[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