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.