WEBVTT 00:00:21.758 --> 00:00:26.746 It's easy to be captivated by the world out there. 00:00:27.054 --> 00:00:29.113 It's a fascinating place. 00:00:29.113 --> 00:00:32.261 It's deserving of this attention. 00:00:32.891 --> 00:00:37.587 But what if we were to invert our focus and look inside? 00:00:37.787 --> 00:00:39.607 What would we find? 00:00:41.057 --> 00:00:43.026 I study psychedelic drugs for a living, 00:00:43.026 --> 00:00:44.536 and the reason why I do this - 00:00:44.536 --> 00:00:45.975 apart from good fortune - 00:00:45.975 --> 00:00:49.077 is because I think they're special. 00:00:49.077 --> 00:00:52.036 And the reason why I think they're special 00:00:52.036 --> 00:00:54.626 is that I believe they have a unique ability 00:00:54.626 --> 00:00:59.516 to reveal to us the very depths of our minds. 00:00:59.516 --> 00:01:02.437 Dreams and perhaps a select few other states 00:01:02.437 --> 00:01:07.327 may hint at what lies beyond the reaches of normal consciousness, 00:01:07.517 --> 00:01:13.506 but psychedelics, in my view, are really unrivaled in their ability to do this. 00:01:15.426 --> 00:01:21.027 Now, many of you will be familiar with the word "psychedelic," 00:01:21.027 --> 00:01:26.660 but I doubt so many of you are familiar with its origins or what it means. 00:01:26.960 --> 00:01:31.367 So, psychedelic was a word that was coined in the 1950s 00:01:31.367 --> 00:01:34.479 by the British psychiatrist Humphry Osmond, 00:01:34.479 --> 00:01:37.795 with reference to this class of drugs that I study, 00:01:37.795 --> 00:01:41.417 and it combines two Greek words, "psyche" and "delos," 00:01:41.417 --> 00:01:43.035 which, when put together, 00:01:43.035 --> 00:01:48.729 mean "to make the mind manifest" or "to reveal the soul." 00:01:50.369 --> 00:01:55.510 Now, I've been fascinated by psychology for most of my adult life, 00:01:55.510 --> 00:01:58.177 but one question that has always bugged me 00:01:58.177 --> 00:02:02.838 is why can't it prove the existence of the unconscious mind? 00:02:03.288 --> 00:02:06.017 Is it because it doesn't exist? 00:02:06.177 --> 00:02:10.207 Or is it because it is especially difficult to see? 00:02:10.727 --> 00:02:13.782 Now, I've come to believe quite strongly that it's the latter, 00:02:13.782 --> 00:02:15.308 but then the key question is 00:02:15.308 --> 00:02:18.117 how could we make it easier to see? 00:02:18.777 --> 00:02:20.968 Freud famously told us about dreams, 00:02:20.968 --> 00:02:24.528 how they're a window in on the unconscious, a "royal road." 00:02:24.528 --> 00:02:27.806 But the problem is dreaming happens while we're asleep, 00:02:27.806 --> 00:02:29.023 and then when we wake up, 00:02:29.023 --> 00:02:34.566 all we're left with is this flimsy memory of what we actually experienced. 00:02:36.196 --> 00:02:39.010 So it's while I was studying for my Masters 00:02:39.010 --> 00:02:42.245 that I found myself asking whether a drug exists 00:02:42.245 --> 00:02:45.876 that could facilitate access to the unconscious mind. 00:02:45.876 --> 00:02:49.407 I did a brief library search, and I came across this book: 00:02:49.827 --> 00:02:55.395 "Realms of the Human Unconscious: Observations from LSD Research," 00:02:55.645 --> 00:03:00.888 written by the Czech psychiatrist Stanislav Grof in 1975. 00:03:00.888 --> 00:03:03.768 So I swiftly took this book out of the library; 00:03:03.768 --> 00:03:05.946 I brought it back to my room; 00:03:05.946 --> 00:03:09.278 I opened it and I read: 00:03:10.158 --> 00:03:12.625 "Many of the phenomena in these LSD sessions 00:03:12.625 --> 00:03:16.946 could be understood in psychological and psychoanalytic terms; 00:03:16.946 --> 00:03:21.579 they had a structure not dissimilar to that of dreams. 00:03:22.259 --> 00:03:23.638 And Freud once said of dreams 00:03:23.638 --> 00:03:26.728 that they are a royal road to a knowledge of the unconscious mind, 00:03:26.728 --> 00:03:28.767 but to an even greater degree, 00:03:28.767 --> 00:03:32.586 this seems to be true for the LSD experience." 00:03:32.586 --> 00:03:34.806 And finally: "The capacity of psychedelic drugs 00:03:34.806 --> 00:03:38.046 to exteriorise otherwise invisible phenomena 00:03:38.046 --> 00:03:41.065 and make them the subject of scientific investigation 00:03:41.065 --> 00:03:42.243 gives these substances 00:03:42.243 --> 00:03:47.533 a unique potential as research tools for the exploration of the human mind. 00:03:47.533 --> 00:03:50.608 It does not seem inappropriate or an exaggeration 00:03:50.608 --> 00:03:55.125 to compare their potential significance for psychiatry" - and for psychology - 00:03:55.125 --> 00:04:00.919 "to that of the microscope for medicine or the telescope for astronomy." 00:04:00.919 --> 00:04:03.306 So, as you can imagine, after reading these things, 00:04:03.306 --> 00:04:07.596 I was filled with a very strong sense of purpose and direction. 00:04:07.596 --> 00:04:10.987 I wrote to Professor David Nutt, then at the University of Bristol, 00:04:10.987 --> 00:04:14.458 and I told him I wanted to study the brain on LSD 00:04:14.458 --> 00:04:17.688 and to see whether it looks like the dreaming brain. 00:04:18.158 --> 00:04:21.538 Anyway, David was kind enough to allow me to join his team, 00:04:21.538 --> 00:04:24.848 and then four years later, I completed my PhD with him. 00:04:24.848 --> 00:04:26.037 Soon after that, 00:04:26.037 --> 00:04:30.318 I was lucky enough to begin some quite exciting brain-imaging research 00:04:30.318 --> 00:04:32.216 with psychedelic drugs. 00:04:32.216 --> 00:04:37.217 First with psilocybin, which is the active ingredient in magic mushrooms, 00:04:37.217 --> 00:04:41.065 and more recently with LSD. 00:04:43.105 --> 00:04:45.776 Now, it's quite difficult to explain to people 00:04:45.776 --> 00:04:48.169 how psychedelic drugs work in the brain, 00:04:48.169 --> 00:04:50.925 and it's harder still to do that in 18 minutes. 00:04:50.925 --> 00:04:52.586 So instead what I'm going to do 00:04:52.586 --> 00:04:57.846 is show you a few pictures and give you a few analogies to think about. 00:04:57.846 --> 00:05:01.747 So what we're looking at here are communication pathways in the brain. 00:05:01.747 --> 00:05:04.536 Each line is a communication pathway 00:05:04.536 --> 00:05:07.037 between two different regions in the brain. 00:05:07.037 --> 00:05:08.097 And believe it or not, 00:05:08.097 --> 00:05:11.915 there's actually an equal number of lines, or pathways, in these two circles, 00:05:11.915 --> 00:05:13.866 yet they look very different, don't they? 00:05:13.866 --> 00:05:17.576 Essentially, what we're seeing is the normal brain on the left, 00:05:17.576 --> 00:05:20.459 where communication is confined 00:05:20.459 --> 00:05:24.060 to particular communities, or cliques, in the brain. 00:05:24.074 --> 00:05:25.187 So, for example, 00:05:25.187 --> 00:05:30.877 visual regions are talking mostly with other visual regions; 00:05:31.077 --> 00:05:33.097 this is what happens ordinarily. 00:05:33.097 --> 00:05:35.594 Then we look at the psychedelic brain on the right; 00:05:35.594 --> 00:05:37.537 there's much less of this cliquing, 00:05:37.537 --> 00:05:40.647 and much more of an open, freer conversation 00:05:40.647 --> 00:05:43.327 going on across the brain. 00:05:44.007 --> 00:05:47.688 Another useful way to think of how psychedelics work in the brain 00:05:47.688 --> 00:05:51.665 is to think of what it's like to be an infant: 00:05:51.985 --> 00:05:55.047 Experiencing everything is novel; 00:05:55.307 --> 00:05:56.754 feeling emotionally labile - 00:05:56.754 --> 00:05:59.348 one minute you're laughing and the next you're crying; 00:05:59.608 --> 00:06:03.088 having a wildly overactive imagination; 00:06:03.088 --> 00:06:07.546 being mesmerized by the likes of Iggle Piggle or Makka Pakka. 00:06:08.316 --> 00:06:10.617 It's no coincidence, therefore, 00:06:10.617 --> 00:06:15.645 that if you look at how the brain develops as we develop from infancy into adulthood 00:06:15.645 --> 00:06:20.055 and you compare that with how the brain changes under a psychedelic, 00:06:20.055 --> 00:06:22.669 what you see are kind of mirror opposites. 00:06:22.669 --> 00:06:26.596 So instead of a brain becoming more sophisticated as we develop, 00:06:26.596 --> 00:06:27.876 more finessed, 00:06:27.876 --> 00:06:30.066 but also more constrained, 00:06:30.336 --> 00:06:35.674 you have a brain that is simpler and freer in its functioning. 00:06:36.764 --> 00:06:40.249 The third useful way to think of how psychedelics work in the brain 00:06:40.249 --> 00:06:42.336 is to think of the dream state. 00:06:42.336 --> 00:06:46.117 Here we're looking at the effects of LSD on the brain, 00:06:46.117 --> 00:06:48.787 and what we're seeing is that much more of the brain 00:06:48.787 --> 00:06:53.715 contributes to the visual experience under LSD than it does ordinarily. 00:06:54.307 --> 00:06:57.208 And this effect correlated very strongly 00:06:57.208 --> 00:07:00.888 with the dreamlike visions that people reported under LSD 00:07:00.888 --> 00:07:03.248 when their eyes were closed. 00:07:03.458 --> 00:07:07.366 So we could think of both these states, the dream state and the psychedelic state, 00:07:07.366 --> 00:07:11.946 as conditions where the brain becomes untethered, or unanchored, 00:07:11.946 --> 00:07:14.717 from incoming sensory information. 00:07:14.717 --> 00:07:15.837 And then in this state, 00:07:15.837 --> 00:07:19.956 it can operate in a more anarchic, freewheeling kind of way, 00:07:19.956 --> 00:07:23.908 conjuring up imagery from the very depths of the mind and the brain 00:07:23.908 --> 00:07:29.028 rather than relying on sensory information coming into the brain. 00:07:30.528 --> 00:07:32.057 Perhaps the most important thing 00:07:32.057 --> 00:07:34.588 to have come out of our research with psychedelics 00:07:34.588 --> 00:07:36.918 isn't the knowledge of how they work in the brain 00:07:36.918 --> 00:07:39.888 but rather some idea of how they may be useful 00:07:39.888 --> 00:07:41.877 or how they can be applied. 00:07:42.217 --> 00:07:44.019 So, we've recently completed 00:07:44.019 --> 00:07:46.918 the first phase of the first step of clinical trial, 00:07:46.918 --> 00:07:52.958 looking at psilocybin, magic mushrooms, as a treatment for major depression. 00:07:54.388 --> 00:07:57.157 Now, it's important that I make you aware 00:07:57.157 --> 00:07:59.909 of the magnitude of the problem of depression; 00:07:59.909 --> 00:08:03.588 it really isn't something that should be swept under the carpet 00:08:03.588 --> 00:08:06.287 although, unfortunately, often it is. 00:08:06.557 --> 00:08:09.851 It's a leading cause of disability, worldwide. 00:08:10.601 --> 00:08:14.209 It actually affects some 350 million people. 00:08:14.209 --> 00:08:15.507 To put that in perspective, 00:08:15.507 --> 00:08:20.176 that's more than the total population of the United States. 00:08:20.566 --> 00:08:23.588 And if you care about money, it's also especially costly. 00:08:23.588 --> 00:08:26.919 It's the most costly brain disorder in Europe, 00:08:26.919 --> 00:08:31.707 and it's annual cost to the U.S. alone is 200 billion dollars. 00:08:31.707 --> 00:08:34.728 That's roughly the GDP of the Republic of Ireland. 00:08:35.418 --> 00:08:38.206 And depression is quite an insidious disorder; 00:08:38.206 --> 00:08:40.908 it's often evident by the absence of something. 00:08:40.908 --> 00:08:45.678 That might be the absence of pleasure, or positive mood more generally, 00:08:45.678 --> 00:08:48.751 or it could be the absence of the individual themselves; 00:08:48.751 --> 00:08:53.909 they may simply not get out of bed in the morning and make it into work. 00:08:53.909 --> 00:08:59.228 The depression is the leading cause of absenteeism in the workplace. 00:09:00.088 --> 00:09:03.501 But depression can also be more stark in its presentation 00:09:03.501 --> 00:09:06.688 and often, tragically, when it's too late. 00:09:06.688 --> 00:09:11.805 Some 15% of patients with major depression will take their own lives, 00:09:11.805 --> 00:09:15.807 and it's a frightening statistic now that suicide is the leading cause 00:09:15.817 --> 00:09:21.028 of death among males under the age of 45 in the UK. 00:09:22.318 --> 00:09:24.198 So what can be done about these things? 00:09:24.198 --> 00:09:26.824 How effective are current treatments? 00:09:26.824 --> 00:09:30.699 Well, the good news is that they're not ineffective. 00:09:30.909 --> 00:09:33.696 This chart here shows the relative effect size 00:09:33.696 --> 00:09:35.996 of different treatments for depression. 00:09:35.996 --> 00:09:37.913 Just to give you some perspective on it, 00:09:37.913 --> 00:09:41.337 it's convention to consider that an effect size of 0.8 - 00:09:41.337 --> 00:09:43.908 which is where the line is - as large. NOTE Paragraph 00:09:43.908 --> 00:09:45.104 So you can see 00:09:45.104 --> 00:09:50.167 that antidepressant medications, psychotherapy and placebo 00:09:50.167 --> 00:09:54.888 all have pretty large effect sizes in depression. 00:09:55.538 --> 00:09:58.267 But even so, around about 50% of patients 00:09:58.267 --> 00:10:01.989 won't respond to the antidepressants that their doctors prescribe them, 00:10:01.989 --> 00:10:06.406 and as many of 20% fail to respond to any treatment at all. 00:10:06.406 --> 00:10:10.045 And it's these particularly refractory treatment-resistant cases 00:10:10.045 --> 00:10:13.527 that we're seeing in our current trial. 00:10:14.187 --> 00:10:16.620 But before I tell you about our results, 00:10:16.620 --> 00:10:19.117 I think it's important that I emphasize to you, 00:10:19.117 --> 00:10:22.806 especially to those of you who are naive to the effects of psychedelics, 00:10:22.806 --> 00:10:24.974 that an experience with one of these drugs 00:10:24.974 --> 00:10:28.959 can be among the most profound of the whole of your life. 00:10:28.959 --> 00:10:32.665 So evidence suggests that in terms of meaningfulness, 00:10:32.665 --> 00:10:35.437 it can be up there with pretty much anything: 00:10:35.437 --> 00:10:36.985 facing death, 00:10:37.245 --> 00:10:39.115 falling in love 00:10:39.525 --> 00:10:41.825 or bringing in new life. 00:10:42.365 --> 00:10:45.710 So the key point is that these are not party drugs; 00:10:45.710 --> 00:10:50.417 they're incredibly powerful substances that should be treated with respect, 00:10:50.417 --> 00:10:56.658 as they have been by certain cultures for hundreds, if not thousands, of years. 00:10:57.628 --> 00:11:01.427 It's also important to emphasize that when we give psilocybin to our patients, 00:11:01.427 --> 00:11:05.086 we do so with full legal and ethical approval, 00:11:05.086 --> 00:11:06.868 and we simply don't tell them 00:11:06.868 --> 00:11:12.286 to chuck a bunch of magic mushrooms down their necks and hope for the best. 00:11:12.286 --> 00:11:15.237 We carefully prepare them for their experiences. 00:11:15.237 --> 00:11:20.337 They're looked after by a trained team of therapists. 00:11:21.467 --> 00:11:23.475 They have two sessions with the psilocybin; 00:11:23.475 --> 00:11:25.538 they're looked after throughout, 00:11:25.538 --> 00:11:30.927 and the therapists help them make sense of things afterwards. 00:11:32.077 --> 00:11:34.937 So, here we can see the magnitude of the effect 00:11:34.937 --> 00:11:37.927 that we're seeing with psilocybin so far. 00:11:37.927 --> 00:11:39.275 Psilocybin is shown in blue, 00:11:39.275 --> 00:11:42.048 and you can see the data at two weeks post-treatment 00:11:42.048 --> 00:11:46.007 and three months post-treatment. 00:11:46.587 --> 00:11:49.266 Now, I should caution that it's early days yet; 00:11:49.266 --> 00:11:51.747 we had 12 patients in the trial at this stage, 00:11:51.747 --> 00:11:54.849 now, actually, we have more data and the effects look even better. 00:11:54.849 --> 00:11:58.187 But even so, there was several hundred patients in these other studies. 00:11:58.187 --> 00:12:01.747 Also, all of our patients knew that they were going to receive psilocybin 00:12:01.747 --> 00:12:05.406 whereas these other studies had a placebo-control element - 00:12:05.406 --> 00:12:08.058 that's actually what we are going to be doing next. 00:12:08.058 --> 00:12:09.746 Even so with these caveats, 00:12:09.746 --> 00:12:13.426 you can see that the magnitude of the effect that we're seeing so far 00:12:13.426 --> 00:12:15.407 is pretty considerable, 00:12:15.407 --> 00:12:17.968 even at the three-month post-treatment period 00:12:17.968 --> 00:12:23.728 where they haven't received any treatments from us for that duration of time. 00:12:24.978 --> 00:12:28.856 Also remember that our patients had treatment-resistant depression; 00:12:29.216 --> 00:12:30.828 many of our patients reported 00:12:30.828 --> 00:12:34.008 having had their depression for most of their adult lives. 00:12:34.008 --> 00:12:38.327 The average duration of the illness in this sample was 18 years, 00:12:38.327 --> 00:12:41.909 yet all of them showed some improvement in their depressive symptoms 00:12:41.909 --> 00:12:44.968 for at least three weeks after the treatment. 00:12:45.198 --> 00:12:50.855 Some two-thirds, 67%, met criteria for remission one week post treatment. 00:12:50.855 --> 00:12:54.076 Remission means they are essentially depression free. 00:12:54.076 --> 00:12:58.438 And 42% maintained that status of being depression free 00:12:58.438 --> 00:13:02.146 for three months after the treatment. 00:13:02.546 --> 00:13:06.007 So to finish, I'm just going to read you a short case report 00:13:06.007 --> 00:13:09.667 written by one of the patients in our trial. NOTE Paragraph 00:13:09.667 --> 00:13:11.295 He's male, age 52, 00:13:11.295 --> 00:13:13.878 has a very long history of depression, 00:13:13.878 --> 00:13:17.346 quite severe depression stretching back to his 20s. 00:13:17.346 --> 00:13:19.718 He's tried a number of different medications, 00:13:19.718 --> 00:13:21.688 all of which haven't worked for him, 00:13:21.688 --> 00:13:23.557 and also psychotherapy. 00:13:24.397 --> 00:13:28.236 So about his baseline state before the treatment, he says the following: 00:13:28.236 --> 00:13:30.482 "For decades, I've battled depression. 00:13:30.482 --> 00:13:33.878 The awful feeling that you don't matter, you're not making a difference, 00:13:33.878 --> 00:13:36.907 that everyone else is having a better life. 00:13:36.907 --> 00:13:42.098 The utter pointlessness of it all, getting no real enjoyment from anything." 00:13:42.738 --> 00:13:44.559 Then about the experience, he says: 00:13:44.559 --> 00:13:47.087 "There simply aren't words to describe it, 00:13:47.087 --> 00:13:51.500 but I can say that the usual negative self-narration that I have 00:13:51.500 --> 00:13:53.776 had vanished completely. 00:13:53.776 --> 00:13:56.976 It was replaced by a sense of beautiful chaos, 00:13:57.266 --> 00:14:01.428 a landscape of unimaginable color and beauty. 00:14:01.838 --> 00:14:07.416 I began to see that all of my concerns about daily living weren't relevant, 00:14:07.416 --> 00:14:11.249 that they were a result of a negative spiral. 00:14:11.859 --> 00:14:15.098 I also felt like I was learning without being taught; 00:14:15.098 --> 00:14:17.449 that intuition was being fed. 00:14:17.449 --> 00:14:20.535 The fleeting feelings from my past came back, 00:14:20.535 --> 00:14:21.975 memories too, 00:14:21.975 --> 00:14:25.148 both of which had seemed long forgotten." 00:14:26.198 --> 00:14:27.656 Then about the outcome; 00:14:27.656 --> 00:14:30.677 this was written a couple of weeks after he completed the trial. 00:14:30.677 --> 00:14:34.387 He says, "Although it's early days yet, the results are amazing. 00:14:34.387 --> 00:14:39.718 I feel more confident and calm than I have in such a long time. 00:14:39.718 --> 00:14:42.967 My outlook has changed significantly too. 00:14:42.967 --> 00:14:49.217 I'm more aware that it's pointless to get wrapped up in endless negativity. 00:14:49.657 --> 00:14:53.718 I also feel as if I've seen a much clearer picture. 00:14:53.998 --> 00:14:58.228 Another side to this is that I feel like I've had a second chance, 00:14:58.228 --> 00:15:00.226 like a survivor. 00:15:00.596 --> 00:15:02.987 I can enjoy things now the way I used to 00:15:02.987 --> 00:15:05.887 without the cynicism, without the oppression. 00:15:05.887 --> 00:15:11.725 At its most basic, I feel like I used to before the depression." 00:15:12.685 --> 00:15:15.647 If you're curious how this patient is doing in the longer term, 00:15:15.647 --> 00:15:18.319 we've collected his six-month follow-up data now; 00:15:18.319 --> 00:15:21.377 I'm pleased to say that he's still in remission. 00:15:21.377 --> 00:15:25.604 You can see his data highlighted here in blue. 00:15:25.604 --> 00:15:28.557 Of course, I've cherry-picked a particularly good example here, 00:15:28.557 --> 00:15:30.916 and you can see from other patients on this chart 00:15:30.916 --> 00:15:33.037 that at the three-month follow-up period, 00:15:33.037 --> 00:15:35.978 they're showing some signs of relapse. 00:15:35.978 --> 00:15:40.168 So this is an important opportunity to say that this isn't a magic cure; 00:15:40.168 --> 00:15:44.148 it's not a golden bullet that's going to help everyone; 00:15:44.158 --> 00:15:46.237 there's much more work that needs to be done 00:15:46.237 --> 00:15:52.514 to learn how to optimize this treatment and further test its effectiveness. 00:15:52.954 --> 00:15:56.598 But hopefully you've got a sense from that case that I reported, 00:15:56.598 --> 00:16:00.427 and I can tell you from many other cases I've sat with now 00:16:00.427 --> 00:16:02.917 that when this is done properly - 00:16:02.917 --> 00:16:05.237 with the right level of preparation, 00:16:05.667 --> 00:16:08.088 good drug effects working in synergy, 00:16:08.088 --> 00:16:09.867 with good therapy - 00:16:09.867 --> 00:16:14.628 to lift the veil on the mind and exorcise what lies beneath, 00:16:14.628 --> 00:16:17.767 it can truly work like a dream. 00:16:17.767 --> 00:16:19.097 Thank you very much. 00:16:19.097 --> 00:16:20.671 (Applause)