The following is a conversation with Rick Doblin, founder and executive director of the Multidisciplinary

Association for Psychedelic Studies, MAPS.

He is one of the seminal figures in both the cultural history and the cutting edge science

of psychedelics.

He was there, along with the biggest characters, throughout this fascinating history of psychedelics,

and he is here to tell the story.

Quick mention of our sponsors, TheraGun, ExpressVPN, Blinkist, and A.Sleep.

Check them out in the description to support this podcast.

As a side note, let me say that exploring the places the human mind can go can help

us understand where it comes from, how it works, and how to engineer mental journeys,

whether that's through life experiences, chemical substances, brain computer interfaces,

or interactions with artificial intelligence systems.

On a personal level, I think the dissolution of the ego for stretches of time is a powerful

tool for understanding yourself.

A lot of things can do this, including jiu jitsu, literature, meditation, but psychedelics

is definitely, or at least arguably, one of the most powerful, from psilocybin to DMT.

I'm excited that people like Rick are leading the scientific research that reveals the efficacy

and the safety of these substances, so that their proper dosage and usage protocols can

be understood, and people like me can safely and effectively use them, not just for recreation,

but for rigorous exploration of my own mind.

This is the Lex Friedman podcast, and here is my conversation with Rick Doblin.

Could you give an introduction to psychedelics, like a big, bold, whirlwind overview?

What are psychedelics?

What are the kinds of psychedelics out there in whatever way you think is meaningful?

All right.

When I started MAAPS, the Multidisciplinary Association for Psychedelic Studies, it was

very important for me that psychedelic be in the name, and the way in which the original

meaning of psychedelic is mind manifesting.

It was created by Humphrey Osmond in dialogue with Alotus Huxley.

Psychedelic means mind manifesting, and so we interpret that very broadly to mean dreams

or psychedelic.

Anything that brings things to the surface, the holotropic breathwork, hyperventilation

is psychedelic.

Most people think psychedelic is only about certain chemical substances, either natural

or synthetic, but we've got a much broader view of that.

Meditation can be psychedelic in some ways, but our primary focus is on the drugs, is

on the medicines, or some people might call them spiritual tools or sacraments.

There's two general categories of those.

One are what are called the classic psychedelics, and those are the ego dissolving, sort of

merged into unitive states.

Those are like LSD, psilocybin, mescaline, ayahuasca, ibogaine, DMT, things like that.

And then there's MDMA, which some people even argue is not a psychedelic, they'll say it's

an empathogen or an intactogen, it's about touching within or empathy.

It doesn't do the same kind of ego dissolution that the classic psychedelics do, but it brings

material to the surface, and it changes the way we process information.

And so I think you can quibble about whether it's certainly not a classic psychedelic,

but I think MDMA is also a psychedelic.

Marijuana, I would say, is a psychedelic.

Marijuana is closer to the classic psychedelics than it is to MDMA.

One point I like to make is dreams, because then everybody can relate to that.

Dreams are psychedelic.

They bring emotions, feelings, ideas, concepts, in symbolic form a lot of times, or just in

raw emotions to the surface.

So when people hear the word psychedelic, often they are frightened by it.

It's about loss of control.

And it is, to an extent, loss of conscious control, particularly with the classic psychedelics.

And we know with dreams that we can have frightening dreams, nightmares.

But I think that anchoring the concept of psychedelic in dreams is really helpful for

people to know that it's kind of a natural state, and that there are other ways that

you can catalyze it than by going to sleep, and that for thousands of years, substances

have been used in that way.

So you mentioned this idea of bringing something to the surface, which is really interesting.

So can you maybe elaborate the surface and what is there in the depths of things, and

how does ego dissolution fit into that?

Well, Aldous Huxley talked about the brain as a reducing valve, that we have an enormous

amount of information.

So right now there's an air conditioning sound in the background, but that's not crucial

to what you and I are doing, talking to each other, so we kind of tune that out.

There's all sorts of sights and sounds.

There's incoming information in all the different sense modalities, and we have to figure out

what's important to us.

And so the mind, in a way, focuses a lot on what are our core needs, and we filter all

the incoming information that we get towards focusing on what our core needs, and we can

even get to Abraham Maslow and the hierarchy of needs about survival needs, belonging needs,

esteem needs, gone.

So I think what I mean by bringing things to the surface is that we tend to not focus

on a lot of things that are coming, but we also push away things that are difficult emotionally,

difficult cognitively.

We all know that we're on this very short trajectory from birth to death, but we're

not constantly thinking about dying, although that can actually be helpful to focus us on

what's really important.

Traumas are often suppressed, conflicts.

We see in America and around the world a kind of rise of irrationality, where people push

away their logic in order for their emotional tribal needs to be met.

A lot of people are suffering from early childhood traumas of a different kind, or abandonment

issues or anything.

So we tend to focus on just what we need to survive and what we need for work and esteem.

And so psychedelics, by dissolving this ego control or by, with MDMA, kind of strengthening

our sense of self and our sense of self acceptance, we can bring in other information that have

previously been too complicated or too painful.

You don't think of psychedelics as conjuring up something new.

It is more revealing something that is already there.

I think that's a very crucial thing.

So yes, Sasha Shilgen, who is sort of the godfather of MDMA, he sort of rediscovered

it and brought it back into use.

He talked about his first experience was with mescaline, his first psychedelic experience

was with mescaline, and he had a tremendous experience.

But what he said about it was he was having a human experience that the mescaline was

helping him access rather than he was having a mescaline experience.

So that it's not like you pop a pill and you always have the same kind of experiences

everybody else, that the experience is not contained in the pill.

The pill opens you up and you have an experience of yourself.

Sometimes these are experiences that we've never consciously had.

But we can say right now that we know that our body below the level of our conscious

awareness has all these self healing mechanisms, and we don't modulate them to a large extent

by conscious control.

I mean, eventually we are learning more about the mind body and we learn about the placebo

effect, how what we think is the case, but I think that there's experiences that are

below our level of conscious awareness, particularly once we're adults, that are more of these

unit of mystical experiences, sense of connection, you know, I think kids are like this a lot.

We kind of come from the void, you could say, and you're born and you have a different

way of processing information.

One interesting point about that has to do with ketamine, which has been approved as

ketamine for depression.

But it's used for anesthesia and roughly one tenth the anesthetic dose is a psychedelic

dose.

And when it's used in anesthesia, there's what's called the emergent phenomena.

So this is you get enough ketamine for you can be operated on, you're not in pain, you're

not really there, your ego's knocked out, but you can still breathe.

But as the operations get over and then people metabolize the ketamine, there's a process

that they call the emergent phenomena.

It's like as you're emerging from this tranquilized state, and that's where you pass through the

psychedelic phase and they don't prepare people for that.

And what we see is that a lot of adults have difficult times with that.

But children don't seem to have those problems.

Children are a little bit more already in this kind of state.

And so ketamine is used quite frequently in children now for anesthesia.

So all of that is to say to your question that I think the psychedelics reveal things

that are within us.

Some things that are how we process information back when we were children.

Other things that we've never thought of before that are sort of baked into our consciousness.

You know, there's one drug five MEO DMT, it's this toxin from a sonoran toad that many

people consider it to be the most powerful of all the psychedelics.

And it kind of knocks the ego structures completely out of it.

And we experience something different, but it's something I think that's always within

us.

It's a deeper layer.

So we knock out some of the higher cognitive functions and then we experience things in

a different way.

So my sense is that these are human experiences that the psychedelics bring us to.

Yeah, it's really profound, but and that's a DMT is a really interesting example.

So Terence Piquena has talked about these machine elves, right?

And there's this, I think from the people I've heard speak about the experience, there's

a sense that you are traveling elsewhere to meet entities, whether they're elves or not.

So in your sense, you're not traveling elsewhere.

You're just revealing something that's within and maybe it's a particular mechanism of revealing

what's already within.

Yeah.

And I knew Terence.

I spent a lot of time talking with Terence and I do not ascribe to a lot of things that

he was saying.

He was tremendous entertainer and I think he did a lot of really good things and focused

us on the power of psychedelics, but I think I've never seen these quote machine elves.

I think culture is more determinative of what people experience under psychedelics, your

preconceptions than we give it credit for.

And so I think there's a lot of priming that you could say that people receive by stories

from their culture with ayahuasca, it's about jaguars and Amazonian animals.

So I think these machine elves are this construct of Terence that other people do see.

There's actually some people that are very interested in doing a study and they're well

funded and moving toward it to keep people on an IV infusion of DMT for them specifically

to see do they contact machine elves or aliens and what kind of information do they bring

back from these other selves, other places or other entities.

One question is who are we?

Are we connected to everything in the universe?

We certainly know in many cases you talk about waves or particles, the quantum approach.

So I don't interpret experiences that we have of some entity that's somehow or other deep

in our consciousness that's not us.

It's a part of who we are.

So I tend to interpret it in that way.

The question is how big are we?

Yeah.

I mean, that's how many ideas are within us that can be revealed by changing the perspective.

You mentioned physics.

What physicists, especially mathematical physicists or mathematicians do is they reveal truths

by taking a slightly different perspective on a problem that reveals the simplicity of

how it actually works.

In totally new ways.

That's what Einstein did.

Every progress in physics and certainly every progress in mathematics requires you to take

a different perspective and then perhaps that's exactly what psychedelics are doing.

It's not that they're contacting aliens that are elsewhere.

It may be revealing the connection between us and other living life forms or actually

might be revealing a totally new perspective on what life is or what consciousness is and

giving us a glimpse at that even though our cognitive capabilities are limited into fully

grasped and understand it.

So it's just giving us an inkling of that somehow.

And it seems perhaps a little ridiculous, not from a scientific perspective in the sense

that we don't have a good physics of life or physics of intelligence or physics of consciousness,

but getting a glimpse of that is giving us a little bit of maybe an intuition of which

way to head to build such a physics.

Yeah.

Yeah.

I think so.

I think that there's this other concept I guess I would like to talk about briefly, this

Jungian collective unconscious, this idea that somehow or other everything that has

ever happened is still accessible, maybe not with as much data or as much resolution, but

that there's wave resonances so that I do believe that we can have experiences as part

of this human collective unconscious that we're not from our own life.

And that we can, like the holographic realities, that there is a way to gather information

that can be accurate about other times and places through depth investigations of our

own consciousness.

But I think what I tend to believe is that it's because there's emotional resonances

between where we're at now in this life and other kind of experiences that people have

had before.

And we always hear about everybody who talks about past life, they're always kings and

queens.

So I think that's again, you filter things, what you want to be true.

But I do think that there is a way to access information beyond what we've taken in in

our own temporal existence through our own five senses.

In some ways, I really find that compelling the notion that that information is already

there and you're simply just moving the attention of your mind to different parts of that.

Yeah.

I mean, we have that with the radio.

I mean, you know, you've got a frequency, you turn all this information, you could actually

say right now, in the space between us, we have the whole world's knowledge that's up

on the internet.

Yeah.

It's right here.

We don't see it.

We just have to tune in.

What are the interesting differences, would you say, between the various psychedelics

that you mentioned?

Ayahuasca DMT, Acid LSD, marijuana, mescaline, PCP, psilocybin, MDMA.

You mentioned a few of them that are really interesting.

We'll talk about scientifically some of the different studies that have been conducted

on each, but sort of at a high level.

What are some interesting differences?

Well, one of the big ones that people make a big deal of that I think is completely misplaced

is summer from nature, summer from the lab.

So there's this kind of like romantic thought that if it's from nature, it's good.

If it's from the lab, it's somehow tainted by humanity.

And you know, therefore, some people are like all four plants psychedelics.

We see the policy changes that have been happening in a couple cities, Cambridge, Somerville,

quite not far from where we're at now where they decriminalize plant medicines.

So they call it decriminalizing nature.

So I think that there is, from my perspective, certain things from nature are poison, certain

things from the lab are spiritual, even if they don't show up in nature like LSD.

Now there is something LSD is lysergic acid diethylamide.

There is lysergic acid amide, LSA, which comes from morning glory seeds.

So it's very similar.

But at the same time, I'd say I don't buy into that distinction that there's some fundamental

preference.

One of the things that Terence McKenna, since we talked about him, he talked about how if

it's from nature, it's good.

And if it's not, you know, we should be suspect.

Of course, he had a lot of great LSD experiences.

But actually, Terence, in 1984, we were at Esselin with a bunch of other people.

This was before the crackdown on MDMA.

And this was some of the underground therapists and the above ground researchers who were

trying to talk about how to protect MDMA from this eventual crackdown.

And Terence was like, forget about it.

You know, it's from the lab.

You know, it's dangerous.

We have thousands of years of history, all these other things.

And you know, what do we know about MDMA and blah, blah, blah.

And I was like, Terence, you're so unscientific, full of shit, another way to say it is.

And I just said, you know, we need a study of the safety of MDMA.

And so then Dick Price, who started Esselin, I said, I'll put a thousand, Dick Price, he'd

put a thousand.

So Terence was actually the catalyst for the first study with MDMA.

Just because he was so frustrating about how plants are okay and, you know, if it's from

the lab, it's bad.

So that's one distinction.

The other distinction is this sense of classic psychedelics versus things like MDMA.

So to what extent do they dissolve the ego?

And you could say to what extent do they cause visions of the 5HT2A serotonin receptor

subtype, which is responsible for a lot of that, where these drugs are activating.

Now masculine of all the psychedelics, chemically, it's the most similar to MDMA.

It's a phenethylamine, which is MDMA.

So in the 50s, there was the 53, I think it was, the Army Chemical Warfare Service wanted

to look at drugs for interrogations, mind control, nonlethal incapacitance.

They did a study in eight substances.

These were now toxicity studies in animals.

And on the one side was methamphetamine, on the other was mescaline, and MDMA was in

the middle chemically.

So mescaline of these psychedelics tends to have a warmth that MDMA has.

It's not as ego dissolving quite as some of the others.

I mean, it's the main active ingredient in paodi.

It is very psychedelic, very visual.

Another distinction with these different drugs is how long they last.

And a lot of that has to do with the route of administration.

So for example, if you smoke DMT, it takes 10, 15 minutes and you're within seconds,

you're off in another world.

Similarly 5MEO DMT, very rapid.

When you take DMT in the form of ayahuasca, where it's mixed with another substance that

makes it so that it's orally active, then it's a couple hours.

So LSD is 8, 10, 12 hours sometimes.

So lacybin is more like five or six hours or four to six hours.

MDMA is similar.

It's one reason why in our research, we give an initial dose of MDMA and then two hours

later, we give half the initial amount to extend the plateau because we want it to last

longer for people to be in this therapeutic state.

So that's another distinction is how long these drugs last.

Another distinction is which of them come from a religious context, have a religion

built around them.

We have this sense that some people are saying that 5MEO DMT and the Sonoran Toad that they

have this long history of indigenous use, but they don't.

That's all modern.

It's made up and it's kind of a new approach.

However, there was thousands of years of use of psilocybin mushrooms in religious contexts.

From 1600 BC to 396 AD, the world's longest mystery ceremonies, the Ellucinian Mysteries,

sort of the heart of Greek culture, the heart of Western culture, that was a psychedelic

potion called Kikian that seems like it's very much like an LSD like substance, air

got on grain, and LSD comes from air got.

So I think that there are a lot of ways to look at these different substances.

Another distinction is which one of them are being researched right now in scientific

contexts and which are not.

And because of the rise of all these for profit companies and everybody's looking for what

they can patent, what they can claim, the land grab, more and more there are companies

looking at every different kind of psychedelics.

The ones that are most important that are not being researched, Mescaline, but now there's

a company to do Mescaline, Journey Co Lab, Ibogaine, which is crucial for opiate addiction.

There's a new company, a branch of this company, a tie that's going to be looking at Ibogaine.

So I'd say the rise of the for profit companies is making it so that there's just going to

be an enormous amount of investigations into all these different psychedelics.

But what we're going to see is the development of new psychedelics that we don't know anything

about that have not existed yet, because a lot of these for profit companies are going

to want to invent and patent and have composition of matter patents on new molecules.

So I think we'll see a lot of that happening too.

That's really fast.

I mean, there's a lot of doors you've opened and we're going to walk through all of them,

including the research and so on.

But on this one little tangent of the future of psychedelics, so engineering new psychedelics,

can you comment on maybe the chemistry and the biology of how psychedelics work and where

is the space of possible engineering of psychedelics and what kind of things might they unlock

in terms of the possible places our mind would be able to go and the effects of that of improving

health, but maybe at the basic level of chemistry and the space of what could be engineered?

Well, I'll get to exactly what you said.

But you reminded me of a talk I heard by Buckminster Fuller shortly before he died.

And what he talked about is how technology was making things ever smaller, that we are

able to pack more and more information into smaller and smaller spaces and that we're

developing technologies of communications with people we now know the internet and things

like that.

And he said this, that he thought the eventual evolution of this sort of research would move

from this miniaturization to telepathy.

Yeah.

And I was like a shocking thing for somebody like scientific like that to say that.

So will we unlock those parts where I talked about the collective unconscious?

Will we be able to more consciously explore those areas?

So I think that that's a possibility.

There was Stan Groff, who's the world's leading LSD researcher and has been my mentor, his

wife Brigida.

They were talking about stories that they had heard about MDMA that people take.

And then on top of that, they do 5MEO DMT.

And so you get this ego dissolution, but underneath it, you have this sense of ego, sort of sense

of self, of safety, of self acceptance, kind of grounds it.

So Stan was like, that's the future of psychiatry.

That you can watch without the terror of the ego dissolution, the sense that you're losing

your mind or you're going crazy or you're dying or, you know, that you have this grounded

sense of safety while you're dissolving your normal sense of how you see things.

And being able to engineer in a fine tuned way that exact experience, maybe fine tuned

to the person as opposed to sort of this manual potion that's through experiment.

Although I don't know about fine tuning things to the person in the sense that we believe

there's this inner healer, this kind of inner healing intelligence.

We talked about it, the body repairs itself.

So I think we more need to create safety for people and then what emerges will be customized

to what they need to be looking at from this inner healing intelligence.

At the same time, we will move to, you know, we hear so much about the new approaches to

oncology where, you know, you do a genetic analysis of different kind of tumors and

then you have certain kind of chemotherapy agents and you do like personalized chemotherapy.

I think we will have more like personalized psychedelic therapy, but it'll be more like

a sequence of different drugs that people go through over an extended period of time.

And then you kind of customize what's next and sometimes you'll combine different drugs

together like this five MEO DMT and MDMA or a lot of times people do LSD MDMA combinations

or psilocybin MDMA combinations.

Therapy and, you know, it's not my strength, I'm more into clinical applications and policy,

but I can say that from what I've learned from reading from others and research done

by others that, you know, different psychedelics have an impact on different neurotransmitters,

different other parts of energies in the brain.

The default mode network is what's considered to be like our sense of self, you know, and

it's this, it's part of the brain that sort of is what I described before, scanning the

world and filtering information for what's really important to us and both focusing us

on things and also helping us to ignore a lot of things.

And the classic psychedelics all weaken the energy in this default mode system and therefore

you get this flood of information that you're not normally paying attention to.

And then you start seeing in more creative waves or more connected, you actually move

to beyond the verbal kind of thinking into sort of symbolic thinking a lot of times.

And that's where you sometimes get these mystical sense of connection, how it's all one and

you get the sense also of how big the universe is and how small each one of us is.

So there's a lot of work that Sasha Shilgen and Albert Hoffman who invented LSD and first

synthesized psilocybin on what they call structure activity relationships.

What is the structural molecule and then how do you predict what that new molecule that

never existed before is going to do once you actually take it.

And you can get close, but you never really know until you actually take the drug.

And the way that Sasha ran his experiments is that he would take the drugs himself first

in low doses and he would sort of step up the doses to have more experiences.

If he thought it was valuable, he'd share it with his wife Anne.

But then what they would do is if they both thought it was valuable, they had a group

of 12 people that they were with for many, many years and they would distribute these

new drugs to these 12 people and they would get the different perspectives.

And he thought that 12 was like a minimum number because we're so unique how each of

us see things.

But then you kind of get a little bit of a consensus on how a lot of people are going

to see it.

And then if that 12 people were positive about it, then they would turn it over to Leo Zeph

who we called the secret chief, the leader of the underground psychedelic therapy movement

and then he would start exploring it in therapy.

So there's still a lot of mysteries as far as structure activity relationships and it's

not going to be the case that people go into the lab and they tinker with molecules and

they know exactly what they're going to get.

And a lot of it has to do with not so much chemistry as morphology, you could say the

shape of the molecule and how does that interact with receptor sites.

And so we're getting better at modeling all of that.

And how does that interaction relate to the morphing of the human experience and deeply

understanding that perhaps there's no equations yet for that kind of thing.

You really have to build up intuition by experiencing it.

And over time, the sort of subjective self report like trying to build an understanding

of the effects of the different chemistries.

Yeah.

Yeah.

You can have approximate ideas, but to know exactly.

So when I first tried MDMA, which was 1982, and this was after I had done lots of LSD

and mescaline and mushrooms, I was shocked at how different it was than these other substances

and yet how profound it was.

So are there a whole new kind of categories of classes of drugs that we're not aware of

that would be not so much this like eco dissolution or emotional, well, what MDMA does is reduces

activity in the amygdala, the fear processing part of the brain.

So it's not just chemistry, but it routes energy throughout the brain in a different

way.

It increases activity in the prefrontal cortex.

So you think more logically though, that I think has an enormous impact on the effect

of MDMA.

The other thing it does is it increases connectivity between the amygdala and the hippocampus.

So it helps facilitate processing of things into long term memory.

And with PTSD, trauma is like never in the past.

It's always about to happen.

So will we one time develop drugs that would even be specific to certain kind of memories?

We're working with a woman, Rachel Yehuda, who is at the Bronx VA.

And she's done some studies that are with the epigenetics of trauma.

So she's worked with Holocaust survivors and their children.

And she has identified epigenetic mechanisms by which trauma is passed from generation

to the generations, sort of like set points for anxiety, fear, certain things like that.

But the question is, can you actually transmit memories from one generation to the next?

Now this is not DNA changes, which happen over a very long period of time and evolutionary

scale.

But within one lifetime, within some experiences, your epigenetics, what turns on the genes

or turns off certain genes, that can be impacted.

And that's what we know now can be transmitted from generation to generation, either by the

father or the mother through the sperm or the egg.

So it's pretty remarkable.

So what Rachel's going to try to do is MDMA research for PTSD and look at these epigenetic

markers before and after and see if they change as a consequence of therapy.

So will we develop one day certain kind of chemicals that will be able to bring certain

kind of memories to the surface?

That's not inconceivable.

The epigenetic angle is fascinating that there will be these epigenetic perturbations that

lead to memories living from one generation to the other.

And then bringing those memories to the surface and using that as signal to understand what

exactly the psychedelics bring to the surface and not.

Yeah.

Now the other portion of that though is culture.

I mean, culture is where we store all these memories and in the stories that we get passed

out.

Especially with a lot of shared, you talked about the Holocaust or World War II, where

it is deeply ingrained in the culture, the impact of those events and sort of an aggregate,

the different perspectives on that particular event create a set of stories that you can

plug into.

And they kind of resonate with some aspect of you that creates a memory that's connected

to, like when I think about World War II and the Holocaust, I think about my own family.

But in some sense, it's also resonating with stories of many others.

So it's like somehow the two echo each other.

And I'm just providing my own little flavor on top.

The meat of the stories are probably those that are shared with others.

Just plugging into the collective unconscious, that's really fascinating, really plugging

into precisely plugging into particular memories as a way to deal with trauma and PTSD, that

kind of thing.

Yeah.

I'll just add that the most important dream of my life ever was of a Holocaust survivor

telling me that he was miraculously saved from death, and he knew that he was saved

for a particular purpose, but he never knew what that purpose was.

So in the dream, I'm seeing him on his deathbed.

And then he shows me whatever happened to him during the Holocaust.

And then we're back in the room on his deathbed, and he says, well, I know what my purpose

was now.

And I'm like, oh, great.

What was it?

I was just to tell you to be a psychedelic therapist and to study psychedelics and bring

back psychedelic research.

And I thought to myself, I've already decided to do this.

You can lay this on me.

I can say yes, and then you can die in peace.

And then he died in front of my eyes in the dream.

So I think that that kind of cultural transmission that I got from when I was really young then

manifested in this dream, and that was this story about how people can be incredibly vicious

and can be very motivated by irrational factors.

And so I just feel that this kind of multigenerational transmission of this story of the irrational

being a murderous factor and something I needed to respond to was deeply ingrained.

And I would say my guess is more culturally than this epigenetic mechanism.

Yes.

Yeah.

But your sense is that whatever stimulated a certain part of human nature in World War

II, especially in Nazi Germany, but also in Stalinist Soviet Union, still is within

us, within all of us.

Just like what we're saying, we embody quite a lot of things.

And one of those is whatever the capacity for evil seems to be one of those things.

Yeah.

There's a quote from Carl Jung from just a few years before he died.

What he says, and I'll just paraphrase it, is that we need to understand psychology.

We need to understand who man is, that the greatest danger to us is man.

There are no other dangers, really, that impact our species.

And then he goes on to say that we are the source of all coming evil.

Now, this was 15 years or so after World War II.

But yeah.

And I'd say one of the most important psychedelic experiences of my life was a DMT experience.

So Terrence was there, Ralph Metzner, Andy Weill, a few others.

And we were sitting around at Estlin smoking DMT.

And under the influence of DMT, which now this was the first time I've ever smoked DMT,

I had this super rapid fraction of a second, like dissolving of everything that I, well,

first off, I saw a horizontal line, then I saw a vertical line, then it turned into

a color red, then it was red, then it turned into cubes.

Then it turned into like an MC Escher kind of like, I don't know, you know, didn't make

logical sense.

And then I was gone.

And then it was just this period of 5, 10 minutes of just feeling part of this enormous

wave of billions of years of evolution and how I had this sense that in my innermost sense

of who I am uniquely individually, this inner voice that's talking to me, that I didn't

develop English, that it's like a gift to me from millions of people.

So that even in my most innermost sense, it's not just me.

It's the product of everything that came before me, I'm part of this bigger system.

And then I just thought, wow, just how many billions of years does it take to reach this

point of self awareness and all this and it was glorious, beautiful.

And then I had this thought, and this is where this kind of intellectual honesty, I guess

you could say, I just thought, well, if I'm part of everything and everything's part of

me, then it's not just the good parts that Hitler's part of me too.

And that was just this shock, like a stone sunk, you know, and I just was very moody

for the whole next day.

But it was that acknowledgement that each of us carries these potentials and what we

activate is what matters, but what our potential are is the whole full range of things.

I don't know if you can comment about the DMT trip itself and what it's like starting

from the very basic geometric shapes and then launching yourself into the context of the

enormity of space and time and human history.

Is there anything else to be said about that kind of visually or physically or emotionally

about that journey, what it's like, that brief journey that reveals so much?

Well, I was with a group of people.

The way we were doing it was, you know, each of us would smoke DMT, have 10, 15 minutes

experience while we closed our eyes and everybody else was just chatting and then the person

who did the DMT would come back and tell their story of what happened.

And then we'd think about it for a bit and then pass the pipe to the next person.

And so this was like a whole evening, you know, and even the sorry to interrupt, even

the conversations themselves then is part of the experience.

Exactly.

Yes.

Yes.

Because it's also what you bring back.

Right.

I mean, I think that's particularly for therapy, you know, it's not so much about what the

experience is, but it's what you bring back and what do you integrate.

And then also, how do you learn how to do these things on your own without the drugs?

There is this way, because we're saying it's sort of a core human experience.

The drug is the mediator, but can we do this on our own?

And once you've seen it and felt it, then you have a little bit better sense to recreate

it on your own.

Although, you know, I've had dreams where I've been doing LSD and tripping.

I was just incredible.

And it was, I was tripping in my dreams, but I had not taken LSD.

So there's this way in which we do that.

So I would say that from the DMT experience, the sense of safety, that's what I was trying

to get at with this, the group of us and this group of friends trying to do this common exploration

that if you have this sense of safety, you're incredibly vulnerable because you are giving

up your awareness really of what's happening around you.

I think there's, what we're finding is that in our psychedelic research for PTSD and what

we see with the vaccines, that even African Americans are reluctant to volunteer for vaccines

because they haven't had that sense of safety from the medical establishment.

They don't volunteer for psychedelic therapy even as much.

So the overlay has to be this sense of safety as you become vulnerable and looking inside.

You're not, I was just actually told about how there's a lot of work being done inside

prisons to teach mindfulness.

And you know, so one of the, Charlene who's my assistant is trying to do work on helping

people in prison with trauma, potentially one day with MDMA or meditation or mindfulness.

But one of the exercises was teaching people to, okay, here's how you deal with stress.

Just close your eyes and deep breathe.

And what Charlene was saying is people don't close their eyes in prison.

You don't feel safe to do that.

So all that is just to say is that the context is the most important factor.

So while I'll talk about the DMT experience, the context was this supportive sense of safety

that I could be completely vulnerable and out of any kind of control women, I think,

you know, often are less safe in this way than men because of all the sexual assaults.

But what it can do by taking the ego orientation offline to some extent, it opens you up to

much more and to make a bigger point of that.

We could say that it's very similar to the Copernican revolution.

And you know, people thought that the earth was the center of the universe.

And you know, the inquisition murdered people that questioned that.

Father Bruno burned at the stake.

Actually, one of the things he said, I think that's worth all these years later saying

is that when the inquisition sensed him to burn at the stake for espousing this idea

that the earth was not really the center of the universe, he said to the inquisition,

he said, your fear in sentencing me is greater than my fear in being sentenced, that their

worldview was so rigid that they had to wipe out anybody that would question it.

And so this idea of psychedelics displacing our ego is the center of the universe.

And to realize that we are just rotating around something much bigger than our individual

life, you know, our ego is designed almost to protect this body while we're alive.

And you can understand all the good reasons why that is.

But it also disconnects us from this bigger reality.

And so the psychedelics, DMT, by knocking this sort of ego orientation or the default

mode network offline, you open up to the bigger sweeps of history.

So in that place of safety and vulnerability, in that fascinating group of people, when

their ego was dissolved in this way, did they have similar experiences?

Is there different places that their minds went?

Yeah.

So once I had this kind of shattering experience that Hitler's part of me, you know, no one

else in the group had that.

Probably a lot of them have maybe had that before or they realized that they're not just,

you know, the good, the white hat, good people and that they're all good and they're, you

know, got to fight against the bad people, you know, so, you know, people will go in

different places.

And not only that, if you do it again, you'll go into a different place than you went to

the first time, unless you have not resolved the issue.

So I had a sequence of LSD trips that were very difficult, but it was like coming to

the same sort of conundrum, the same challenge that I was unable to overcome this idea of

letting go and really fully dissolving, letting the ego fully go.

And I would have this sequence of trips over a couple months where I would reach this point

where I was too scared to move forward and I would just be holding on.

So there are repeated themes sometimes.

What Stan Groff has said, which I find very beautiful, is that the full expression of

an emotion is the funeral pyre of that emotion.

And what that means is if you can fully let in something, then the essence of life has

changed is that it moves on, that everything's in motion, and if you can fully experience

it, even if it's a sense that you're going to be trapped in eternity in this hellish

state, if you surrender to that, that's the way out.

You know, this full experience of something is this funeral pyre of that emotion.

And so that runs against a lot of what modern psychiatry is doing too, which is to suppress

symptoms and to, instead of supporting people to kind of explore these insecurities so that

then they can contain them and then they can move on.

So yeah, resistance is not a way to make progress.

Right, right.

Although in one of the reasons why we do the supplemental dose during the MDMA or why there's

advantages in a 10 hour LSD experience is that you have a lot of opportunities to come

up against this resistance that may be too difficult to deal with, and then you kind

of push it aside, and then a couple hours later you come back to it or you come back

to it.

Press news every once in a while if you're not ready.

It's hard to do that.

I think with MDMA, you can negotiate.

That's I think a part of its safety in a sense, you can have this like, oh, I should be talking

about this, but we're not feeling this, but it's too much for me now.

You can push it away.

But with the classics psychedelics, this kind of membrane between the conscious and

the unconscious, that once you take the drug and it weakens this membrane and things are

coming up, it's very difficult to negotiate with it.

The key to successful classics psychedelic trips is surrender.

You've talked about that you first began to reconsider the negative health myths around

psychedelics when you learned that the book One Flew Over the Cuckoo's Nest was written

by Ken Keezy when he was in part under the influence of LSD.

So how do you think LSD helped him, Ken Keezy, in writing that incredible book?

There's a process that's called semantic priming.

And so what that means is that I say night, you say day.

There's kind of normal patterns of you say one word, what kind of words come to you next.

And so they've done some research, meaning scientists have done some research where you

give people a psychedelic and then you do this semantic priming.

And what you find is they have a wider range of associations than they normally would when

they're not under psychedelics.

So I think for Ken Keezy, he was able with psychedelics to get like a deeper kind of

emotional connection to some of these states of mind that people were in this mental institution

and that he could explore them more in depth and more eloquently.

And also one of the things he talked about was the fog machine was how people's minds

were sort of clouded by the people that ran the institution and the fog machine would

be coming in.

So I think the imagery and the metaphors that he used a lot in the book could come to him

during LSD experiences.

And then now he wasn't doing very, when you're writing, you have to be literate, you have

to be able to write.

So it would be more like beginning and ends of LSD trips instead of at the peak.

But I think you would get a lot of these, the feeling tones or the images, the metaphors

I think he would get, these extent, also LSD lasts so long, you can get these extended

focus and you can really elaborate on images.

And so much of psychedelic experiences are poetic and metaphorical.

I mean, you can take veterans who've never read a book of poetry in their lives.

And under the influence of MDMA, just what they describe, the imagery and the way they

describe their experiences, metaphorical, poetic, it's incredible.

And so I think that Ken Keezy was able to channel what LSD did to his mind in a way

that most people couldn't do, that he did because he was trying to write this novel

and because he was so brilliant.

Yeah, I mean, we'll talk about psychedelics and treating in bringing some of trauma to

the surface and dealing with all those kinds of things.

But there's something also to the opening up of creativity for whether it's for writing

purposes or for in my world, for engineering, for invention, innovation and invention itself

is a deeply creative process.

And it's fascinating to think with the aid of psychedelics, what kind of ideas can be

brought to life?

Yeah, well, we have the whole phenomena of a lot of the people in Silicon Valley and

else microdosing psychedelics in order to have a little touch more of this creative

approach to things.

I would love it to see if it was, that's more like Terence McCann territory, correct me

if I'm wrong, but I would love to sort of more scientific to where there will be the

rigor of saying how to do it effectively, how to sort of understand sort of not just

almost to take the full journey of creative exploration and to do it for prolonged periods

of time, you know, for years, you know, lifelong kind of part of your life of how it empowers

creativity.

I think, of course, you start with helping people deal with trauma.

And then the next step is people who have moved past their trauma and are trying to

do something, create something special in their life.

How can then psychedelics empower that?

Yeah, now that also just to not shy away from anything controversial, that has that gets

us to this idea of psychedelics for vision quest, particularly for younger people.

You know, when you're sort of moving into this adulting kind of phase and you have to

figure out what are you going to do with your life?

There's so many options.

A lot of people, of course, feel constrained that they have very few options.

But I think this idea of psychedelics as a way to help you find your calling or find

your vision or find your unique leverage point, I think we'll see that more and more as our

culture evolves and gets healthier around the use of psychedelics.

So it's both the science having the rigor of understanding how to do it safely and the

culture catching up to the fact that this is both safe and like very useful.

Yeah, although I would question this idea of safety.

So we can understand physiological risks and we can minimize them.

And I think there's very minimal physiological risks from the classic psychedelics, virtually

none were for even MDMA under safe conditions.

Psychological risks are harder to address, but we can do that through the sense of safety

and support.

But I think there's a level of risk there that we shouldn't overlook.

And so, you know, to make a drug into a medicine, what we have to do is prove to the satisfaction

of the FDA and other regulatory agencies that things are safe and efficacious.

But even though they use those words, proving safety and safe and efficacious, it's in relationship

to the disease that you're trying to treat and you accept a certain amount of risk.

So it's the risk benefit ratio rather than pure safety.

Yeah, absolutely.

Let me ask you about Ken Keezy a little bit longer because he was also part of Project

MKUltra.

Yeah.

Yeah.

What was Project MKUltra and what lessons we should take away from it?

Well, MKUltra was a program by the CIA.

What they were looking at was, can you take these drugs, these psychedelic drugs and weaponize

them in different ways for interrogation, for true serums, for exposing somebody before

they give a big talk to something like LSD and then they, you know, can't talk or make

a fool of themselves or can you spray LSD over the battlefield and have everybody tripping

and drop their weapons and then you just walk up and, you know, nobody dies and you've won,

you know, the battle.

So...

It's a fascinating concept.

Yeah, they call it nonlethal incapacitance and I think that's how it's...

One way to win a war is to enforce peace.

To get everybody not caring about the war, but yes.

Well, I think Gandhi said something even better, which is that the true way to win a war is

to turn your enemy into your friend.

Yes, that's a beautiful way to put it.

But MKUltra was really nefarious and it was part of our military and it was done in secret

and they would dose people against their will.

I mean, one of the most infamous things was that they had a house of prostitution in San

Francisco and they would have one way mirrors all the stuff and then they would just dose

people with LSD, you know, they would have the prostitutes dose these guys with LSD and

observe what they would do and how they would act and the CIA actually for a while was dosing

each other secretly and then there's a famous case of this fellow Olsen that either jumped

out of a window or was pushed, he might have been killed, he was a CIA guy and they gave

him LSD and then they're trying to see, can they break him down and get him to tell secrets

and I think he felt uncomfortable with what happened to him while he was under the influence

of LSD and whether he was pushed or not, I don't know if we'll ever know.

But MKUltra was violating people's human rights, it was done in secret and the irony

of it is that Ken Kesey is one of the people, one of the main early people that got LSD

in this context and then he was one of the main people that helped inspire the hippies

to use psychedelics to oppose the Vietnam War.

So I think the CIA kind of in many cases, things get out of their control, what they

think they can do and it turned into be a disaster for them.

I think there was some thought that some of the people at the CIA had is that if you can

turn people inside, take drugs and they just focus on their internal experience, they're

not going to be involved politically, it's a way to sort of take people offline and what

I don't think they countered on is that when you're offline and you have these unit of

spiritual experiences and you realize how we're all connected, then why do you want to go

out and kill these Vietnamese and put one dictator over another dictator, dictators on both sides

in North Vietnam and South Vietnam, why are we doing that?

So MKUltra has a very disreputable, we're learning more and more about what they did

and one of the unintended consequences was Ken Kesey and not only that, but then the

Grateful Dead who began at the acid tests that Kesey was helping to organize and out

of that emerged, you could say, just this incredible psychedelic culture and you look

at the bands that began in the 60s and which ones have really survived to this day and

the Grateful Dead has survived longer than most any other band, I mean some of them have

died and all, but it was like the tightness, the sort of telepathy we talked about before

that they could just get so tuned in to each other and each other's energies and they could

do improvisations and they could do this incredible work that I think the sustainability

of the Grateful Dead as a group was a testament to the power of the LSD experiences and that

might have never happened if not for MKUltra.

But can we talk about darkness a little bit, so Ted Kaczynski, the Unabomber was allegedly

part of the MKUltra studies while at Harvard, do you think this is true?

Do you think it had an impact on him psychologically, intellectually, and so on?

I do think it's true and I do think it had an impact.

So we talked before about are these drugs somehow rather producing a certain kind of

drug experience or do they bring out what's within?

So we have this experience on the one hand Kinkisi and he sort of took positive things

out of this.

On the other hand, we can get this opposition to the modern world to technology and to the

point of creating bombs to try to go after it so that the experience is not in the drug,

it's this interaction between the drug, the person, the context.

And so we can heal people with psychedelics or people can be driven crazy with psychedelics.

It depends again on the context.

And so I think it's both these things can be true.

And I think it was really good that you kind of highlighted this, that there is this polarities

and that it's not in the drug.

It's in the other factors and it's who they were beforehand and then how you use that experience.

So all that's to say is if we put LSD in the water and everybody were to get it, it doesn't

mean that all of a sudden everybody's going to have a mystical experience and then that's

all we need to do and humanity is spiritualized or end war and all of this.

It's not about the drug and that actually is why for me, we've also talked about engineering

new psychedelics and all the people that are going to be trying for profit companies

to develop and patent new psychedelics.

For me, the most important challenge is new cultural contexts that can create legality,

safety, support for the existing psychedelics that we already have.

I mean, we have so much incredible tools in these existing psychedelics that it's more

about creating context for them to be used in safe medical or personal growth or recreational

even with harm reduction, all these different ways.

That's more important to me than finding some new molecule that's somewhat similar, somewhat

different, but it can be patented.

So it's the social context.

So I do believe that Ted Kaczynski was part of MKALTRA and I think it affected him in

a negative way and that's a cautionary tale that it's not in the drug, it's in the context.

The context of person, still it feels like if viewed from a therapy perspective, perhaps

there was a way to use psychedelics to help Ted Kaczynski find a path out of the darkness.

I think so and I think that this is where I think MDMA comes in in a way that MDMA is,

he felt very isolated and very much out of society in some ways.

MDMA stimulates oxytocin, which we haven't mentioned, which is the hormone of nursing

mothers of love and connection.

It provides a lot of this sense of self acceptance and safety and wanting to be in relationship.

There's Gul Dolan is a neuroscientist at Hopkins.

She's given octopuses, MDMA, they're solitary creatures except mating season, which is not

very often, but you give them MDMA and they become more interested in hanging out with

other octopuses.

For people that have had difficult psychedelic experiences, MDMA helps them integrate them.

We've worked with people that had a difficult LSD experience 40 years before and are still

able to get back to that under the influence of MDMA and work out some of the conflicts

that they weren't able to resolve all those decades before.

I think that psychedelics could have been helpful in a different context for Ted Kazinksi,

but the other big part of it is that people have to be willing to cooperate with the experience.

We talked about resistance.

People can resist these things.

The saying is you can bring a horse to water, but you can't make him drink.

This is about how people have to be willing to go to these spaces.

The essence of our therapeutic approach is that we help people to heal themselves, that

we are not giving them the healing.

It's a flip on the power dynamics that existed, you would say, in the 50s and 60s.

My dad was a doctor and the doctors were gods and whatever they said was right.

We no longer, of course, believe that, but for a while, psychoanalysis with Freud, that

they gave the interpretation to the patient, the patient couldn't help themselves, but

they would do the free associations and then psychoanalysts would see these conflicts and

would be the one that does the healing, would give this interpretation and that would open

things up.

I think it's this idea of empowering people to heal themselves.

If Ted Kazinksi had been in a therapeutic setting with psychedelics and if they'd had

something like MDMA available or MDA, which was popular during the 60s, which is a more

like MDMA LSD combination, the outcomes might have been different.

Let's take a step into the world of studies.

Timothy Leary, who was he and what were the most important ideas you've learned from him?

I did have the opportunity to get to know him personally and to spend some time with

him.

Timothy Leary, well, let's start with Nixon saying he's the most dangerous man in America.

That's a good place to start.

Why did Nixon say that?

It's because of this turn on, tune in, drop out.

Timothy Leary was just an incredible advocate for think for yourself, question authority.

Those were things he said all the time.

Think for yourself, question authority.

He was a rebel.

He was kicked out of West Point.

He was a psychologist who was at Harvard for three years from 60 to 63.

Before he got to Harvard, he had an experience with mushrooms in Mexico.

He said he learned more in that experience than he'd had in his entire academic career

before then about how the human mind works.

He came to Harvard wanting to do research into psychedelics.

He did some very important studies, both of which, well, one was called the Good Friday

Experiment, which was whether psychedelics in religiously inclined people taking psilocybin

in a religious setting, whether it could produce a mystical experience that took place at Marsh

Chapel at the Boston University.

Because it's a little bit subjective, or you could say entirely subjective, what people

describe happens to them.

He wanted to do another study, which would be a more objective measure, and that was

called the Concord Prison Experiment.

That was the thought, if you can give people psilocybin, mystical sense of connection type

experiences while they're in prison, when they get out, they'll be more pro social and

they'll have reduced recidivism.

Tim did that.

He also did the naturalistic studies of giving loads of people psilocybin and writing down

what their experiences were, the range of experiences.

Later on, in his time at Harvard, they started doing LSD.

LSD is more cerebral, longer lasting, not as reassuring in a way as psilocybin.

Sometimes he used to say that if they'd never got into LSD, they'd still be at Harvard with

the psilocybin.

He was a great American psychologist, but then he got tired of the psychology game, you

could say, or he would say that.

He got more and more interested in cultural change and various musicians and artists and

all sorts of people started coming to him for the psychedelic experience that they are

in a way, for creativity, for other things.

He started hanging out with all sorts of famous people or creative people and he stopped going

to classes a lot and Ram Dass, Richard Alpert had given LSD to a student that Ram Dass

was courageous enough to admit that he had sexual interest in.

They weren't supposed to give it undergraduates.

That was about the only time that they ever did it and psychedelics just getting more

and more controversial even in the early 60s, eventually got kicked out of Harvard and then

he became a cultural icon for the counterculture and was hounded by the police and Nixon and

spent a lot of time in jail.

He's an incredible person.

One thing that Ram Dass said is that Richard Albert Ram Dass said, I'm a rascal but Leary

is a scoundrel.

What's the distinction?

A scoundrel is like in good fun, a scoundrel is like you can't quite trust them, I think.

Yeah, it's a spectrum of sorts.

Yeah, I think that Leary was someone who a little bit got addicted to media attention.

But I think that overall he gets blamed a lot for the backlash against the 60s, the shutdown

of psychedelic research.

I think that he is unfairly blamed for a lot of that.

I think when you look back at the 60s, the common narrative is that it was because psychedelics

going wrong.

People took psychedelics, they weren't prepared, they had emotional breakdowns, they went psychotic,

they killed themselves, they did this or that, different problems of people taking psychedelics

in context that they didn't feel fairly safe in or just they weren't prepared or they didn't

know how much they were taking or all this.

So the backlash was because psychedelics going wrong, but I think the real reason, well,

that did happen.

I think the real reason is psychedelics going right and people having this sense of connection

and then the opposite of what the CIA was hoping that it would turn people inward and

take them away from political struggles, it actually motivated people.

Once you actually have these psychedelic experiences, your attitude towards death changes also.

This idea of death becoming an intrinsic part of life, it's a natural cycle.

It's not so much.

So I think people realize that while there's this billions of years of evolution, infinity,

whatever that means in terms of time, that we're here for a very limited time and they

end up wanting to use their time well, they have a lessened fear of death and they want

to build this paradise on earth here now instead of later.

So a lot of people really did get motivated to challenge the Vietnam War to work on the

environmental movement, civil rights movement, women's rights movement, anti militarism.

And it was that challenge to the status quo that caused the backlash.

So Leary is someone who in 1990, we had a, now maps, I started in 86.

So in 1990, we had this conference to raise money out in California and Leary was there

and Ram Dass was there and Ralph Metzner was there and Nandi Wao was there and Terrence

McKenna was there and Dennis McKenna was there and all these.

But there was one point where Tim was speaking and afterwards I was asking him some questions

and I said, do you have any advice for us on how to work with the government and how

to bring these psychedelics forward?

That's what we're trying to do.

I've got this nonprofit for it.

We're trying to do this research.

What is your advice on how to bring this forward and how to work with the government?

And he said, fuck the government.

He said, I am so far past asking for permission for anything, but I'm glad that you're doing

it.

And then he held up my hand like, you know, like passing the torch.

Wow.

So it was, and that's one of my favorite photographs of me and Tim where he's sort of like, but

it was the after this, fuck the government.

And I'm so far past asking for permission for anything, but I'm glad that you are now.

I did followups to the Good Friday experiment and I did followups 25 year followup to the

Good Friday experiment, about a 34 year followup to the Concord Prison experiment.

What I discovered in some ways I would say is the key to the sixties, what I just told

you, but in the followup to the Good Friday experiment that I did in the eighties for

my undergraduate thesis at New College in Sarasota, Florida.

I eventually found 19 out of the 20 people.

It was just, it was, that was an enormous challenge because their names were all lost

and just took forever, years and years and years to find them all.

But I discovered that those people that had the psilocybin experience in the midst of 25

years later with Nancy Reagan and Ronald Reagan, and if there ever were there a social pressure

to disavow the validity of the psychedelic experience, that was then.

And instead they affirmed it, that they thought with all of this years of hindsight now looking

back, they thought it was a valid mystical experience.

But I discovered that one of the persons who had the psilocybin had this experience during

the Good Friday service that Reverend Howard Thurman was the minister.

He was Martin Luther King's mentor and Reverend Howard Thurman was the minister at Boston

at Marsh Chapel.

Martin Luther King got his PhD at Boston University.

And Howard Thurman had spent time with Gandhi.

And so he was really kind of this hidden person behind the civil rights movement about nonviolence

as their strategy.

But he was interested in the political implications of the mystical experience.

So he permitted this experiment to take place.

And there were 20 Divinity students from Andorra Newton in the basement and 10 experimenters,

all the people on religion and psychology, like Houston Smith and Maltrys and Clark and

Leary and Rom Desmond and others were there as a support part of it.

And the sermon was like three hours later.

We actually have a three hours long, we actually have the original sermon from the Good Friday

experiment from Howard Thurman up on our website.

It's incredible.

But part of it was tell people there's a man on the cross.

And this one person sort of heard that and he thought, okay, I got to do that.

And Howard Thurman was such a dynamic speaker and he said, I got to tell people there's

a man on the cross.

And so he said, what am I doing here in this basement chapel listening to the service?

I got to go tell people there's a man on the cross.

So he went, they thought he was just going to the bathroom, but he ran out the door.

He's running down Commonwealth Avenue and Houston Smith and Tim Leary go after him.

And he had thought that since he should tell somebody, he should tell the president.

Like why not?

And then he realized, well, the president's in Washington, you know, here in Boston, I'll

just tell the president of the university.

So anyways, running down the street and Leary and Houston Smith go after him and he doesn't

want to go back inside.

They finally get him.

He's not hit by a car.

But they end up giving him a shot of Thorazine.

What's Thorazine?

Thorazine is like a major anti psychotic drug, it's a horrible drug, but it knocks people

out, tranquilizes them.

We would never do that today.

We don't abort a difficult experience like that.

But in any case, they hid that.

That was not part of the write up of this experiment.

So what they did is, in a sense, a little bit exaggerated the benefits, it later became

out three years later after the experiment or four years in Time Magazine, it said everybody

that got psilocybin had a mystical experience.

It wasn't true, not everybody, eight out of the 10 did, but not all 10, not this guy.

And they minimized the risks.

So there was a bit of that.

I think Tim was reckless in that way, was underplayed the risks and over promised the

benefits.

And then the Concord Prison experiment, it turned out that Tim had fudged the data completely

and it wasn't really successful.

So I faulted him for that, but the outside world was doing the opposite.

It was exaggerating the risks and blocking research.

So he felt justified to fudge the data because the outside world was fudging in a sense,

the response to the...

Yeah, exactly.

So that presents a very nice context.

Not the government, but I'm glad that somebody is fighting the good fight from within and

doing it the right way, which is where you are.

So the 80s, let me ask, what is MAPS, the Multidisciplinary Association for Psychedelic

Studies, and what is its mission throughout the years, throughout the decades?

Yeah.

So MAPS is a nonprofit organization.

I created it as a nonprofit pharmaceutical company.

I created it in 86 after DEA, the Drug Enforcement Administration, criminalized MDMA in 1985.

And that was after they started trying to do that in 1984.

And as I mentioned, this Terence McKenna's motivating us to do this safety study.

So we did that in preparation for this eventual crackdown because MDMA was called Adam, used

as a therapy drug, but it was also beginning to be sold as ecstasy as a party drug.

And that was taking place in public settings and bars.

And so it was inevitable that the crackdown would happen.

And so I had a nonprofit connected to Buckminster Fuller, Earth Metabolic Design Lab, that

we used to support this lawsuit against the DEA to block them from criminalizing MDMA.

We were winning in the court of public opinion and winning in the court.

The DEA freaked out and the emergency scheduled MDMA in 85.

The handwriting was on the wall that they were not going to permit the therapeutic use

to continue because it gets in the way of the narrative of the drug war.

And these are terrible drugs.

So in 86 is when I started MAPS as a nonprofit pharma because the strategy that I realized

is that Americans are open to medicines, you know, that tools to ease suffering.

That was the opening wedge, the opening door to changing attitudes.

And it would be through science, I would say that my religion is more science than anything

else.

Yes.

And, you know, culture and religion are metaphorical, but often too much, they become literal, but

I felt that through science, through medicine, there would be a way to bring these drugs

back to the surface.

And the mission was always this mass mental health.

This idea that what we need is to spiritualize humanity.

Einstein said the splitting of the atom has changed everything except our mode of thinking.

And hence we drift towards unparalleled catastrophe, which shall be required if mankind is to survive

as a whole new mode of thinking.

So what is that new mode of thinking?

My presumption is that it's more of this mystical sense of thinking that we're all connected.

And then if we realize that we're all connected, we're not going to blow up the world.

So a lot of people say that, you know, if we could just give LSD all to the world leaders,

that would be, you know, then they'd have these spiritual experiences, the world would

be better.

But actually I had a ketamine experience the day after that DMT experience I described

with the inner Hitler.

This ketamine experience was, I was above and behind Hitler as he was giving a speech

like in the Nuremberg rallies kind of thing.

And I was trying to think, how do I get into his head?

How do I undo what he wants to do?

How can we deal with him?

And I realized this whole new thing about the Heil Hitler salute and, you know, he

would like push energy out and then everybody would do the salute back to him.

And so it's like the one to the many and the many to the one giving all these people giving

away their power and then how it would just sort of ratchet up in intensity, like these

vibrations.

And I realized there's no way to get into his head.

This idea we've talked about before about, you have to be willing.

So what that sort of helped me understand is that the strategy has to be mass mental

health.

It's not about changing a few leaders.

We need to change the mass of humanity to this new mode of thinking, this new spiritual

way.

The maps was a nonprofit pharmaceutical company focused on psychedelics.

Big Pharma wasn't doing this work.

Government wasn't funding it.

So the only source of funds I thought would be through nonprofit donations.

And that's been true up until just a couple of years ago now that we have the rise of

these for profits, but that's because we've cleared out the regulatory obstacles.

We've got more scientific data about the benefits funded through philanthropy.

We've changed public opinion and there's a lot less zeal for the drug war.

So all of those things have changed.

But at the time it was mass mental health was the goal, two tracks.

One was drug development.

The other was drug policy reform.

So then it's not just available to people to have a clinical diagnosis, but people who

are personal growth or, you know, they should have access to it as well.

I did not know at the time that no drug had ever been made into a medicine by a nonprofit.

That was really good.

I didn't know that.

It might have been a little bit more daunted.

And actually that didn't happen for 13 more years.

It happened in 1999.

And that was the abortion pill, RU46, that was approved in Europe, but it controversial.

No pharmaceutical company would take it.

And it was John D. Rockefeller III through the Population Council with the major donor

being Warren Buffett and the Rockefellers and the Buffetts and some of the Pritzkers

were involved in funding this.

So that was the first nonprofit.

But the maps was designed as from the very beginning, not academic research into psychedelics,

but drug development.

And that's a fundamental distinction.

And that's why I think we're years ahead now of everybody else in terms of making a psychedelic

assisted therapy into a medicine.

Because our goal from the very beginning was not knowledge, not academic research.

It was practical.

It was drug development.

How do we create new social structures?

How do we create legal access to these things?

Now in December of 2014, we created the Maps Public Benefit Corporation.

So Maps is a nonprofit, but in our 35 years, we've raised about $110 million in donations.

What I didn't know when I started Maps, and it took me quite a few years, I didn't even

know this till about eight, nine years ago, was that in 1984, Ronald Reagan had signed

a bill to create incentives for developing drugs that were off patent.

So MDMA was invented by Merck in 1912.

It's in the public domain.

These incentives are called data exclusivity, which means that if you make a drug into a

medicine that does no patent protection, nobody can use your data for a period of time to

market a generic, and that will effectively be, well, it's five years.

You do pediatric studies, you get six months extension, and we are being required if we

succeed in adults to work with adolescents with PTSD.

It blocks a generic competitor from applying for, until that five and a half years is over,

takes FDA at least six months to review.

So more or less six years of data exclusivity, 10 years in Europe is data exclusivity.

So the story then became to the donors that you're not going to have to give us money

forever because we can make money selling MDMA, but we want to do two revolutionary things,

you could say.

One is psychedelic assisted psychotherapy, but the other is marketing drugs.

When you market it with the profit maximization motive, we end up in the extreme getting the

distortions that we have in America, where we have the most expensive healthcare system

in the world per capita, but our outcomes are down like 40 or 50 among the countries,

our average outcomes.

We don't have third of the people or so don't have insurance, and it's just very inequitable.

So what we're trying to do is show a different way to market drugs, and it's a modification

of capitalism is called the benefit corporation, where you maximize public benefit, not profit.

You still make a profit.

So selling MDMA for a profit is not something we could keep inside the nonprofit because

it's taxable, it's a business.

So we've created the maps public benefit corporation, which is 100% owned by the nonprofit.

So we have a nonprofit that owns a pharma company.

And the mission of that pharma company is to maximize not profit but maximize benefit

for society.

Yeah.

Yeah.

Although there still will be profits and the profits that we're going to make are going

to be used towards the mission of maps, which is again, is this mass mental health and ending

the drug war.

And in fact, we've hired the Boston Consulting Group to help us plot our commercialization

strategy.

And so there is some suggestions based, there's so many different assumptions in this, the

number of therapists that we train, the price that we set for the MDMA, whether insurance

companies will cover it.

But there's the possibility of somewhere in the range of three quarters of a billion dollars

in profits during this period of data exclusivity, just from the US.

And we're talking about the, trying to do this research around the world as well.

So that's what the benefit corporation is.

The benefit corporation is our pharmaceutical arm.

We're about 130 people now, somewhere in that fluctuates, but a one third of them are in

the nonprofit.

We do harm reduction, psychedelic harm reduction.

We help create programs for people with difficult psychedelic experiences at Burning Man, at

festivals all over the world, even in cities.

We're now negotiating with the police, the city of Denver, because Denver has made the

mushrooms the lowest enforcement priority.

We organ is past the organ psilocybin initiative.

So in those areas where maybe more people are going to gravitate to do psychedelics,

we want there to be harm reduction so that we don't have bad stories coming out that

would change that.

So maps does the psychedelic harm reduction.

We do public education.

We do a lot of it.

That's what you and I are doing right now.

We're doing that now.

So but also research towards.

Well the research now is done in the benefit corp.

In the benefit corp.

Yeah.

So what happens is people donate to maps, get a tax deduction, maps transfers the money,

or you could say invests in the benefit corp.

The benefit corp will do the research and then maps is the sponsor, but then we will

license the sale of MD made to the benefit corp.

So.

Got it.

But the research are done with an eye towards creating something that has a big impact versus

just research for knowledge sake.

Yeah.

Yeah.

Because I'm interested in political change.

You can, the other part of it and which is that the brain is the most complex thing we

know in the, in the universe, it's going to, it's endless.

I mean, when are we going to really like this idea of will we figure out telepathy?

Will we figure out tapping into the clock of unconscious?

What is the extensive of our brain?

You know, how does the brain actually work?

Do you ask chemistry questions?

You know, so if it's just the pursuit of knowledge, that is an endless thing.

And how does that end the drug war?

How does that help people directly?

So that's why we're focused on drug development more than mechanism of action.

Before I ask you about one, but several really exciting studies, let me ask sort of a personal

question for me.

So if I wanted to get psychedelics from the Maps Public Benefit Corporation and explore

my own mind, how do I get to do that and when?

You won't be able to.

You'll never be able to.

This is very unfortunate.

But the reason is because the Benefit Corp is designed as a pharmaceutical company.

So we can only work on clinical indication.

So let's say you come to me and you just say, oh, I'm really depressed.

Can I get MDMA to overcome my depression or overcome my PTSD?

You know, we'll have to do research in those indications.

And by when you say me, you mean like a doctor.

So this would be prescribed in theory by doctors or this would go through a doctor and a prescription.

Okay.

Let me ask another question.

To further answer that.

So that's where the drug policy arm comes in, the drug policy reform.

So you should be able to get access to psychedelics for your own personal growth.

But that's not medicine.

So that's why we need to medicalize, to have things covered by insurance, to change people's

attitudes, the public attitudes.

And then we get this subsequent drug policy reform.

And we're talking about it in terms of licensed legalization.

So my view is you should get a license to do psychedelics, you get a little education

stuff and then you should be able to buy it and do it on your own.

So let me rephrase the question in more specifically.

So when can I, if I happen to have ailments of some kind where the doctor decides that

psychedelics could help?

When would you be a loose estimate for you of when a doctor will be able to prescribe

to me something from MAP's public benefit code, and then when for my personal growth

and creativity, would I be able to get something?

So like just looking out, this isn't like guaranteed, but like your vision, your hope

for, yeah, for psychedelics in society.

Well the end of 2023, so two and a half years from now, we anticipate FDA approval for the

prescription use of MDMA for PTSD.

Because the FDA does not regulate the practice of medicine, there is what's called off label

prescription.

What that means, the label is what it's approved for.

So the label says, this is approved for PTSD.

But let's say you come in anything else, social anxiety or whatever, you can go to the doctor,

they can give it to you, it might not be covered by insurance, they have to be a little bit

careful about malpractice.

But I think the end of 2023 is when you will be able to do that.

Now there's actually another program very limited called expanded access, which is compassionate

use, which means that, and we have approval for 50 people for compassionate use right

now, we think that'll grow.

So that's going to open up in about two months.

And so those are people with PTSD, they have to be treatment resistant, nothing has worked

for them, and they can access MDMA while we're doing the phase three studies.

But they have to pay for it themselves.

We're not the sponsor has to pay for all the research, but expanded access, because there's

no control group, everybody gets the MDMA, people can pay for it themselves.

And we think that'll start in a couple of months.

But it's very limited, it's limited to certain cities.

There's also a program called write to try, which is passed through Congress.

It's similar to this idea of compassionate use, but it cuts the FDA out of it and patients

can negotiate directly with pharma companies to get access to their drugs.

That's starting to happen, I think in Canada now they're letting people have compassionate

access to psilocybin for life threatening illness, because there has been studies with

psilocybin for cancer patients and others with life threatening illness.

As far as your question about when will you be able to access this for personal growth

outside of medicine?

I'll take that to mean fully legally, where you can just go buy pure drugs somewhere,

when will that happen?

We already are starting to see the decriminalization in certain areas of plants, psychedelics.

And we see overall drug decrym, like that passed in Oregon, so that any drug is now,

it's not legal, you can't really fully set up clinics to offer it to people or there's

no legal supply like that, but it's decriminalized.

So my sense of things is based a lot on watching what happened with medical marijuana and marijuana

legalization.

So we're sitting here in Massachusetts where marijuana is legal, but what happened first

was medical marijuana.

So what we see is that medicalization by demonstrating that under certain contexts,

the risks are much less than the benefits, and then there are benefits.

And then people hear stories about people that had gotten better, and then that changes

their minds, and then eventually that builds up to, why are we throwing people in jail

for this?

Because the culture, yeah.

Yeah.

So I think that what we're going to have 2023 is MDMA approved by the FDA, chances are.

psilocybin will be a year or two after that.

Then what we're going to need is a decade of psychedelic clinics that are going to roll

out across America, also other countries as well, thousands of these psychedelic clinics.

We already have hundreds of ketamine clinics that are a ketamine for depression.

More and more people are realizing that ketamine, when it's used with therapy, it's better

than when it's not.

But the therapists want to be psychedelic therapists.

They don't want to be a ketamine therapist or an MDMA therapist.

So those will be cross trained.

So we will have a decade of these thousands of psychedelic clinics and all these stories

of people getting better in 2035 is when I think that we will move to licensed legalization,

which is when you will have the option of just going somewhere.

Once you've done this educational stuff, potentially, I also think it would be better to have the

opportunity for people to go for free, paid for by tax money to these clinics.

And you have your first experience with psychedelics under supervision.

And you know what you're getting into, you've, you know, to ask the questionnaire what the

risks are with the drugs, then you get your license.

So 2035 is when I think that'll happen.

And the clinics will be sites of these initiations.

Yes.

And so it'll be a safe environment.

Just like you said, all the things that are actually maximize the likelihood of a pleasant

experience and all those kinds of things.

It is a frustratingly slow process.

And the FDA being part of that process is very frustrating that, of course, there's benefits,

but boy, well, I wish it could move a lot faster.

Yeah.

The thing that I've learned from being a parent is that when you have little kids, it seems

like they'll be with you forever.

But then when they grow up and they go to college and they leave, do you look back and

like, where did that 20 years go?

Yeah.

You know, so we're still dealing with the legacy of the civil war and slavery in America.

So actually a 20 year plan is not that long.

So while we say it's frustratingly slow, and it is, you know, I mean, it's 50 years

since the psychedelic 60s.

And, you know, right now it's, you know, it's 36 years since MDMA was criminalized.

And you think about all those people that committed suicide from PTSD or from anything

else, and all those people that could have been helped if the DEA had accepted the administrative

law judge recommendation at MDMA stay in schedule three.

It's tremendously sad.

At the same time, culture evolves slowly, you know, you read the Bible or you read all

this stuff, we're not that different from people thousands of years ago.

So how are we going to really evolve enough over the next couple of decades so we don't

destroy the planet and don't kill each other?

That's why I think psychedelics have an important role to play.

That's why I've devoted my life to psychedelics.

And it is frustratingly slow, and what I said to myself is our whole effort has not been

fast enough.

Can we talk a little bit about PTSD and MDMA?

There's this fascinating paper, came out on a fascinating study that you're a part of.

That's a phase three study.

Can you describe what the study is?

Can you describe what phase three means?

Can you describe what the findings are and why it's, in fact, so important and impact

for?

Yeah, this study came out May 10th in nature medicine, so one of the highest impact factors

in medicine, journals, it was tremendous.

So to make a drug and do a medicine, the first thing you need to do is what are called non

clinical or preclinical studies, meaning safety established in animals.

What does the drug do?

What are the side effects in animals?

Where do you see the risks?

And then you negotiate with FDA to do phase one studies.

And phase one studies are where you move from animals to humans, and those are more safety

studies and trying to describe what the drug does so that you can determine if there is

potential medical value there.

Certain drugs like cancer drugs are so toxic that you don't have phase one studies in healthy

volunteers.

That's like phase one slash two, where you bring in the patients, but you still are doing

sort of dose response safety studies, but you use patients.

But most phase one studies are healthy volunteers.

Phase two are where you start bringing in the patients and you start experimenting with

various different things.

The purpose of phase two is really just to design phase three.

Now again, I'm sort of putting out of the picture in another area is mechanism of action.

How do these drugs work?

Phase two, you're trying to figure out what they do, who your patient population is.

What are the risks?

Who do you include?

Who do you exclude?

What are the doses?

What is your treatment?

What are your measures?

In our case, it was how do you do a double blind study?

That was a big part of phase two.

That's a big challenge for psychedelic drugs.

Any kind of drugs that have a real strong effect, how do you do a double blind study?

Triple blind study to interrupt would mean that the patient should know, should not be

aware whether it's placebo or not.

And the research.

And the research is not aware.

And so for that lack of awareness, when the effect is really strong, it's very difficult

to do on both the research and the patient side.

Yes.

And sometimes they talk about triple blind.

So the other part is the raters that evaluate the symptoms and before and after.

So you ideally want triple blind.

You want the patients, the researchers and the evaluators of the outcomes and all of

them not to know what the drug, whether it was drug or placebo, and that's to reduce

experiment or bias.

So and then, then you move to phase three.

Once you've figured out how to design the phase three studies and phase three are the

large scaled multi site placebo controlled double blind studies where you must prove

safety and efficacy in order to get permission to market the drug.

Now for us, when we started maps in 86, as I said, it was one year after the criminalization

of MDMA in 85, we had five different protocols that were rejected by the FDA for studying

with MDMA.

And these were all various phase one studies.

They came from Harvard, from UC San Francisco, from the University of Arizona and Albuquerque

New Mexico all over, and they were all rejected 1992, six years after we started, we got the

first permission for phase one.

And that took us through much of the nineties.

Again, things are slow because we have to raise the money through donations.

And then in 1999 is when we started to work with PTSD.

And that then took us till November 29, 2016, which is when we had the end of phase two

meeting with FDA.

So it took 30 years from the start of maps to the end of phase two meeting with FDA.

And what we had discovered during phase two was several different key points.

The drugs that are available right now for PTSD, the SSRIs, Zoloft and Paxil, that have

been approved by FDA and regulators in Europe as well, the European Medicines Agency for

PTSD, they work better in women than in men, and they failed in combat related PTSD.

So what we learned is that MDMA assisted therapy works just as well in men or women, and it

works in combat related PTSD.

It works in regardless of the cause of PTSD.

We also discovered that even though there are stories that people take MDMA at raves

and they dance all night and they overheat and they get hypothermia and they die from

overheating, which is true and can happen from pure MDMA, or that sometimes people have

heard about needing to cool down and so they drink water and then while they're dancing

all night and then they drink too much water and then they dilute their blood and they

die from hyponitremia.

So there are risks of MDMA, but we discovered that in a therapeutic setting, we can control

all those risks, no thing don't happen at all.

So we discovered safety, we could demonstrate safety.

We also figured out that our measure, the CAHPS, the clinician administered PTSD scale,

that it's the gold standard all over the world for measuring PTSD symptoms.

It's what the FDA and the EMA require.

We discovered that it was a good measure for us and that we could show changes in that.

The other big thing that we learned is that, and we haven't mentioned this yet, but the

work in the 50s and 60s with LSD and psilocybin and the modern research over the last 20 years

with psilocybin and classic psychedelics has demonstrated that there's a link between

this mystical experience, this unit of mystical experience and therapeutic outcomes for the

treatment of addiction, for working with people's life threatening illnesses, for OCD, for obsessive

compulsive disorder, that there's with the classic psychedelics, both in the 50 years

ago and then the research now has been that there's a link between the depth of the mystical

experience and therapeutic outcome.

What we discovered is that that's not the case for MDMA, that people do score fairly

high on the scales of mystical experience, not as high as they do with the classic psychedelics,

but they do score pretty high on average and a significant number of them have over the

cutoff for what would be considered a full mystical experience.

So enough to say that we could look at a correlation and we didn't find any.

The other thing that we discovered, and this was more humbling, I would say for me personally,

is that my dissertation at the Kennedy School, a big part of it was on the regulation of

the medical use of psychedelics in marijuana.

Big part of my dissertation was how to do the double blind study and I thought I'd solve

the problem and I persuaded my dissertation committee that I'd solve the problem and the

solution was therapy with low dose MDMA versus therapy with full dose MDMA and everybody

knows that they're going to get MDMA, most of these people have never done it before,

they'll be confused about is it full dose or low dose and then the challenge is to pick

a dose that's high enough so that there is this confusion, but not so high that it's

so therapeutic that we can't tell the difference between the groups.

So we studied zero, meaning inactive placebo, 25 milligrams, 30 milligrams, 40 milligrams,

50 milligrams, 75 milligrams, 100 milligrams, 125 and 150.

What we discovered is that my dissertation was wrong and that there is no good solution

to the double blind problem.

What we found is that, two hour surprise actually, was that 75 milligrams was an effective dose.

We didn't think that, I mean, the normal dose is like, full dose is like 125 milligrams,

something like that, but 75 milligrams was an effective dose and we discovered that the

lower doses, so I was half right, you could say, the doses of 25, 30, 40, 50, they could

produce enough confusion that you could say that they were successful at blinding, not

perfectly, but enough confusion so that people, therapists couldn't know for sure so that

there was this reduction of bias, you could say.

But what we discovered, again, to our surprise, was that the low doses made people uncomfortable.

They stimulated them, but they didn't reduce the fear and so people still got better with

the therapy with low dose MDMA, but if we gave them therapy with inactive placebo, they

did even better than if we gave them therapy with low dose MDMA.

So we call it an anti therapeutic effect, I don't mean to imply that they got worse,

but it made people uncomfortable, people didn't like it, but we would still help them make

some progress.

So we had the blinding, but what it meant by reducing the effect of therapy with inactive

placebo is that it would make it easier for us to find a difference between the two groups.

And so the real question is, if you can do it with therapy, why bother add a drug?

So we went to the FDA and so this was what we discovered during phase two.

We went to the FDA at this end of phase two meeting and we said, we can give you blinding,

but it will make it easier for us to find a difference between the two groups.

And so we suggest that we do therapy with inactive placebo versus therapy with full

dose MDMA.

That will cause a problem because most people will be able to tell what they've got.

But Tom Lawfarin, a doctor who used to be head of psychiatry products at FDA is our

main advisor.

So the first thing he said is that the double blind fails in practice a lot, even with SSRIs

because there's certain side effects that you have with these drugs and the doctors

who are doing these research when you're reporting your side effects, they can say, oh, that's

probably you got the active drug instead of the placebo.

So the double blind is in theory is terrific, but in practice, it doesn't always work quite

as well.

And so what Tom said is that there are two main approaches that they think are important

to reduce bias.

The first one is easy to do.

It's called random assignment.

So sometimes there are studies where you'll treat a bunch of people with something and

some fraction of them will get better and some won't.

And then you say, okay, all those who didn't get better, who volunteers to get this new

treatment?

And then you give them the new treatment.

But the people that volunteer are more likely to want to get better.

They're not representative sample of everybody that has the disease.

So when you have random assignment, everybody is similarly motivated and has meets the same

inclusion exclusion criteria.

So that's what we told, of course, we need random assignment.

The other part was when the bias double blind doesn't work as well, then the system of independent

raters is especially important of how you do that.

So we have over a pool of raters, over 20 of them, and we do this monthly interrater

reliability tests to make sure that they, you know, evaluate this so that they're given

a videotape of a PTSD patient and then they're supposed to rate them according to their

symptoms.

And then we sort of make sure that we've got this calibrated raider pool.

And it's all done by Zoom, by telemedicine, and they're randomly assigned to the next

person that needs a rating.

So you said 20 raters.

Yeah.

So we've got like 20 raters.

And what we want to do is make it so that each raider sees each patient only once, maybe

twice, but not tracking them through the study.

So that guides to reduce the bias in the raters, that they don't know where this person is

in the study.

And so there's a fellow, Bob Temple, who's like the old wise man at the FDA, he's been

there since 1972.

He was in charge of the Office of Science Policy and they brought him into the final

meeting of this process where we are trying to design phase three.

So once FDA said, yes, you can go to phase three, that was November 29th, 2016, we then

negotiated for eight months on the design of phase three and all of the other information

is just fascinating is going to need this process of design.

Oh, it was, you know, to the extent that I have any artistic creativity, it's in protocol

design.

I really love that.

You enjoy this process.

I love it.

I love it because it's always tradeoffs and it's, um, yeah, it's, you know, and then

I acknowledge, you know, that, that we are all biased and so how do you, there's something

beautiful about the scientific process designed to get you to the truth, um, especially when

that scientific process is trying to get to the truth of the human organism, which is

so complicated.

So it's very difficult to, uh, to dissect, to, to, to get the, the, the strong effects.

And when you're analyzing, when you have like raters, they're, they're watching a video.

So just removing subjectivity from that is very, very challenging.

Yeah.

Very, very much so.

And so we came to this agreement with FDA though, that, that we would, um, use this,

uh, independent radar pool and, um, and so we learned in phase two again that the double

blind, there was no solution to the double blind problem and, and both the FDA and the

European medicines agency in the end agreed that the best design was therapy with inactive

placebo versus therapy with full dose MDMA, accepting the fact that most people will be

able to tell what, whether they got nothing or they got full dose MDMA.

Most therapists will be able to tell the difference, but, um, that makes a harder test for us to

show a difference between the two groups because we're giving them inactive placebo and not

the anti therapeutic effect of low dose MDMA.

So once we started phase three, so then we were able to start, um, in 2018 phase three

and the paper in nature medicine that just came out was the results of our first phase

three study.

We came to agreement with FDA that we would do two phase three studies.

Each would have 100 persons in them.

And what the FDA said to us is that they thought that we could prove efficacy with smaller numbers

than they wanted to see for safety.

The reason they said that is it in phase two, we had a large effect size.

So from a statistical point of view, the bigger of an effect that you're looking for, the

fewer number of people you need to get statistical significance.

When you're trying to find small differences, you need large numbers of people to sort of

work out the noise.

Um, so we were, we came to agreement on two 100 person phase three studies.

And the idea is that it's very possible that the, the first part, the first study would

show the efficacy because the effect is so strong.

Yeah.

Yeah.

And the second, but, but also safety as well.

So, so, you know, one of the things we also realized when you work with a highly stigmatized

drug in the midst of still, you know, the drug war and prohibition that we need to highly

sympathetic subjects and we need to make the best case we can, which means we need to work

with the hardest cases so that this is really needed.

And so we end up enrolling people.

The first study was chronic severe PTSD.

And unlike many studies of PTSD, we enroll people that have previously attempted suicide.

So we have multiple people that have tried to kill themselves that we felt like, um,

if we were to exclude them, what are we doing that?

Those are the people that need it the most.

So we came to this agreement with FDA, we're going to work with chronic severe PTSD patients,

including those that attempted suicide.

And we would do these two 100 person studies.

And we also negotiated what's called an interim analysis.

So what that means is that when the study is underway and often big, big studies, they

have this kind of interim analysis where what you do is, and for us, we negotiate when we

had 60% or 60 people had reached the primary outcome measure and all hundred had been enrolled.

Then we would take a look at the data.

And if the statistical analysis that we did was, um, showing, you know, based on a certain

effect size that we chose based on what we saw in phase two, the interim analysis is

for what's called sample size re estimation.

So what it means is if the results aren't as good as you thought they would, you can

add more people and then you'll get statistical significance.

It means that your effect isn't as strong as you thought it'll be harder to get insurance

to cover it, but FDA will still approve it because FDA also believes that these are group

averages.

There may be some people that will later figure out, respond better than others.

So they'll approve it if it's statistically significant, even if it has a low effect size.

The SSRIs have low effect size.

So we did the, um, interim analysis in March of 2020.

And what we discovered to our delight was that, um, we did not need to add any subjects.

That's all we were told.

We weren't told like, what is the results?

We were just told all we were going to get is a number zero or you need to add X numbers

of people to the study to get statistical significance.

That's right around the time that COVID hit and lockdowns happened and we ended up negotiating

with FDA that we would end the study with 90 people instead of a hundred.

It took a while for us to end up doing that.

So the paper that we just published is on the results of 90 people.

I think it was 46 in the MDMA group, 44 in the placebo group.

And what we discovered was that the study worked better than we had even hoped.

So the first thing is that you look at statistical significance, you have to get.05, which basically

means a nickel out of a dollar, one in 20 chance that the difference between the two

groups is due to some random factor rather than to your intervention.

And in this case, the, the placebo group gets therapy and then with inactive placebo and

then the group gets MDMA with active placebo.

So you have to get.05.

There's another measure that the FDA uses sometimes called robust, which means one in