,

  • as far as I'm concerned, in science generally. So this is an overview

  • of what I want to talk to you about this morning. I'm going to

  • describe our two published studies in healthy volunteers

  • characterizing mystical experiences, go on to two ongoing

  • studies in meditators, one in novice meditators and one we're

  • just about to undertake in long-term meditators, and then I'll

  • talk about two web-based anonymous surveys in which we've

  • been looking at the effects of psilocybin when people ingest

  • mushrooms in non-research settings, and very briefly with some

  • conclusions, implications, and future directions. So the two published

  • studies in healthy participants: both studies used double-blind

  • crossover designs. The first study, 36 participants, two or three

  • sessions at two-month intervals compared a high dose of psilocybin

  • with a high dose of methylphenidate or Ritalin. The design effectively

  • obscured to volunteers and monitors exactly what drugs were

  • being tested. The second study: 18 participants, five sessions

  • at one-month intervals, comparing placebo, 5, 10, 20, 30 milligrams

  • of psilocybin administered in mixed sequence across sessions.

  • Actually, it was mixed but half got ascending, half got descending with

  • intermixed placebo so they didn't know that.

  • The participants in these studies were recruited from the local

  • community through flyers and newspaper advertisements.

  • The study participants were medically and psychiatrically

  • healthy, without histories of hallucinogen use. We did this

  • intentionally to reduce the possibility that we'd have selection bias,

  • that people didn't differentially come into the study who had had

  • good effects with psilocybin and then confound what kind of

  • generalities we could draw from that. The volunteers didn't receive

  • monetary compensation for participation.

  • So, the participants: just one comment. I'm going to intermix the

  • description of the methods and results for these first two studies,

  • because they're really so similar, so what I'm doing here now is

  • providing demographics for both of the studies combined

  • rather than try to parse those apart. So the mean age of these

  • 54 volunteers in these 2 studies was 46 years, half female,

  • highly educated, most employed full-time, part-time. We had

  • physicians, psychologists, counselors, pastoral counselors,

  • business owners, consultants, a wide variety primarily of

  • professional-level people. In terms of religious, spiritual

  • activities, all 54 indicated at least intermittent participation

  • in religious or spiritual activities, such as religious services,

  • prayer, meditation, church choir. We did this partly because it's

  • consistent with the long historical use of these compounds

  • sacramentally, and also to reduce what we thought might be

  • some inherent variability. So volunteers...our basic way that we

  • approached these studies is very similar to that's already been described

  • by these other research teams. Our volunteers meet with monitors

  • for up to 8 hours of contact time prior to the first session,

  • and the purpose of this is to establish good rapport, and trust,

  • because the thought is that that's going to minimize adverse effects

  • to psilocybin. Studies are conducted in aesthetic living-room-like

  • environment. This is a laboratory's unlike any other that we have

  • in our psychopharmacology research unit. This over-showed slide

  • at this juncture, I think it's been showed ten times over the course of

  • this meeting, shows what happens on session days. So people come in

  • at 8 in the morning, they take a capsule, they're in the presence

  • of two guides or monitors throughout the day. They're asked to

  • lay on the couch, wear eyeshades and headphones through which

  • they listen to a program of music. The guides are there to provide

  • reassurance if anxiety or fear come up. That could just be

  • verbal reassurance or touch to the shoulder or holding a hand.

  • But it's our intention to let people have their own experience,

  • and we ask them to go inward. So this isn't guided in any psycholytic

  • kind of sense of how some of these sessions have been

  • conducted in the past at lower doses, because we're interested

  • in these high-dose sessions. So this shows time course of

  • monitor ratings. This is from the dose effects study. Just showing

  • the very orderly time- and dose-dependent effects of psilocybin.

  • Onset's occurring 30 to 60 minutes, peaking at 2-3 hours, and

  • decreasing toward baseline. Even 5 milligrams under this condition

  • is really quite active, which surprised us. Self-reported

  • effects of psilocybin: it wasn't surprising to us, and I'm sure

  • not to you, that psilocybin increased measures previously

  • shown to be sensitive to hallucinogen drugs. So there are perceptual

  • changes such as visual illusions, greater emotionality, such as

  • increased joy, peacefulness, sometimes fear and anxiety--

  • I'll come back to that--and cognitive changes such as sense of meaning,

  • sometimes some paranoia. But we think that at least for me, for sure,

  • the most interesting effect that we had was that in most volunteer

  • studies psilocybin produced these large increases in these

  • self-rated questionnaires designed to measure naturally occurring

  • mystical experiences. This shows the results of the dose effect study

  • on the Hood Mysticism Scale and the Pahnke-Richards

  • Mystical Experience Questionnaire, just showing clear dose-related

  • increases. This is interesting. The Hood Scale was developed

  • based on naturally-occurring mystical experiences, using

  • criteria developed by [Stace] in 1960, and it had never before

  • been used in any sort of drug study. We're getting robust increases

  • and it's those kinds of observations that make us feel quite

  • confident that this is an experience that really maps on to

  • naturally occurring mystical experiences. This just shows the

  • percentage of volunteers who fulfilled criteria for having

  • a so-called "complete" mystical experience, and I'll tell you

  • what that is in a second, but we get nice dose-related increases

  • in that with about 75% of volunteers fulfilling this criteria

  • at either the 20 and/or the 30mg/70kg dose. So the 75% of people

  • are meeting this criteria for having a complete mystical experience.

  • These are the phenomenological dimensions of mystical experience.

  • Again, this been covered in other talks. The core feature is

  • this sense of a unity, this interconnectedness of all people

  • and things, the sense that all is one, everything's interconnected.

  • This is accompanied by a sense of sacredness or reverence,

  • a noetic quality of encountering ultimate reality, that this is

  • more real and more true than everyday waking consciousness,

  • a deeply felt positive mood, sometimes described as universal

  • love, joy, peace, gratitude. Transcendence of time and space,

  • past and present collapsed into the present moment. That becomes

  • all there is. Space is vast, endless, the void, perhaps.

  • These experiences are described as being ineffable with people

  • who have had them. They're not simply put into words.

  • So those are the dimensions of the mystical experience.

  • The interesting piece of our work, fascinating to me, when we

  • initially started this work, was that the kinds of attributions

  • that are made to the experience really persist. So this is a questionnaire

  • given two months after sessions. We're asking people how personally

  • meaningful and spiritually significant...no, how personally

  • meaningful was this experience on a scale from an everyday

  • experience, once a week, once a year, up to top 10, top 5,

  • single most meaningful experience of my life. The fill bars are

  • psilocybin, striped bars are methylphenidate. So you can see this

  • remarkable effect where about 70% of people are saying this

  • experience that occurred over an 8-hour session in a Johns Hopkins

  • pharmacology laboratory is among the five most meaningful

  • experiences of their lives. It seemed so improbable to me when we

  • started this, and they would compare this to the birth of their first-born

  • child or the death of a parent. So they're really remarkable,

  • salient experiences. This is an equivalent questionnaire.

  • How spiritually significant was this experience? Thirty percent

  • of these people who were already spiritually inclined are saying

  • it's the single most spiritually significant experience of their lives

  • and again, about 70% are saying it's in the top five.

  • This shows similar data from the dose-effect study. This is percent

  • of volunteers rating the experience in the top five spiritually

  • significant of their lives. You can see we just get nice dose-related

  • increases, going up to 83% at the highest dose. This is single most

  • spiritually significant experience of their life, and here we're getting

  • 45% of these people after the 30mg/70kg saying it's the single

  • most spiritually significant experience of their life.

  • This shows effects that people talked about, again, two months

  • after sessions, when we asked them to complete a questionnaire