It's easy to be captivated by the world out there.
It's a fascinating place.
It's deserving of this attention.
But what if we were to invert our focus and look inside?
What would we find?
I study psychedelic drugs for a living,
and the reason why I do this -
apart from good fortune -
is because I think they're special.
And the reason why I think they're special
is that I believe they have a unique ability
to reveal to us the very depths of our minds.
Dreams and perhaps a select few other states
may hint at what lies beyond the reaches of normal consciousness,
but psychedelics, in my view, are really unrivaled in their ability to do this.
Now, many of you will be familiar with the word "psychedelic,"
but I doubt so many of you are familiar with its origins or what it means.
So, psychedelic was a word that was coined in the 1950s
by the British psychiatrist Humphry Osmond,
with reference to this class of drugs that I study,
and it combines two Greek words, "psyche" and "delos,"
which, when put together,
mean "to make the mind manifest" or "to reveal the soul."
Now, I've been fascinated by psychology for most of my adult life,
but one question that has always bugged me
is why can't it prove the existence of the unconscious mind?
Is it because it doesn't exist?
Or is it because it is especially difficult to see?
Now, I've come to believe quite strongly that it's the latter,
but then the key question is
how could we make it easier to see?
Freud famously told us about dreams,
how they're a window in on the unconscious, a "royal road."
But the problem is dreaming happens while we're asleep,
and then when we wake up,
all we're left with is this flimsy memory of what we actually experienced.
So it's while I was studying for my Masters
that I found myself asking whether a drug exists
that could facilitate access to the unconscious mind.
I did a brief library search, and I came across this book:
"Realms of the Human Unconscious: Observations from LSD Research,"
written by the Czech psychiatrist Stanislav Grof in 1975.
So I swiftly took this book out of the library;
I brought it back to my room;
I opened it and I read:
"Many of the phenomena in these LSD sessions
could be understood in psychological and psychoanalytic terms;
they had a structure not dissimilar to that of dreams.
And Freud once said of dreams
that they are a royal road to a knowledge of the unconscious mind,
but to an even greater degree,
this seems to be true for the LSD experience."
And finally: "The capacity of psychedelic drugs
to exteriorise otherwise invisible phenomena
and make them the subject of scientific investigation
gives these substances
a unique potential as research tools for the exploration of the human mind.
It does not seem inappropriate or an exaggeration
to compare their potential significance for psychiatry" - and for psychology -
"to that of the microscope for medicine or the telescope for astronomy."
So, as you can imagine, after reading these things,
I was filled with a very strong sense of purpose and direction.
I wrote to Professor David Nutt, then at the University of Bristol,
and I told him I wanted to study the brain on LSD
and to see whether it looks like the dreaming brain.
Anyway, David was kind enough to allow me to join his team,
and then four years later, I completed my PhD with him.
Soon after that,
I was lucky enough to begin some quite exciting brain-imaging research
with psychedelic drugs.
First with psilocybin, which is the active ingredient in magic mushrooms,
and more recently with LSD.
Now, it's quite difficult to explain to people
how psychedelic drugs work in the brain,
and it's harder still to do that in 18 minutes.
So instead what I'm going to do
is show you a few pictures and give you a few analogies to think about.
So what we're looking at here are communication pathways in the brain.
Each line is a communication pathway
between two different regions in the brain.
And believe it or not,
there's actually an equal number of lines, or pathways, in these two circles,
yet they look very different, don't they?
Essentially, what we're seeing is the normal brain on the left,
where communication is confined
to particular communities, or cliques, in the brain.
So, for example,
visual regions are talking mostly with other visual regions;
this is what happens ordinarily.
Then we look at the psychedelic brain on the right;
there's much less of this cliquing,
and much more of an open, freer conversation
going on across the brain.
Another useful way to think of how psychedelics work in the brain
is to think of what it's like to be an infant:
Experiencing everything is novel;
feeling emotionally labile -
one minute you're laughing and the next you're crying;
having a wildly overactive imagination;
being mesmerized by the likes of Iggle Piggle or Makka Pakka.
It's no coincidence, therefore,
that if you look at how the brain develops as we develop from infancy into adulthood
and you compare that with how the brain changes under a psychedelic,
what you see are kind of mirror opposites.
So instead of a brain becoming more sophisticated as we develop,
more finessed,
but also more constrained,
you have a brain that is simpler and freer in its functioning.
The third useful way to think of how psychedelics work in the brain
is to think of the dream state.
Here we're looking at the effects of LSD on the brain,
and what we're seeing is that much more of the brain
contributes to the visual experience under LSD than it does ordinarily.
And this effect correlated very strongly
with the dreamlike visions that people reported under LSD
when their eyes were closed.
So we could think of both these states, the dream state and the psychedelic state,
as conditions where the brain becomes untethered, or unanchored,
from incoming sensory information.
And then in this state,
it can operate in a more anarchic, freewheeling kind of way,
conjuring up imagery from the very depths of the mind and the brain
rather than relying on sensory information coming into the brain.
Perhaps the most important thing
to have come out of our research with psychedelics
isn't the knowledge of how they work in the brain
but rather some idea of how they may be useful
or how they can be applied.
So, we've recently completed
the first phase of the first step of clinical trial,
looking at psilocybin, magic mushrooms, as a treatment for major depression.
Now, it's important that I make you aware
of the magnitude of the problem of depression;
it really isn't something that should be swept under the carpet
although, unfortunately, often it is.
It's a leading cause of disability, worldwide.
It actually affects some 350 million people.
To put that in perspective,
that's more than the total population of the United States.
And if you care about money, it's also especially costly.
It's the most costly brain disorder in Europe,
and it's annual cost to the U.S. alone is 200 billion dollars.
That's roughly the GDP of the Republic of Ireland.
And depression is quite an insidious disorder;
it's often evident by the absence of something.
That might be the absence of pleasure, or positive mood more generally,
or it could be the absence of the individual themselves;
they may simply not get out of bed in the morning and make it into work.
The depression is the leading cause of absenteeism in the workplace.
But depression can also be more stark in its presentation
and often, tragically, when it's too late.
Some 15% of patients with major depression will take their own lives,
and it's a frightening statistic now that suicide is the leading cause
of death among males under the age of 45 in the UK.
So what can be done about these things?
How effective are current treatments?
Well, the good news is that they're not ineffective.
This chart here shows the relative effect size
of different treatments for depression.
Just to give you some perspective on it,
it's convention to consider that an effect size of 0.8 -
which is where the line is - as large.
So you can see
that antidepressant medications, psychotherapy and placebo
all have pretty large effect sizes in depression.
But even so, around about 50% of patients
won't respond to the antidepressants that their doctors prescribe them,
and as many of 20% fail to respond to any treatment at all.
And it's these particularly refractory treatment-resistant cases
that we're seeing in our current trial.
But before I tell you about our results,
I think it's important that I emphasize to you,
especially to those of you who are naive to the effects of psychedelics,
that an experience with one of these drugs
can be among the most profound of the whole of your life.
So evidence suggests that in terms of meaningfulness,
it can be up there with pretty much anything:
facing death,
falling in love
or bringing in new life.
So the key point is that these are not party drugs;
they're incredibly powerful substances that should be treated with respect,
as they have been by certain cultures for hundreds, if not thousands, of years.
It's also important to emphasize that when we give psilocybin to our patients,
we do so with full legal and ethical approval,
and we simply don't tell them
to chuck a bunch of magic mushrooms down their necks and hope for the best.
We carefully prepare them for their experiences.
They're looked after by a trained team of therapists.
They have two sessions with the psilocybin;
they're looked after throughout,
and the therapists help them make sense of things afterwards.
So, here we can see the magnitude of the effect
that we're seeing with psilocybin so far.
Psilocybin is shown in blue,
and you can see the data at two weeks post-treatment
and three months post-treatment.
Now, I should caution that it's early days yet;
we had 12 patients in the trial at this stage,
now, actually, we have more data and the effects look even better.
But even so, there was several hundred patients in these other studies.
Also, all of our patients knew that they were going to receive psilocybin
whereas these other studies had a placebo-control element -
that's actually what we are going to be doing next.
Even so with these caveats,
you can see that the magnitude of the effect that we're seeing so far
is pretty considerable,
even at the three-month post-treatment period
where they haven't received any treatments from us for that duration of time.
Also remember that our patients had treatment-resistant depression;
many of our patients reported
having had their depression for most of their adult lives.
The average duration of the illness in this sample was 18 years,
yet all of them showed some improvement in their depressive symptoms
for at least three weeks after the treatment.
Some two-thirds, 67%, met criteria for remission one week post treatment.
Remission means they are essentially depression free.
And 42% maintained that status of being depression free
for three months after the treatment.
So to finish, I'm just going to read you a short case report
written by one of the patients in our trial.
He's male, age 52,
has a very long history of depression,
quite severe depression stretching back to his 20s.
He's tried a number of different medications,
all of which haven't worked for him,
and also psychotherapy.
So about his baseline state before the treatment, he says the following:
"For decades, I've battled depression.
The awful feeling that you don't matter, you're not making a difference,
that everyone else is having a better life.
The utter pointlessness of it all, getting no real enjoyment from anything."
Then about the experience, he says:
"There simply aren't words to describe it,
but I can say that the usual negative self-narration that I have
had vanished completely.
It was replaced by a sense of beautiful chaos,
a landscape of unimaginable color and beauty.
I began to see that all of my concerns about daily living weren't relevant,
that they were a result of a negative spiral.
I also felt like I was learning without being taught;
that intuition was being fed.
The fleeting feelings from my past came back,
memories too,
both of which had seemed long forgotten."
Then about the outcome;
this was written a couple of weeks after he completed the trial.
He says, "Although it's early days yet, the results are amazing.
I feel more confident and calm than I have in such a long time.
My outlook has changed significantly too.
I'm more aware that it's pointless to get wrapped up in endless negativity.
I also feel as if I've seen a much clearer picture.
Another side to this is that I feel like I've had a second chance,
like a survivor.
I can enjoy things now the way I used to
without the cynicism, without the oppression.
At its most basic, I feel like I used to before the depression."
If you're curious how this patient is doing in the longer term,
we've collected his six-month follow-up data now;
I'm pleased to say that he's still in remission.
You can see his data highlighted here in blue.
Of course, I've cherry-picked a particularly good example here,
and you can see from other patients on this chart
that at the three-month follow-up period,
they're showing some signs of relapse.
So this is an important opportunity to say that this isn't a magic cure;
it's not a golden bullet that's going to help everyone;
there's much more work that needs to be done
to learn how to optimize this treatment and further test its effectiveness.
But hopefully you've got a sense from that case that I reported,
and I can tell you from many other cases I've sat with now
that when this is done properly -
with the right level of preparation,
good drug effects working in synergy,
with good therapy -
to lift the veil on the mind and exorcise what lies beneath,
it can truly work like a dream.
Thank you very much.
(Applause)