All language subtitles for Hamiltons.Pharmacopeia.S03E06.WEBRip.x264

-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.