Translator: Tanya Cushman
Reviewer: Peter van de Ven 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)
Dr. Carhart-Harris is the best! The work he's doing is groundbreaking. He's going to be a huge figure of the psychedelic revival