Original subtitles

-It's amazing.

It's really amazing.

This is the structure of LSD that we published

with the 5-HT2B receptor. Oop.

There's LSD. -Oh, wow.

-So you dropped acid. That's like...

How does that little tiny thing

stabilize the active state of the receptor

and then have all these effects on human consciousness?

So we just got this structure. This is brand-new.

No one in the world has ever seen this outside my lab.

This is the holy grail of hallucinogen action right here.

We have caught the hallucinogen in this stage

of activating the receptor at atomic resolution.

-Is this the first crystal structure --

-This is a cyro-EM structure, the very first.

Yes. The only, as far as I know.

-5-HT2A is the most important receptor

in the action of serotonergic psychedelics,

but its precise confirmation

in the presence of an agonist like LSD

has eluded scientists for decades.

For the first time,

the structure of the LSD-bound 5-HT2A receptor

has been elucidated using cryogenic electron microscopy

and X-ray crystallography.

With the target now known, thousands of new psychedelics

can be designed from the bottom up,

ushering in a new era of psychedelic research.

I've been fascinated by psychoactive drugs

my whole life.

I love to study their chemistry and impact on society,

and my work has allowed me to investigate

extraordinary substances around the world.

Yet there are still mysteries that remain.

-When I grew up, it was very isolated.

I left school at 16 because the nuns wouldn't

give me books about Buddhism, so I studied that.

I studied classical Arabic.

Art was always my thing.

Then I had turned on to cannabis when I was 16,

LSD when I was 22.

And then when I was 23,

I had a life change

in as much of the trauma and then a love affair.

And the love affair came with the added advantage

of immensely important new knowledge.

And it was knowledge which enabled me to practice

how to live at that level of consciousness

that I had always aspired to.

-A full draw?

-I do only a full draw.

The tragedy of Prohibition

was that people stopped talking about LSD.

I felt this is just a mistake society's making,

and so I thought, we have to first change drug policy

and get it based on scientific evidence,

because without that,

one's not gonna be allowed to do the research.

I'll do it through the best science.

So that was my intention at the beginning of the '70s.

My thing is to put it on my hand and lick it,

but if you prefer to put it on a bit of paper,

you can divide it in two.

-I see. That's an interesting technique.

-The research that we are now doing is showing,

amazingly, how psychedelics in this case LSD,

increases the connectivity, increases the function, etc.

It does help one thing.

If you don't feel it let me know

oh ok

-How do these things change our very basic consciousness?

-People have attempted to understand

and study consciousness through art,

through writing novels, through music,

through philosophy,

through all sorts of different processes.

Why use science as a way of studying consciousness?

-Well, my -- my natural way would be the other ways.

I mean, altered states of consciousness,

extraordinary experiences,

are very fascinating study,

but they're very difficult to study.

I mean, I know telepathy exists because I had this passionate

love affair with a pigeon who I brought up from a baby,

and he fixated and fell madly in love with me

and I with him.

That was the beginning of one of the most

meaningful relationships in my life.

He had two main emotions,

which was passionate love and hateful jealousy.

He hastened my partner to the room every day

and then came back and settled the conquest in the bed,

and his whole thing was getting me to passionately cuddle him.

And he was hypnotic. You know, he had a call

which you actually couldn't resist.

Mm. Mm. Mm.

And this would go on and on and raising, rising around.

And then finally, you find yourself unable not to go

and have a cuddle for half an hour.

Very hot air.

And he'd kiss my pupils.

Incredibly delicate little, tiny kisses.

Love-making. Sweet.

And it's just enchanting how he'd do it with the sound.

It was a very kind of complete love.

And he'd always be somewhere swooping off.

It's a great bird adrenaline,

and he could never make out why I didn't go with him.

Pathetic, cripple -- human cripple who couldn't fly.

My life would have been very different without Birdie

'cause I would have done all sorts of things

like marry Bart, but I never did

'cause Birdie wouldn't have liked me moving to Holland,

'cause one couldn't take Birdie to Holland.

Then he could never go out.

I learned the sound through Bart, Bart Huges.

He made LSD in his mother's kitchen,

and she threw it away and they had to make it all again.

And that was LSD which turned on Europe,

and it got to me in London.

And then I -- I took it and really thought,

"This is amazing."

Through meeting that scientist of great genius

and a long and marvelously productive love affair with him

that then enabled myself to get high

and work with LSD.

It's a natural product. It's made from ergot,

which is the mold on rye, which the witches

used to collect to make their magic brew.

-There's a fungus. It's like the mold that grows on bread,

only this fungus grows on wheat and it grows on rye.

And one of the byproducts of this fungus

is a group of chemical compounds

made up of several different chemical constituents.

And all of these constituents

have a powerful effect on the body.

And these effects vary all over the map, from everything

from causing an abortion to curing a migraine headache.

Now, any time you have a naturally occurring compound

that has powerful physiologic effects,

the people in the drug industry, drug researchers,

will be looking at these molecules.

They'll be trying to modify them, to change them,

to see if they can change the effects that are produced

to make them safer.

They look for a lot of things.

-Disc sclerotium is one of many stages

in the life cycle of ergot,

a parasitic fungus that infects grasses around the world.

it will eventually fall to the ground over winter.

And in the spring, ascospores will infect

future fields of grain.

The alkaloids contained within ergot

can be used to synthesize a variety of psychedelics,

chief among them, LSD.

Given how fluorescent these lysergamides are,

I assumed that I'd be able to visualize them

with an ultraviolet light.

But they didn't fluoresce at all.

-Correct, yeah, the ergot sclerotia are like

little pebbles.

You cannot see the fluorescence from the outside.

You have to extract the alkaloids.

There are all kinds of pigments that have evolved

presumably to protect the ergot alkaloids

from ultraviolet light.

I was always interested in the idea of microorganisms

that we cannot see very well and that chemicals

that those microorganisms produce can affect us

on a societal level.

-When you say affect us on a societal level,

are you referring to LSD?

-That chemical has certainly had a profound effect on --

on our society.

All the other good alkaloid pathways start the same

through the first four steps that we know of.

The critical branch point

is that chanoclavine aldehyde.

Without the double bond,

they're dihydro ergot alkaloid producers.

With a double bond,

they're lysergic acid derivative producers.

-And this has been the major effort of your career

is to figure this out.

-Yes, figuring out the steps in the pathway

and then also trying to understand biological function

of these alkaloids.

-The alkaloids that are hydrolyzed

to produce lysergic acid are extremely difficult

to synthesize, and without ergot,

LSD would have probably never been discovered.

So how does the fungus accomplish what is so difficult

for human chemists?

-Fungi are pretty amazing in terms of the chemistry

they can conduct, and you can find all kinds

of unknown biosynthetic pathways in a fungus genetically

that have never been found chemically yet,

and there are things you can do to wake the fungus up

to make them produce chemicals.

One interesting example is the fungus that is used

in making Brie and Camembert cheeses,

Penicillium camemberti.

We were surprised to find all the genes required

to make an ergot alkaloid. -Oh, wow.

-That fungus was domesticated

really in the last couple of hundred years

from another wild Penicillium species,

and that wild Penicillium species

still produces the ergot alkaloid.

-Wow. And do you think it could be induced?

Could you produce a Camembert

that contains psychedelic lysergamides?

-It would take some genetic engineering,

but it wouldn't be that difficult.

-Why do you think the fungus would choose this sort of host?

What benefit would it have? -Yeah.

Well, I mean, the fungus has the benefit

of a relatively competition-free source

of high-quality carbon.

In return, the fungus is providing protection

from herbivores.

If we inject it in insects, it will kill the insects.

If we remove the ergot alkaloids,

the fungus can no longer kill the insect.

-Do you think they enjoy the effect?

-They hate it.

When they're dying, they either just quit trying,

or they'll squirm in a circle,

writhe uncontrollably.

-You don't think they're writhing in joy?

-No, I highly doubt that.

-It seems like just an amazing compound

from a drug-design standpoint.

It's almost like it was built perfectly for that receptor.

You couldn't ask for a better fit.

And there's something really miraculous about that.

The incredible potency of some lysergamides,

or other fungal alkaloids like psilocybin,

tends to promote this sort of misconception

that these things must have been made for us

because they have such dramatic effects in the human mind.

But that's almost certainly not the case.

-Correct. It's hard to come up with

an argument or a case where intoxicating humans

was in some way beneficial to a fungus.

Fungi themselves -- they're out there competing

with insects and other fungi

and other bacteria for resources.

I would say that the ergot alkaloids

are most likely originated

as ways of deterring or killing insects.

We share neurotransmitters with insects.

Therefore, we are affected

by the same chemicals in different ways.

-While a diverse array of fungi produce ergolines

for defense against insects,

humans have also been victims of ergot poisoning

for most of recorded history.

High doses of contaminated rye

led to instances of gangrenous ergotism and death.

-It's a matter of dosage.

In the cases where people suffered from ergotism,

they were on a diet that was primarily rye bread.

And if the amount of ergot to grain was greater that 1%,

then they could suffer these symptoms.

With a diversified diet,

people are unlikely to suffer these things.

-Do you think that there's a reason that

LSD-type lysergamides never appear in nature?

-Um, I'm gonna guess in an ecological setting,

they provided no advantage to the producing fungus.

-The ergoline scaffold is found in

so many different forms of life.

Why would it appear in a sea squirt

and the morning glory endophyte

and a entomopathogenic fungus

and the fungus that infects grasses?

-In many cases where we see chemicals

that we associate with fungi otherwise

and then we suddenly see it pop up in an animal or a plant,

when people look hard enough, they find a symbiotic fungus

that is the real source of the chemical.

Serotonin receptors, dopamine receptors

are common to lots of animals.

The ergot alkaloids interact with those receptors

and produce an effect that provides an advantage

to the producing organism.

-This is a beautiful topiary.

It almost looks like the spore-elating structure

on an ergot sclerotium.

-Ah!

It it does, I don't see that.

-I think the freedom to explore your own consciousness

is your personal right,

whether they call it a U crystal or medicine...

...or just something to make them see more beauty.

You're cheating beauty if you go and see it in a way

without enhancing your potential to see beauty.

My partner, Bart Huges,

I think in an experiment at the university, took LSD,

and he thought, "This is very incredible,"

and started thinking about

what is a physiological underpinning of his state?

And so that was -- had always been my passion,

but it became more so, and it got a new grounding

with the hypothesis about the fall of man,

the fall of blood from the brain with the upright position.

-Wow. I've been wanting to read these for a really long time.

-Have you? -Yes.

They're impossible to find. -Ah, yeah.

He saw a friend of his stand on his head at a party.

And he said, "Why are you doing that?"

And he said, "To get more blood in my brain."

And then he suddenly realized because blood is heavier

than cerebrospinal fluid, pushes it down.

It's to do with gravity.

The upright position came

with a sudden loss of blood from the brain capillaries

so there was less brain function,

simultaneous activity.

By creating an expansion window in this closed system,

the skull, the blood blows up to a different level.

The pressure of the heartbeat results in a higher volume

of blood in the brain capillaries.

-So amazing.

-He was very brilliant.

Bart got run out of England

and wasn't allowed to get back in,

although he'd never committed a crime in his life.

His only trying to say that LSD is a very --

some journalist interviewed him and he's said --

I can't remember what he said.

He said, "It's an extremely interesting compound

you should research," or something.

And he called his daughter Marijuana.

-He named his daughter Marijuana?

-Yeah. And that was enough to get him exterminated

from the English borders for the next 20 years.

-And was the trepanation also controversial at that time?

-Eh, it wasn't a crime.

You couldn't really use drugs, and they were much more taboo

than trepanation, funnily enough.

Interestingly, trepanation has been done

throughout the world independently.

Whether it was in Peru or Tibet, it was a very accepted thing,

and now it's not accepted, just as psychedelics

were impossible to research for 20 or 30 years.

Now I'm finding trepanation impossible to research

because it's really difficult to get ethical approval.

It's so easy to do the research into trepanation.

It is mad that it's not done. I mean, that's the crazy thing.

I -- I've got plenty of people who'd volunteer to be trepanned.

-Was there any interaction between trepanation and LSD?

For example, did LSD feel different after trepanation

than it did before?

-Yes, I would say there was.

Taking a psychedelic like LSD

is a big shift to the system.

I think the cultures where you find trepanation

were cultures where they used to take psychoactive substances.

And I think people who were trepanned

were often the priest caste.

You can see that they were the people with special burials.

And the priest castes were the castes

who took the psychoactive substances.

So I think they were related.

I think they're in the same spectrum.

-I love the brain.

I -- I've always been fascinated by consciousness.

I set up the Beckley/Imperial Research Program

to study psychedelics with Dave Nutt.

We did the first study with psilocybin,

which showed it could treat depression,

and the first brain-imaging study with LSD,

and now the first brain-imaging study with DMT,

and a lot of interesting studies.

-I was able to make MDMA for Rick Doblin,

and I made...DMT,

and I made the psilocybin for the Johns Hopkins studies.

The substances were not available.

Nobody would make them.

They were prohibitively expensive.

None of this would have been happening.

I feel really privileged because I was able to enable

what's now being called this renaissance.

It's pretty, huh?

-Amazing.

-This is the normal lysergamide,

and this is the iso that follows it.

Some that are -- see if I can cut that a little bit,

get a good clean sample of the first one out.

So now it's just a waiting game.

Cool thing about working with lysergamides

is if you spill it -- see my glover there?

-Ha!

Once one of the only chemists in the United States

licensed to produce LSD, Nichols is now retired

but continues to synthesize psychedelics at UNC Chapel Hill.

His illustrious career,

spanning the synthesis of hundreds of novel compounds,

is now winding down with one final creation --

a nitrogen mustard derivative of nor-LSD

he calls CELAD.

Is there any compound that you've

wanted to synthesize that you just couldn't

figure out a way to do it?

-Well, for a long time it was this one.

-Nichols' psychedelic nitrogen mustard

would form an electrophilic aziridinium ion

that he hopes would alkalaid a mutant 5-HT2A receptor,

forming an irreversible bond

that could facilitate study of the drug receptor complex.

It seems like these lysergamides are pretty close to perfect.

Do you think there's a lot of room for improvement?

-If the duration of action and the potency is related

to being trapped in the receptor,

you might be able to get high-potency ligands

that didn't get trapped,

that wouldn't have such a long duration of action,

and they might be more useful for therapy.

-Right. -It's an interesting time

'cause there are a lot of players are getting

into the field now... -Yeah.

-...including some big-pharma people trying to see

how they can make money.

-It happened so quickly. -Yeah.

But I spent my whole life in this field

and never thought we'd get to the point we are now

in my lifetime.

All of a sudden, it's, "Oh, these things really work."

Now they have medical potential.

I don't think it's gonna be that straightforward,

but there are opportunists jumping in,

and that's kind of surprised me.

-David Nichols has synthesized more psychedelic compounds

than almost any other chemist in history,

maybe the most.

He's made enormous contributions

to the pharmacological understanding

of how psychedelics act in the brain.

And he's a real legend among anyone who cares

about the science surrounding psychedelics.

Okay?

Nothing fantastic.

I don't make any money playing the flute.

That was great.

In high school, I was kind of the chemistry geek.

I figured out how to make an improved stink bomb

that wasn't dangerous and things like that.

-Was it? -Well, you know,

the classic stink bomb was iron sulfide and acid,

and I didn't want to carry a bottle of acid around.

I thought that was a little dangerous.

So then I eventually came to discover

that aluminum sulfide was reactive enough,

that water was acidic enough to generate hydrogen sulfide.

So if you were in that room, you start going,

"What's that smell?"

So, you know, stuff like that.

It was things you can't do today.

I mean, at that time, you could go in there and buy saltpeter

and powdered charcoal and sulfur and make gunpowder,

and the pharmacists would just wink at you.

Cincinnati is a very conservative place.

All the things that were happening on the West Coast

were not happening in Cincinnati.

And they actually had a street that was full of hippie shops,

and the police went up

and they just declared them all fire hazards

and shut them all down and got them out of there.

They didn't want any kind of hippie influence in Cincinnati.

Not that I was a hippie, because my parents

were really conservative.

I think my father had PTSD.

Spare the rod and spoil the child.

So I developed an anti-authoritarian attitude

from a rebellion against my father.

Some friends in high school started smoking reefer.

"Smoking what?" "Reefer, marijuana, man."

"Oh, you guys are gonna get addicted."

And they start laughing at me.

So I went to a bookstore in Cincinnati,

a used bookstore and I still have the book.

It's called Sollmann's "Manual of Pharmacology."

And I read the chapter in there that talked about cannabis,

said, "There's nothing to it.

It's not addictive. It's harmless."

I said, "Well, this is not what I'm hearing

on the radio all the time."

So I was like their consultant, I guess, on all things drugs.

So then I thought, "Well, you know, this is cool.

I should go to school and learn about these more."

-I know that it's controversial to talk about

personal experience, but I also know that

this is something that has informed your research.

Are there personal experiences that you would want to share

that might illuminate some of this?

-I did have an experience early on where I closed my eyes,

and I was projected outside the universe.

And the universe was so far away,

it was just a dim green glow off in the distance.

And I still remember that. It was very powerful.

I said, "Oh." And the whole purpose

of the universe was to bring forth life.

I suppose if you could set up a society an ideal way

and had kind of a rite of passage,

which is what, like, a lot of primitive societies do,

and they put them through some pretty grueling things

sometimes to wipe out

all the abuse they've gotten as children,

I think a lot of people could probably benefit

from a psychedelic experience some time in their lives.

It seems to me like there's a yearning among the public

for something different.

I never expected that all this medical stuff

would be taking off like it is.

Ultimately, the goal of all these people,

even if it's unwritten, is to understand who we are.

And psychedelics get us closer to that

than almost any other thing I know of.

-You mentioned when you were first

getting interested in this,

that you read publications by Alexander Shulgin.

Did you reach out to him at that point,

or when did you start to really wonder who this guy was?

-I met him when I was still a graduate student.

We had a nice, lively discussion.

As an academic, I had to have hypotheses to test,

but Sasha could just say, you know, like, "What if?"

"What if we make this? What if we make that?"

And then he would take it himself, and he would find out.

So people said, "Oh, he was a scientist.

And I said, "No, he wasn't really a scientist.

He was an alchemist."

He really was an alchemist.

A scientist has to test a hypothesis.

You refine it. You develop a theory, you know.

He didn't do that.

I don't think he had any goal other than just to see

how many kinds of things he could make.

And he was always looking for -- you know,

he was always interested in drugs

that would enhance human communication.

Sasha said, "I communicate with anybody that writes to me.

Don't worry about it."

So I just wrote him a letter,

and I've got two boxes of correspondence --

letters that I had with, to, and from Sasha.

August 24th, 1970.

"Dear Mr. Nichols,

Thank you for your kind letter of August 11.

I have no idea if it's proper or considerate

for a graduate student to correspond

in addition, in extenso, to his mentor.

But I assure you, I am not in any way swayed

by conventions and proprieties."

That's fairly.

"I am exclusively interested in scientific information

and appreciate any correspondence

that will allow me to give and take in the area

of new ideas and observations.

-Wow. "The world is ripe to learn

but jaded to be instructed.

The psychotomimetic thing will not be solved

in the next three months, and don't knock yourself out

in the effort.

Learn your trade, the degree,

then learn your art, the skills within your fingers,

and only then begin to build upon the insights

that may result from the knowledge

that these separate threads can be tied together.

This letter has become unchemical.

Take care."

-Oh, wow.

Oh, he's such an amazing person.

Did he send you drafts of sections of "PIHKAL"?

-Oh, I saw the whole manuscript.

I said, like, "I don't think anybody wants to know

about your sexual habits with Ann."

And he said, "Yeah, a lot of people mention that."

So they took a lot of that out, or most of it out.

-There's still a good bit in there.

-She took the opportunity to really express herself,

shall we say.

It was pretty -- pretty racy before.

-It remained very racy.

What evolutionary or biological reason

would there be for such an effect to exist,

a psychedelic effect?

-I don't know that we evolved to have that happen.

But if you look at where this 2A receptor is expressed,

it's on the cortical pyramidal cells,

which are the major computational units

in the brain.

So all your subcortical stuff, all your unconscious stuff,

your imagination, your memories, everything -- that is all input

into these cortical cells, which is processed.

You know, it's something about the way the brain is structured.

The 2A receptor is really an ancient receptor.

Serotonin 2 receptors go back into single-celled organisms.

Nature found something that worked really well,

so it kept it all the way up through the evolutionary chain.

The doses that produce these psychedelic effects

are probably way higher

than anything that would normally occur in the brain.

And so you're really over-driving.

You're really turning on these receptors

to a level that they wouldn't normally work.

And then you're shutting down the filtering mechanisms

that normally keep a lot of subcortical stuff

from getting into the cortex,

kind of like the on/off switch on your TV set.

-We enhanced our consciousness with LSD

in order to further explore intuition

and the flow state and the mystical experience.

Whatever -- taking our acid and going for a walk around the park

and deciding, how do you solve the crisis of the ego?

That was our day.

We used it just very largely to think better.

-Think it's your move. -Okay, so playing.

Okay, so let's start. Enjoy.

-And a very good test of one's thinking

was paying "Go."

If I was high on LSD with the right sugar level,

suddenly you'd see things,

and you just note, "That's the next move."

You didn't have to think about it.

It was just intuitive.

-A little bit greedy, but hope springs eternal.

-All right, here we go.

-Ooh, the [mumbles], ooh.

It's very close to being a good -- very good move.

So I'm a little bit nervous.

-No, it makes one move away from being a disaster

is what I -- is what I mean by that.

It's well known that people are worried

about the use of drugs as -- as formed enhancers in chess.

But there's been some discussion of that in "Go" playing,

and all the sort of thoughtful evidence is,

in "Go" playing, nothing makes you play better.

-"Go" is more intuitive. -I think so, yeah.

-Pattern recognition. -Indeed.

One of the things I used to feel about

a lot of strong "Go" players -- they write these books.

"Why am I such a brilliant 'Go' player?

Buy my book. You'll understand." Right?

Of course, they couldn't tell you the whole truth

'cause they couldn't actually say what was really going on.

It's a bit like saying, "What's it like to --

to feel that you're in love?"

If you try to explain that someone who's never been

in love at all, they haven't got a clue.

And if you try to explain it to someone else who's been in love,

you'll probably find their idea of being in love

and yours are not the same anyway.

But they've got a glimmering.

It's that sort of feeling with all of our thinking.

I think it's two things that have no business being together

are brought together and, zing, something magical comes about.

All of this stuff is happening in a non-verbal domain.

-If I had hypothetically taken LSD,

I might say that the amount I took is just right,

just the right amount of LSD.

Any more would have been too much,

and less would have been not enough.

-That -- that was our room in where I still live.

This was a tiny, little room which very often

had about a great many people in it.

And that's me and that's Bart about that period.

Ah, this rather clever and not attractive character

who turned Leary, funny enough, onto LSD,

called Michael Hollingshead -- he was hanging around my flat.

He had a bottle of LSD, which he got from Sandoz.

It was famous for its size.

And he poured it into my coffee.

So I had as bad an experience

as more or less one can have.

-Why would he do that to you? -What?

-Why would Hollingshead do that to you?

-To take advantage of me. -Oh, God.

-Yeah.

-Jesus. -Yeah.

And so that was very damaging. But that's life.

And, I mean, life comes with all sorts of traumas.

And so that slightly frightened me off LSD.

And I came back here, actually, and lived in a hut

beyond the orchard for months.

Then a very nice friend came by and said, "You must come.

There's a party in London. Ravi Shankar's playing.

Ah-da, da-da, da-da. Fun, fun, fun.

What are you doing?"

So then I went, and there I met Bart,

and then we started a love affair.

It was obvious we were going to be...partner.

-Why didn't he continue working with less-invasive techniques

for altering blood flow to the brain,

like standing on your head

or even laying down in a bed or...

-Um, standing on your head needs a lot of muscular control

and discipline and all those sort of things.

And, well, trepanation is not easier.

No, I agree. -You made this amazing film,

"Heartbeat in the Brain," but you wanted to wait

until you had some scientific validation of --

-Ideally, that's what I would do.

-Yeah. -I'll tell you,

I only did it actually for -- at the end --

for intellectual curiosity,

in the sense that it's a very fascinating hypothesis.

I haven't seen the film for 10 years or shown it to anyone.

I'm not good at machines.

-I can figure it out probably.

-I want to make sure we edit...

the kind of bloody bits.

-Okay, that's not a problem. -Do you see what I mean?

-I feel... -I do. I understand,

I understand. -...I don't know.

-I will say that it's going to be difficult

to present it in a way that a certain type of person

won't be shocked by it.

-Yeah, I don't want to kind of upset the boat.

-I understand.

-'Cause I've got all the LSD research I want to do.

I've got all the 5-MeO research.

You know, I've got several big projects, a clinic, and a lab,

all of which I'm trying to get going.

So I don't want to kind of go and blurt out, da-da-da,

anything I've got cheated with.

-Okay, is there any introductory thing

that you think should be said?

-Um, just that I'm absolutely not in favor

of self-trepanation.

It's absolutely not a thing for laypeople to do.

Maybe better to say it's a film about my beloved Bart.

It is me looking rather anxious.

It's the morning of the operation.

Here's Birdie, who lives with us.

This is an old skull,

an Irishman, I believe, in his day,

which I practiced drilling on.

I decided to make the hole in the median line

just above the hairline.

Here, I'm lifting the instrument

out of the sterilizing fluid.

This is the bathcap I wore to keep my hair out of the way,

the dark glasses I wore

to keep the blood from trickling into my eyes.

I taped them to my forehead.

They had the effect of depersonalizing me.

This gets a bit gory. I think it should be...

This is the electric drill

with a flexible drive.

I stop drilling...

to dip the drill head into distilled water

to cool it.

There are three layers of bone to get through.

What we are doing in trepanation

is removing a piece of bone from the skull

and is not entering the brain.

The brain is soft like a pudding.

It became like...

I think now maybe one cuts.

There was absolutely no pain.

A local anesthetic saw to that.

I mean... -Pretty amazing.

I -- I really just love this. I think it's so amazing.

-I -- I rather love it, too, you know.

-It's -- it is a masterpiece. It's truly a masterpiece.

-You think so? -Absolutely.

-Really? It was well thought out.

But, you know, it looks a little mad.

-I think, if anything, this has the opposite effect.

My thought is not this woman is mad,

but this woman is an artist and this woman is very brave.

-I -- I just don't want to ruin my chances of getting funding

for the research I want to do.

Can -- can we probably turn the cameras off

till we get to the end?

-Okay, that sounds good to me.

Fast forwarding. Fast forwarding.

-Suddenly it was through No more resistance.

The change was almost imperceptible,

like the tide coming in.

It was a feeling of elation and relaxation.

Later in the evening, I noticed a silence in my head.

Having cleaned up and had a bath,

we went out and had a steak for supper

to make up for the lost blood

and then went to a party we'd been asked to.

All this took place in 1970.

Now, eight years later,

I can say that the experience of it is as good,

if not better, than I'd hoped.

I think the consequences of the operation,

the regaining the lost energy and buoyancy of childhood

are advantages which should be made available to everyone.

Trepanation is the only way

of permanently expanding consciousness.

I would correct that. Look at that.

Unbelievable.

"Hearbeat," "Hearbeat."

-It's sad when you have compounds you've made to use,

and it's, well, you're gonna retire.

What am I going to do with them?

I had to destroy all my Schedule 1 stuff.

-That's horrible.

You had to destroy compounds that you'd synthesized?

-If they were controlled substances, yeah.

-How did you destroy them?

-Well, mostly you just run it down the sink,

and you have to have witnesses that say,

"I witnessed him destroying it."

-That's ridiculous. It's like an artist

having to destroy all the work that they've made.

-Well, we've got the archives at Purdue.

-You mentioned your contribution to these historically important

clinical experiments with psychedelics,

and then you've also made LSD

for Bryan Roth's work as well, right?

-That's true, yes.

Bryan has had a longstanding interest

in the serotonin 2A receptor,

and he wanted to crystallize one of serotonin receptors with LSD.

And he said, "Could you make some?"

I said, "I can make some for you."

-And now he's trying to take that to a new frontier with

I think he calls it Ultra LSD.

Is that the name of his project?

-I don't know.

You'll have to ask him about that.

I don't know about Ultra LSD.

-My mom had schizophrenia and had her first break

when I was probably 5 or 6.

Obviously, that had a big effect on me.

One of the main goals of our research

has been to find better drugs for treating schizophrenia.

The serotonin receptor I study, 5-HT2A,

you know, it's known to be a target for psychedelics,

there's no question.

And also some of the most effective drugs

in treating schizophrenia block the activity.

That in itself has been, you know,

really intriguing to me.

How can, you know, one receptor, you activate it and, you know,

people have this literally mind-blowing experience?

When you block it,

Some people with schizophrenia get a lot better,

and why that is, we don't know.

I haven't cured schizophrenia.

I saw this. This is a big.

I told Dave, "Our work is done, Dave."

So basically the idea is we have this virtual library

of small drug-like molecules,

which now, my collaborator tells me,

is 34 billion compounds.

So it's this huge universe of chemical scaffolds.

And through the computer, basically,

you can take each of those compounds in

and see if -- if it fits in the receptor.

So for the 5-HT2A receptor, for instance, our goal

is to come up with 100,000 novel scaffolds.

-It would be amazing.

-We can do it. We're doing it.

-With the characterization of the 5-HT2A receptor,

Roth has begun the in silico screening of millions

of virtual drugs on a virtual receptor,

1,500 parallel processors that may exceed the output

of all the medicinal chemists

and pharmacologists in the world.

Should Roth succeed,

the product will be countless novel psychedelic scaffolds

that may be more potent than the lysergamides.

He dubs this process...

...or ultra LSD.

-We have the -- some now that are nothing like

anything you've ever seen before.

I can say that. -It's very exciting.

-I can't say anything else about that.

Yeah, yeah.

-With the careful use of a psychedelic,

you can change your internal setting

so that you're right up there.

I'm very excited about the future.

I think we're at an amazing point

'cause now we move to the next stage in the game.

Science has replaced religion

as the code of behavior, or code of belief.

It's quite the false god in many ways.

At the same time, it's quite a useful tool to explore.

How do these things change our very basic consciousness?

Birdie was my simple consciousness,

and I'm very excited for the future.