All language subtitles for The Psychedelic Drug Trial

This programme contains
some strong language

I was the roots of a tree
and I was underground

and I was connecting with
everything out there.

Wow. Goodness me.

I flew into my body
and I was just looking around

this beautiful cathedral.

Everything just looked, like, alive,

which is the opposite to how I felt
about everything.

In 2019,
a pioneering drugs trial began.

I felt trapped and then I flew
high up into the sky,

and it was just this kind
of beautiful moment

of feeling...feeling free.

HE LAUGHS

A radical new treatment
for depression.

So when you're ready,
climb on board.

Depression is the leading
cause of disability in adults

in the Western world, more than
cancer, more than heart disease.

A significant number of sufferers

report no benefit
from antidepressants.

Now a team of British researchers
are convinced psychedelics

could be the answer.

Why did it take so long
to do this research?

Because these drugs are illegal.

For the first time,
a leading antidepressant

will be pitted head-to-head

against one of the oldest drugs
known to man...

Here are the capsules.

..magic mushrooms.

There is huge potential

and there is also huge risk,
but it is very exciting

that something that grows
in the ground can do this.

Synthesised from a Mexican mushroom
over 60 years ago,

psilocybin is a Class A
hallucinogenic drug.

Supplying it can get you
a life sentence.

Only very few people are allowed
access to the pharmacy,

so it's very secure.

Will just two single doses
of psilocybin

alongside intense psychotherapy

give new hope to people suffering
from depression?

I didn't know what was
going to unfold.

Wow. Crikey.

I just embraced it.

HE LAUGHS

I'd been subatomically picked apart.

THEY LAUGH

I was just looking around
like, "Wow!"

That was extraordinary.

Why am I doing this?

Why do I want to make myself
a guinea pig?

When you're ready...

If psychedelics can
change the world,

let's put it to the test.

See you on the other side.

I have something very special here
you might not have tasted before.

They're mulberries.

All right, aren't they?

Yeah, they're good, actually.
Oh, that's so yummy.

I've given a lot of drugs
to human beings.

I've probably given more different
kinds of drugs to human beings

probably than anyone alive,
or ever, maybe.

In fact, almost every class of drug
that we know of

that affects the brain I have
studied over the last 40 years...

There. Go on, son! There it is!

Quick! Go! Good boy!

..and that gives you insights into
how you might then develop a therapy

to deal with a disorder
like depression.

Not that ball, this ball.

In January 2008, Professor
David Nutt was appointed

to oversee the Government's Advisory
Council on the Misuse of Drugs.

NEWS: ..Professor Nutt,

who's an expert in the effect
of drugs on brains...

A year later, he was sacked.

He has been sacked after insisting

that alcohol and cigarettes
are more dangerous

than cannabis and ecstasy.

The Home Secretary, Alan Johnson,
said he no longer had confidence

in the advice being given
by Professor David Nutt.

I had to go anyway because I just
couldn't bear to mislead the public.

They wanted me to support
their policies

and their policies were so wrong.

So, no, I couldn't do it.

Since then, David has continued
to campaign

for an evidence-based approach
to drugs policy,

and the current trial is his most
ambitious to date.

So the trial is a comparison of two
potential treatments of depression.

One is an established treatment.

It's called escitalopram.

That's the latest and probably
the most powerful of what we call

the SSRIs - selective serotonin
reuptake inhibitors.

And they are the sort of mainstay

of modern first-line
treatment of depression.

What we're doing is, we're looking
to see how psilocybin as a treatment

for depression compares
with this gold standard.

So, the lead scientist is Robin.

Come up through the ranks,
PhD student,

and now he's running the
psychedelic centre in Imperial.

What defines us is our focus
on psychedelic phenomena,

and the depression trial
is the most ambitious trial

that we've ever attempted.

It's very much our flagship study.

Then we have a lead therapist,
who's Ros Watts.

Ros is now training
other psychologists.

She's a clinical psychologist.

I don't even think there is a title,
actually, for what I do yet.

So I guess I am a kind of prototype
psychedelic therapist,

but it's quite new, so...

Yes, there aren't many
of us around.

If we can pull it off, then it
really does bring psilocybin

into the treatment arena
as something to be considered.

If the trial turns out to be
positive, that could open up a door

to a revolution in the treatment
of depression.

HE EXHALES

DIRECTOR: Cool. So nice and relaxed.
No pressure. Cool.

It's a small sample size
for a clinical trial -

59 carefully screened people
with long-term depression

have been recruited
for this radical new

double-blind drugs trial.

I've had depression right
from the start.

It came and went like the weather,

and I seem to have no control
over it and no understanding of it.

It's an all-consuming blackness that
just sits on top of you

and you can't talk
yourself out of it.

Over a six-week period,
the participants will be split

into two groups. No-one will know
who is on which treatment,

not even the clinicians.

The first group will receive
two high doses of psilocybin

three weeks apart, and take home
a course of pills

that look like antidepressants
but are just placebos.

The escitalopram group receives
two placebo doses of psilocybin

and a six-week course of
the antidepressant.

Strict medical and therapeutic
protocols are in place to ensure

the safety of all the participants.

Go on!

Hey. Good girl.

Steve has lived with
depression for 25 years.

I was first diagnosed shortly
after I divorced.

And it hit me pretty hard,

and I had to try and come to terms
with it in my own way.

In 2000, he made the difficult
decision to leave South Africa

when his ex-wife relocated
to the UK

with their two young daughters.

I didn't have a choice, really.

I had to draw a line under what I
was doing and come over myself.

I'd run out of money. Literally,
I had no more rent money.

Things were so bad at times

that I found it hard to put
a foot out of bed

in the morning.
That's where I found myself.

Do dogs like bean pods?

These dogs, not so much.

Now, 16 years into his
second marriage, to Jane,

he's still battling with depression.

One feature of Steve that I've
always found quite challenging is,

he very rarely smiles...

If you've got a fresh one,

you can twist it.

That looks a bit dodgy.

..and when Steve gets
really stressed,

he gets angry with people,
including me...

Do you want to get some bread?
Mm-hm.

..and is very difficult
to live with as well,

because it's as if nothing matters.

It's hot.

And when he's in that state...

You can. I'm hungry.

..it's very difficult for him
to step away from it.

A traumatic experience can lead
to negative ruminative thoughts

that go round and round,
becoming all-consuming.

People are internally focused
on themselves and they're chewing

over certain repetitive
thoughts, like,

"I'm worthless, there's no hope,
it's all pointless."

What time are you going off?

Early.

Like, I've got to be...
I've got to be...

Because I'm insular,
I tend to close up.

Perhaps I'm at fault here,
but I don't share a lot of it

with her or anyone else.

Steve was on antidepressants
for over a decade.

Now he's looking for
an alternative.

I had to find a way out.

I've got to find a different
way of living with

this feeling of joylessness.

THEME MUSIC AND APPLAUSE

Hello and good morning.

Are you feeling depressed? Suicidal?

Well, this pill could solve
all of your problems.

It's called Prozac, and it may mean
the end of depression as we know it.

Launched in 1988,

the first successful SSRI
was Prozac.

By 2005, 54 million people had
taken it worldwide.

I can cope with the kids.

I can cope with family life.

I hold down quite a good job.

Now over seven million people take
antidepressants in England

every day, but they can have
unpleasant side-effects,

and a significant number
of sufferers don't respond

to the medication.

I've been on and off antidepressants
for years.

They've usually had quite a few
side-effects.

I felt kind of quite numb

and I wasn't able to really
fully explore my emotions.

And in the end, I decided to come
off them because it wasn't helping.

As a clinical psychologist, I guess
I saw more people

who found SSRIs helpful.

I'm very, very glad they exist,
but I think we've probably maybe

just overprescribed them.

Ali, a paediatric nurse,
has been on antidepressants

for 12 years.

The side-effects are awful.

I put on, like, five stone
in the year and a half.

I had awful nightmares,
sleep paralysis, horrible itching.

It always brought more problems.

Psychedelic drugs were not something
she had ever considered.

I knew a couple of people had taken
magic mushrooms

and they said it was a bit odd.

So, yeah, it was not something
I've ever been near

or was intending to go near, ever.

Five years ago, Ali's depression
took a turn for the worse,

and then her best friend Laura
took her own life.

We had a lot of laughs,
a lot of fun.

But we also really understood
each other.

The last five, six years
have been just

concentrating on staying alive,
really, I guess.

She's been off work for ten months.

I didn't think I could
concentrate enough.

And I obviously wouldn't want to
put patients' safety at risk.

The drug trial represents
a lifeline for Ali.

I thought I would try it
and give it a go.

I'd kind of come to the sort
of realisation that

if it didn't work then I probably
would end my life.

All the participants have to stop
their current medication six weeks

before beginning on the trial.

This is only ever done under expert
medical supervision.

The first day is preparation only.
No drugs.

If you have any uncomfortable
sensations in your body,

don't try to distract or avoid.

They are taken on
a guided visualisation

to mentally prepare
them for a psilocybin trip.

Instead, try to really feel them.

They're messages from your body
that want to be heard...

It uses the analogy of a
psilocybin experience

being like a deep-sea dive.

..and you have a torch. Shine your
light on the murkier places.

So the idea of diving down into
those deep waters

and how dark and murky it can be...

Explore everywhere.

..because people just don't have
any frame of reference.

They have no idea what to expect.

I tried to pretend
I was really cool about it...

THEY LAUGH

..but I always felt
pretty terrified, actually.

I thought, "I can't do this.
I really can't do this."

If, tomorrow, you don't want to do
it, that is totally fine.

The next day is dosing day.

Neither the participants
nor the therapists

know if they're getting
a placebo or the full dose

of the Class A hallucinogenic drug.

Trial manager Bruna Giribaldi
is responsible for delivering

the drugs to the clinicians.

Because we're working with
an illegal drug,

this place is very secure.

Only very few people
are allowed access

to the pharmacy where it's stored.

We also need authorisation
from the Home Office.

It took Bruna two years to get
authorisation for this drug trial.

Everyone in the study is blinded.

In order to maintain this blind,
every capsule and then every bottle

containing the capsules
looks identical,

regardless of what's inside them.

It's quite a special process for me.

When I hold the bottles,

I just think in my head how much
suffering they're going through

right now and how much
potential this has to help them.

Ros brought the capsules
in in a little bowl,

and I just held the bowl for ages,

staring at them, thinking, "I don't
know if I want to do this."

Ros and a team of therapists and
psychiatrists conducting the trial

ensure all the participants are
carefully supervised at all times.

These drugs are not free
of unwanted effects.

The one that's most concerning is
that you might trigger

a psychotic reaction in
someone predisposed.

So we exclude anyone who's ever
been psychotic,

or anyone who has a close family
relative who's got psychosis.

Amazing.

After I took them, we just talked
for a while and looked through

some books, and talked rubbish
for a little while, I think.

And then I started to feel
a bit odd.

Typically, it takes around
half an hour for the psilocybin

to start having an effect.

I was getting a lot of weird,
like, tingling sensations.

And that was when I realised,
"Oh, crap.

"I think this might be a
bit strong!"

Go with the music. Go with
wherever it takes you.

So I kind of had to steel myself
a little bit and remember everything

that Ros had told me -
like, you have to really commit

and dive into it.

I was still aware of my body
at that point, so I knew,

logically, I was safe, so I just had
to kind of go for it.

And then as soon as I did, that was
when it all just went a bit mad.

I flew into my body.

I was just looking around
this beautiful cathedral.

I was just looking
around like, "Wow!"

It was just this really beautiful
feeling, like, "Oh, I'm fine."

I think that was when I felt
welcomed by it

rather than scared of it.

Once it's absorbed by the body,
the psychedelics' effect is fast.

Psychedelics work on the 2A
receptor, which is in the cortex.

When you stimulate that receptor,
the brain goes into the psychedelic

state instantly, and that state,
we believe, allows people

to overcome their depression
by reframing their relationship

with the current stress
and past stressors.

The 2A receptors promote plasticity
and learning in the brain,

and when stimulated by psilocybin
are believed to disrupt

the negative ruminative thought
patterns associated with depression.

The psychedelics turn that button
on very strongly, and that turns

on plasticity very strongly.

To increase plasticity is to say,
in a sense, I CAN be changed.

Yeah, I could really breathe
and really feel space around me

whereas I'd felt really crushed,
I think, for a long time.

PULSING

And my heartbeat was really loud
in my ears, and then it just got

quieter and quieter really slowly.

And my breathing just... I kind
of didn't feel like I was breathing,

but I didn't feel like I needed
to breathe,

I just felt really peaceful.

I felt like myself

and I was kind of...

I was really happy to be myself

and be there.

Just a really incredible feeling.

Where you're working towards is
like a parting of the clouds

in some way.

Everything just looked alive,
I guess,

and colourful and interesting,

which is kind of the opposite of how
I felt about everything.

Everything felt pointless when
I was depressed

so it was a real switch,
like, instant switch.

The next day, participants come
in for an integration session

where they work
through their experience

with a highly trained therapist.

These sessions play a fundamental
role in the treatment.

The more you thought everything's
going to be OK,

the more it actually did
get OK? Yes...

The psilocybin session is opening
a door to something

and the integration session is
everything that comes after that

to help somebody create some meaning

from what they saw
when that door was opened

and bring it back to their lives.

The way it changed how I felt was
a lot stronger than I'd anticipated.

It's different to anything I can
imagine being able to experience.

Yeah, just, yeah... Mad.

I would consider most medical
treatments for depression

as managing the symptoms
of depression as best they can.

And then I would see psilocybin
therapy as more about

opening people up so they
can receive

much, much more from the world.

When I caught the bus
on the way home,

I had, like, a protective bubble
around me.

I was stood at the bus
stop thinking,

"I don't feel really
anxious. This is really weird,"

cos usually I would be worrying

about how I'm standing or just
really overanalysing everything.

And I just thought
"I just feel really relaxed.

"This is so weird."

A lot of people watching
this programme might say,

"Why have we only just started
studying these drugs as therapies?"

That's a very pertinent question,
because in the 1950s and '60s,

psilocybin was a medicine,
as was LSD, interestingly enough.

Among these drugs,
the hallucinogens,

are included mescaline,

a chemical taken from
the peyote cactus,

psilocybin, extracted from a
variety of Mexican mushroom,

DMT, synthesised from
the compound tryptamine...

..and of course, LSD 25...

The National Institute of Health
in America

funded 130 or more
trials of psychedelics.

40,000 patients,

1,000 publications. And overall,

the results were very positive.

We gave them a larger
dose individually,

and have each one of them cared
for by one of these teams.

If you use them right,

if you use them in a situation

with trained therapists guiding
people through their experiences,

the outcomes are very,
very positive.

We bring these men back

every four months for three days,

and this follow-up
is quite important.

Psychedelic drugs were not just used
for medical research in the 1960s...

Turn on...

..tune in...drop out.

..they were also enjoyed
for pleasure.

But for some, it can be terrifying.

It's like everything
is falling apart.

No matter which way I was facing,
it was just real frightening.

By the late '60s, in some sections
of society,

moral outrage against recreational
drug use had reached fever pitch.

America's public enemy number one
in the United States is drug abuse.

In 1971, President Nixon made
81 substances, including psilocybin,

illegal in the US.

The United Nations Convention
on Psychotropic Drugs soon followed,

and by the 1980s, the war
on drugs was at full throttle.

We're after you.

The pursuit will be relentless.

Relentless.

The effort will get greater
and greater

until we've beaten you.

Medical research became
prohibitively expensive.

Psychedelics were collateral
in the war on drugs,

and the criminalization and
the banning of psychedelics

is the worst censorship
of research -

not just medical research,
of research -

in the history of the world.

It took half a century for
medical research into psychedelics

to restart in earnest, with
Robin Carhart-Harris and David Nutt

leading the charge in the UK.

In 2012, Robin and David completed

a ground-breaking brain
imaging study

into the effects of psilocybin.

They revealed that psilocybin also
disrupts parts of the brain

known as the default mode network.

The reason we started researching
psilocybin in people with depression

was because we had done
the brain imaging studies,

because we had shown
that psilocybin disrupts

the parts of the brain that
cause depression.

This default mode network does
the most abstract of functioning.

So, things like our ability

to have a sense of self,
a personal narrative -

"This is me, I can imagine
the future" -

but it's most active
when we daydream.

They could have called
it the daydream network, in a way.

In depressed people,
daydreaming can be

very negatively focused
and damaging.

People come in with a very strong
default mode network,

which is very rigid,
it's very entrenched.

What psychedelics do,
by deactivating the sense of self,

they enable people
to connect to everything else.

It might feel quite challenging
out here, navigating...

I'll take it really slowly...
There's no rush.

Steve is just beginning
his first dosing session.

I have a feeling I should be saying
something profound.

Oh, no. See how it goes.

There's no question
I was nervous.

You're taking a step
into the unknown.

It probably took 20,
30 minutes to feel the effects.

And it was as colourful
as anything you could imagine.

Just colours that perhaps I'd never
seen before,

and I was seeing them all together
at the same time.

I was inside a kaleidoscope.

And these colours were just
playing out

in the most extraordinary patterns.

Beautiful and...

..wild. Wild beyond imagining.

I felt that I'd been subatomically
picked apart.

The dandelion clock just shhh...
Blowing away in the breeze.

That's how I felt.

And I was left with nothing.

My goodness.

I was the roots of a tree

and I was underground

and I was connecting with everything
out there.

And the thing that
I really felt most...

HE LAUGHS

..was a joy.

Joy like I'd never experienced.
It is...

It is really, really,
really powerful stuff.

GENTLE LAUGHTER

There was a point in the process
where I was confronted with

my own mortality really strongly.

It was a felt thing.
It was, "You are going to die."

And I had a very real sense
of being shown that...

..because I needed to be reminded
to get on with my life

and make the most of it.

Mat is a photographer and
film-maker who lives in London.

You can be carrying this heavy
burden with you...

..and people who don't know that you
have that struggle

might not even know that
that's going on.

It's something that I've had
for the most part of my life.

On the prep day...

If you'd like to have a seat
there, on that blue chair.

I'll get you some water.

..I had no expectations, really,
of what it would involve.

I just kind of went into it
with open arms, really.

So why don't you tell me
a little bit about...?

So the prep day involved just
chatting about how I was feeling,

a bit about my depression history.

I struggled a little bit in school
through kind of bullying...

Mm.

..and I think that affected
my self-esteem. Yeah.

Bullying at school was a really
difficult time in my life.

I wasn't well-liked, and I became
very anxious and insecure,

and life kind of went on
with these feelings, really.

Is there someone with you
at the beginning?

The whole way through. The whole way
through this whole thing?

Yeah. OK. Cool. Yeah, yeah, yeah.

And you'd never be alone.
Yeah. Always with two therapists,

the whole way through.

Reassured, Mat comes in
for his dosing day,

ready to embrace the experience.

Do you want to get comfy? I was just
thinking, do I need to...?

Are they here?
Have the drugs arrived yet?

They've arrived, yes.
They have arrived.

OK, so we're ready to go,
aren't we?

VOICEOVER: I felt very relaxed.
I felt very safe.

This bed's so comfy!

VOICEOVER: I just didn't hesitate.

I just took the pills.

And as the music started
to evolve,

I just started to go on
this amazing journey.

Initially, there was just a sense
of just a kind of weight lifted.

I almost felt like I was
in a computer game.

There were lots of patterns,
and I felt like I was...

I was travelling between
different realms.

There was a moment where I felt like
I was in deep, deep water...

..and I was looking down
into the abyss.

And suddenly I had this sensation...

..I was an observer to my body
being released to the deep.

I just started bawling my eyes out.

I haven't really cried properly
for a long time.

But I didn't feel scared
or frightened. It felt OK.

I was lying there, and I just...

the tears were pouring out of my
eyes, but they weren't sad tears.

They were... They were joyful tears.

Oh...fucking hell!

Phew!

VOICEOVER: I felt really happy,
and I just...

I remember thinking I could die
in this moment, and it would be OK.

People have psilocybin and they
feel these things and trauma that's

been repressed and held on to gets
released, and the transformational

moments where it is,
where someone can suddenly release

some pent-up tears that they
haven't cried for 20 years,

or someone can suddenly
experience joy or beauty,

or something that they haven't felt
for ages,

or suddenly feel a sense of
forgiveness for something

or love for something or hear a
piece of music and it touches them.

Whoever came up with this soundtrack
is a fucking genius.

VOICEOVER: There was a clear sense
that depression and anxiety

doesn't exist where I am now.

We're here whenever you need us.
You've done so well.

Really brilliantly.

I just felt beautifully at peace.

You know, during depression,

you ruminate and think about
a lot of things.

Psilocybin taught me that
I'm so much more than thought.

I am...
I am separate to thought.

Although some participants
don't have such strong experiences,

Mat wasn't alone
in finding psilocybin revelatory.

There has been a fundamental shift
in myself,

which has allowed more light
to come in.

You sort of lose your analytical,
critical mind, or at least I did.

I definitely had probably 30 years
of therapy in that afternoon.

I must have cried
for six hours solid.

Psilocybin opened my heart,

which had been closed down
and locked down for so many years.

Thank you, psilocybin.

Nadine is an artist who lives
with her husband in East Sussex.

In the last couple of years,

I've been focusing
on autobiographical drawings.

It's almost like these characters
have started emerging.

It feels kind of almost like
an eternal struggle

or heaven and hell or something.

I hadn't realised until recently

how much it has reflected
my depression and my anxieties.

It's kind of almost like
internally, I feel that inner sense

of turmoil and flux.

She was diagnosed with depression
in her early 20s.

It's a deep sense of sorrow and loss

and sense that you're never
going to amount to anything,

and then you start spiralling over
the same territory.

You're sort of chewing
over and over it.

It's exhausting.

VOICEOVER: You don't know what to
do, and you feel a bit powerless -

that's difficult.

How do you actually impact that?

How do you help?

The plane's back.

After years on and off
anti-depressants,

Nadine would like to try
something different.

Maybe it's possible
with this psilocybin

that actually,
instead of numbing you,

t maybe lights you up a little bit,
you know,

and I would really want
to experience that.

You know, I'm just curious.

But taking that first step
at Imperial College is a challenge.

For me, being able to make decisions
can be quite difficult.

VOICEOVER: I'm thinking, like,
why am I doing this?

What would happen if I lost control,
or if really dark things happened?

Why do I want to make myself
a guinea pig?

Their depression is
very, very severe,

but somehow they're able to
trust us enough

to do this quite unusual thing
that could hurt as well as heal.

That's when it can be
more challenging.

That's when the experience
can feel really uncomfortable.

VOICEOVER: We want to make
sure people understand how intense

it can be and how they might go
through the most painful experiences

of their life. They might be
experiencing them again.

It's unpredictable.

Obviously, I was quite anxious.

But, yeah, I kind of took it
sort of one by one.

And then there's a certain point
where you're told to get yourself

comfortable and you have
the mask on, and earphones,

and you're listening to music.

You become extra sensitive
to yourself,

"Am I feeling anything,
or is that just a suggestion?"

Who knows?

But for Nadine,
there are no noticeable effects.

After about 20 or 30 minutes,

I realised that really, if anything,
it was very, very minimal.

I couldn't really tell.

If there's too much anxiety
or stress or anything,

it's very easy for it to tip over
quite quickly into a position

where I feel I need to kind of
shut down or remove myself.

And at that point, I was encouraged

to kind of stay with it
for quite a while.

Nadine is in the Escitalopram group.

I was very, very upset.

I felt extremely disappointed,
angry at the trial, you know,

like I'm not
in a great place.

And this makes me feel even worse.

She heads home with a course
of antidepressants.

SSRIs work to increase serotonin
in a part of the brain called

the limbic system.

That's the emotional circuit.

And that system is overactive
in depression.

By dampening down that system,
you become incubated against stress.

You become more resilient
to the turmoils of life.

General practitioners usually very
quickly turn to antidepressants.

So I was put on antidepressants
to help stabilise the situation,

which they did do at the time.

I mean, there are times
when I felt so low,

taking antidepressants
felt like a life-saver.

Escitalopram is one of the leading
SSRIs available.

In numerous medical trials, it has
been shown to lift the depression

of around half of sufferers.

It takes up to six weeks
to start working.

But Robin and David believe
that psilocybin works better

and it works faster.

So when we set out to do this study,
we realised that we were comparing

two very different kinds
of treatment.

Escitalopram, you know, you give
on a regular basis day after day

after day for six weeks.

Psilocybin, you give a shot day one,

and the next second shot
three weeks later.

So we're trying to collect data that
reflect both of those approaches.

So we're using standardised scores.

There are standardised scores
for depression.

We're also using
patient-related outcomes,

because these are becoming
more and more important.

It's all very well for the doctor
to say you're better,

but, if you don't feel better,
you're not better.

And now I get to the data analysis,
which is really exciting

because we get all the results
and see how everyone's been doing

and what the science tells us.

Hey, Bruna, how are you doing?

I'm good, how are you?
Yeah, I'm good, thanks.

It's two-thirds of the way
through the trial,

and Robin is keen to see the data
Bruna has collected so far.

We have lots and lots of data.

They start by looking
at suicidality -

how suicidal the two groups felt.

This is escitalopram. OK.

The score went from 168 to 173,

so a minor increase.

Yeah.

So that shouldn't happen
with a treatment that

is meant to be a top
antidepressant drug. Yeah.

Why isn't suicidality dropping?

So what happens with psilocybin?

With psilocybin,
it goes from 157 to 96,

so it does drop by a lot.

Which is amazing.
You can say that again.

Yeah. Wow.

But the bar any new medicine
has to cross is extremely high.

They have to prove that
the difference in performance

between psilocybin and escitalopram
is statistically significant.

It's not significant.

So... Are you kidding me?

Yes, it is.

Despite a notable difference,
with the current data,

the difference isn't yet
great enough.

It doesn't actually count
as significant.

Oh, are you sure that's right?

That just...

..doesn't seem right to me.

What I did was...

In a drugs trial...

..this data here...

..the key is to eliminate doubt
as much as possible.

All of these statistical tests
are about how do you deal

with uncertainty, really.

And so what you...what you're doing
is you're testing your confidence

in the result.

That is not a result that you could
have got through just random events.

The data is promising,

but for the trial to stand up
to scientific scrutiny,

it has to be bulletproof.

OK, so the criticism's
going to come back.

I'm going to be... You know,
if I was to criticise this,

I'd say you've undervalued
escitalopram,

because we know, in the real world,
it does work as a licensed drug.

You've shown it works, right?

Then people could say, really,
you're telling someone

and their son or daughter who is
suicidal that they have to wait

in order to get an improvement?
Absolutely.

And then their suicidality score
might not even drop, you know.

And they have to deal with
the side effects as well...

You've got to be very careful you
don't say escitalopram doesn't work,

because it clearly does work.
It's got a licence.

Escitalopram is seen
as a gold standard

in the treatment of depression.

Psilocybin will have to
prove its worth.

I'm not defending it.

I'm just saying that we need
to have an answer to that criticism.

I'm looking for weaknesses...
Yeah.

..because everyone else is going to!

Thanks, everybody. See you soon.

To investigate the optimal way

of delivering psilocybin
as a treatment for depression,

the team have included a second dose
three weeks after the first.

Prepping my mind for the
second dosing session was tricky,

because themes had come up
that I needed to maybe focus on.

I almost knew what was coming.

I took the tablets, and it felt like
it took a little bit longer

for things to start to happen.

I remember initially feeling very,
very tense and uncomfortable.

And, as the effects
of the psilocybin grew,

I suddenly had this
really strong vision.

It was this little boy
trapped in a box,

and he was banging on the side,
saying, "Get me out, get me out."

And this morphed into
this white bird in a cage,

and it was flapping its wings,
obviously in distress,

and I had this real sense that
that was me.

I felt trapped.

I was an observer to a scene
that I was also in,

and that kind of felt
kind of quite strange...

..but, then, in a breath,
I realised

that I could just open the cage
and let the bird out.

And that felt so easy. That bird
didn't need to be trapped,

and I didn't need to feel trapped.

I had the power
to just open that door

and just let that bird fly free,
and I became that bird.

I flew high up into the sky and...

..and it was just this kind of
beautiful moment of feeling free.

The essence of why this model
is good is because it sees pain

as something to be learned from,
not something to be ignored.

So, rather than suppress pain, you
open yourself up to engage with it

so that you can process it,
move on from it,

and also learn from it.

Talking therapy helps you
believe something to be true.

Psilocybin helps you
know it to be true.

And I think that's why I felt,
in my case,

psilocybin worked well for me,

because it showed me so much
that I now know to be true.

I just feel so much more optimistic
about things.

I just feel a little bit more
in charge of my own destiny,

and I'm just really going to enjoy
that ride,

because I just have this new insight
into life,

and I just want to
make the most of it.

When she returns
for her second session,

Ali's been off antidepressants
for over two months.

I wouldn't have said I was, like,
depression-free

after the first dose, but I wouldn't
have said I was unhappy.

I was kind of determined
to keep going with it,

but I wasn't sure if I would be able
to actually do it.

Going through
a psilocybin experience,

it's a very courageous thing to do,
so for somebody like Ali,

having gone through that,

it's the beginning of the journey
for her, I think.

The second time, I think
I felt the effects quite quickly.

The beginning was pretty terrifying,
the second one.

I felt like my whole body
was humming

and bits were being
pulled off of me.

I knew that was kind of
me just dying

or falling apart, I don't know.

And then I had this sensation which
was kind of like a claw on my head,

and it was just pushing me down.

I was kind of holding on to Ros
and Ashleigh for dear life, I think.

You can feel like you're dying.

You can feel like
you've lost everything.

You can have some
quite frightening encounters.

And if, deep down,
there is a bedrock of trust,

then no matter how frightening
things become,

there is that sense
of the foundations are there

and you're safe.

I kind of had to make a decision
to go down this one tunnel,

which looked pretty nasty.

There were lots of these kind
of like orbs of colours all around.

And I realised those were kind of
memories and people

and things that had happened.

I've always had this sort of fear
that maybe I'm an awful person,

but I think that was telling me
that, like, "You're OK."

And then I came across
this one colour...

..and it was a really lovely
purple colour.

And that was my best friend, Laura,

who died a couple of years ago.

I spent a lot of time with her,
which was really lovely.

And I kind of cried so much
that I became a river.

Then Laura joined me, and we just
flowed along together for,

it felt like hours.

I just felt really lovely
to be with her,

and I felt a lot of grief.

I just really didn't want to leave,
but I knew I'd have to.

I realised, coming out
of the second one,

that a lot of my depression the last
couple of years was actually grief.

That's why i's really good to cry.

I think I was stuck in that phase
of grief, and through the

second experience, I felt like
I'm able to move through that.

I felt like a new person
afterwards.

It was brilliant.

In that afterglow period,
people are very sensitive,

and they they can be quite raw
emotionally, as well.

On the bus, you probably
can have a little quiet weep,

and nobody will notice.

It's difficult for me to say goodbye
to people,

because they're often
feeling much, much better,

and they're feeling in a great place
and are inspired.

And then, unfortunately, what
happens without further sessions

or further therapy,
people tend to close up again.

And promise me you'll get in touch
if you're feeling really wobbly.

The ruminations, the negative
thinking starts up again gradually,

and then usually after
about six months,

people describe their depression
has come back again.

For most participants,
this isn't a magic cure...

Morning, folks. How you doing?

Make yourselves comfortable.

If you'd like to hang your jacket,
there is a rack...

..but for some, the effects
can last beyond six months.

I'm better.
I never thought I'd say that.

Back at work at his cafe,

Steve is in no doubt what
Psilocybin therapy has done for him.

..just go to the website. Fantastic.
There you go.

I'm not cured.

I don't know if there is a cure
for depression,

but I think I have a better
understanding of my depression.

OK, whoa.

That's a beaut.

Having a better understanding of it
has helped me deal with it better,

and that feels like progress.

I didn't get your name. Gabrielle.

All of a sudden, he was smiling
much more, as if it had taken off

a big heavy lid, like the lid of
a pressure cooker,

that had been pushed down on him.

Oh, yes.

Would you like a treat?

Taken it off and said,
"No, it's OK.

"What's in there, it's OK.
You can let it out."

I mean, it's almost miraculous,
it really is.

It's extraordinary.

So I'll try and
sit as back as I can...

Nadine was in the
Escitalopram group,

and it's been six months
since she finished the trial.

I decided to stay
on the Escitalopram,

because I didn't really have any
particularly horrible side-effects.

What I noticed was that I was
able to make decisions.

I mean, I can't describe what
being able to make decisions means,

you know,
because it gives you agency.

I'm really pleased I did the trial,
because I think, apart from anything

else, there was a strong sense
of validation of your experience,

which comes by being accepted
onto a trial like this...

..and that's been really powerful.

The trial is complete.

Robin is visiting David Nutt
with the full data set

to discuss the results.

Hi, good to see you.

We got these forest plots
with all of the main outcomes.

The depression outcome's at the top.
Right.

It's the moment of truth.

OK, so we chose the self reported
core depressive symptoms

to be the primary outcome
because we believe that the patient

should be the person that tells you
whether they're better off.

The most important result
in this study is the measure

of the participants'
self-reported depression scores.

Better sexual functioning...

These results reveal how effective
each drug is at reducing

the core symptoms of depression.

It was much faster, the response
with Psilocybin therapy.

And that's actually interesting.

Really rapidly, the patients
reported a very powerful

immediate effect,
which is Psilocybin.

It's just that Escitalopram
caught up after six weeks. Yeah.

The results suggest that Psilocybin
is as effective

as the antidepressant
in reducing depression...

Work and social functioning...

..and some of the other findings
are even more promising.

..psychological flourishing,

anxiety decreases more
with Psilocybin.

Remission rates, so no longer
having depression. Right.

That was 60% no longer having
depression. At six weeks?

At six weeks.
60% remitted at six weeks?

Yeah. With Psilocybin, it was 30%.
With Escitalopram... Twice as many?

Yeah. Impressive.

So we've got three or four
depression rating scales

significantly favouring Psilocybin.

Wow. Yeah, very exciting. It is.

With a sample size of 59,
and only six weeks' worth of data,

larger and longer trials
are still needed,

yet this trial clearly demonstrates
the scientific worth

of further research.

What we've got here is the best
proof yet of what I've been saying

for 15 years, which is
it is ridiculous to deny

access of Psilocybin.

It is a different way
of treating depression,

and that's hugely important.

There is still a long way to go

before this treatment is available
in the UK.

Mass testing will need to prove
that Psilocybin,

in combination with psychotherapy,
is both safe and effective

in the long term before government
regulators can approve it

for medical use.

In Bristol, a year after taking part
in the psychedelic drug trial,

Ali's life has changed.

I went back to work three days
after I finished the trials.

I'd been off work
for nearly a year at that point.

Just the last few months, I've
actually started really enjoying

work again and not dreading it,
which is really lovely.

Ali's depression hasn't gone,
but it is more manageable.

Now that I've experienced
being depressed since the trial,

and come out of it myself,
that feels huge.

I know I can deal with it now,
so I'm really lucky.

I just hope that it can become
treatment that's accessible.

I always think about
my best friend Laura.

There's just a lot of people
struggling.

I feel really confident
that Psilocybin, when used

in a scientific container
with therapeutic support

and great care for screening,
and everything else that we did,

that its effectiveness
has been shown to me.

Hopefully in future, things
will move towards creating

a fuller kind of
therapeutic programme

using Psilocybin therapy
as its heart.

Oh, that's a great response.

One of the reasons I'm sitting
here is that I think

it's the way forward.

More change has got to come.

It's inevitable.
That's the way I feel about it.

I think if the government
really wants to do something

to help mental health
and help the NHS,

they can't ignore this
as a potential treatment.

It's changed my life.

I just feel really grateful,

and I'm ready to go another
long, interesting life.