1 00:00:15,356 --> 00:00:24,036 Speaker 1: Pushkin. Let's talk about psychedelics. It's been a few years 2 00:00:24,116 --> 00:00:27,076 Speaker 1: since the FDA approved the use of ketamine to treat 3 00:00:27,116 --> 00:00:31,516 Speaker 1: depression in certain patients. Later this year, the FDA may 4 00:00:31,596 --> 00:00:35,236 Speaker 1: also approve the use of MDMA in combination with therapy 5 00:00:35,716 --> 00:00:40,996 Speaker 1: to treat PTSD post traumatic stress disorder, and researchers around 6 00:00:41,036 --> 00:00:45,996 Speaker 1: the world are studying other powerful psychedelics like psilocybin, ibogaine, 7 00:00:46,156 --> 00:00:49,596 Speaker 1: and LSD. It's been clear for a long time that 8 00:00:49,636 --> 00:00:53,356 Speaker 1: these are very powerful drugs, and it's becoming clear that 9 00:00:53,396 --> 00:00:57,916 Speaker 1: these drugs may be particularly helpful in certain contexts. But 10 00:00:58,356 --> 00:01:02,236 Speaker 1: still less clear is a very big, very important question, 11 00:01:03,236 --> 00:01:13,116 Speaker 1: how exactly do psychedelics work. I'm Jacob Goldstein and this 12 00:01:13,196 --> 00:01:15,276 Speaker 1: is What's Your Problem, the show where I talk to 13 00:01:15,316 --> 00:01:19,116 Speaker 1: people who are trying to make technological progress. My guest 14 00:01:19,156 --> 00:01:22,716 Speaker 1: today is goul Dolan. She's a professor of psychology and 15 00:01:22,836 --> 00:01:27,196 Speaker 1: neuroscience at the University of California at Berkeley. Goule's problem 16 00:01:27,516 --> 00:01:30,476 Speaker 1: is summed up in a phrase from a paper that 17 00:01:30,556 --> 00:01:34,196 Speaker 1: she co authored last year in the journal Nature. She's 18 00:01:34,236 --> 00:01:39,876 Speaker 1: trying to identify quote, a common neurobiological mechanism that can 19 00:01:39,916 --> 00:01:44,956 Speaker 1: account for the shared therapeutic effects of psychedelics. In other words, 20 00:01:45,276 --> 00:01:48,076 Speaker 1: why do all these very different drugs seem to have 21 00:01:48,156 --> 00:01:52,276 Speaker 1: similar powerful effects on the brain. Goole has a theory 22 00:01:52,316 --> 00:01:55,276 Speaker 1: about this, about why all these different drugs seem to 23 00:01:55,276 --> 00:01:59,236 Speaker 1: have similar effects, and if she's right, it could mean 24 00:01:59,396 --> 00:02:02,756 Speaker 1: that psychedelics used in the right context, may be useful 25 00:02:02,916 --> 00:02:07,356 Speaker 1: beyond mental illness. Goul thinks, among other things, psychedelics may 26 00:02:07,396 --> 00:02:11,596 Speaker 1: be able to help patients recod from strokes. We started 27 00:02:11,596 --> 00:02:14,556 Speaker 1: the conversation talking about the origin of Ghul's quest to 28 00:02:14,676 --> 00:02:16,556 Speaker 1: understand how psychedelics work. 29 00:02:19,156 --> 00:02:22,316 Speaker 2: About ten years ago when I started my lab, you know, 30 00:02:22,396 --> 00:02:25,596 Speaker 2: there were starting to be some hints that psychedelics were 31 00:02:25,596 --> 00:02:28,916 Speaker 2: having these remarkable effects in you know, all kinds of 32 00:02:28,956 --> 00:02:32,036 Speaker 2: diseases that didn't seem terribly connected to each other, right, 33 00:02:32,116 --> 00:02:36,916 Speaker 2: so addiction and depression and PTSD, and you know, the 34 00:02:36,956 --> 00:02:39,876 Speaker 2: people who study those diseases each have their way of 35 00:02:39,916 --> 00:02:43,756 Speaker 2: studying them and modeling them in animals, and they're they're 36 00:02:43,796 --> 00:02:47,036 Speaker 2: siloed into different spaces. And yet we were starting to 37 00:02:47,116 --> 00:02:51,476 Speaker 2: hear hints that, you know, it didn't matter which psychedelic 38 00:02:51,556 --> 00:02:55,076 Speaker 2: they were kind of interchangeably showing some promise in all 39 00:02:55,116 --> 00:02:58,836 Speaker 2: of these different areas that seem unconnected to each other. 40 00:02:58,916 --> 00:03:01,996 Speaker 2: I mean not just in terms of what behavioral essays 41 00:03:01,996 --> 00:03:04,236 Speaker 2: we use, but even sort of what brain regions might 42 00:03:04,236 --> 00:03:07,956 Speaker 2: be important. Right, Like, the depression people were focused on 43 00:03:07,996 --> 00:03:10,156 Speaker 2: the hippi campus and the frontal cortex. 44 00:03:10,276 --> 00:03:11,836 Speaker 3: The PTSD people. 45 00:03:11,676 --> 00:03:15,956 Speaker 2: Were focused on the amygdala, the you know, the addiction 46 00:03:15,996 --> 00:03:18,236 Speaker 2: people were focused on the nucleus, thecumbents, and they were 47 00:03:18,236 --> 00:03:20,516 Speaker 2: just sort of all over the place, and yet there 48 00:03:20,516 --> 00:03:24,956 Speaker 2: seemed to be this overlap. But when we then discovered 49 00:03:25,036 --> 00:03:27,196 Speaker 2: that all of the psychedelics seemed to be doing the 50 00:03:27,316 --> 00:03:31,076 Speaker 2: same thing, it sort of began to settle in that 51 00:03:31,676 --> 00:03:35,276 Speaker 2: this explanation that we came up with could account for 52 00:03:35,836 --> 00:03:38,436 Speaker 2: why all of these diseases that look so different from 53 00:03:38,436 --> 00:03:43,436 Speaker 2: each other could be responding to psychedelics in a therapeutic way. 54 00:03:43,996 --> 00:03:48,596 Speaker 1: So should we start the explanation with talking about critical periods? 55 00:03:48,676 --> 00:03:50,876 Speaker 1: Is that a reasonable place to start. Let's start with 56 00:03:50,876 --> 00:03:52,396 Speaker 1: critical periods. What's the critical period? 57 00:03:52,956 --> 00:03:53,156 Speaker 3: Right? 58 00:03:53,196 --> 00:03:56,796 Speaker 2: So, critical periods are something that you know, neuroscientists have 59 00:03:56,996 --> 00:03:59,716 Speaker 2: known about for almost one hundred years. They were first 60 00:03:59,756 --> 00:04:03,916 Speaker 2: described in nineteen thirty five by Conrad Lorenz, who was 61 00:04:03,996 --> 00:04:09,916 Speaker 2: describing and imprinting behavior in baby geese, So basically, forty 62 00:04:09,916 --> 00:04:12,636 Speaker 2: eight hours after they hatch from their eggs, they will 63 00:04:12,996 --> 00:04:17,116 Speaker 2: imprint onto anything that is moving around in their immediate environment. 64 00:04:17,236 --> 00:04:20,076 Speaker 2: So typically this would be their mother, but you know, 65 00:04:20,076 --> 00:04:22,356 Speaker 2: if there's a crazy scientist around, it might be to 66 00:04:22,436 --> 00:04:23,436 Speaker 2: the crazy scientist. 67 00:04:23,596 --> 00:04:27,036 Speaker 1: And there are photos of the baby geese following him 68 00:04:27,036 --> 00:04:29,836 Speaker 1: around right in fact, as if he were a mamma goose. 69 00:04:29,916 --> 00:04:31,396 Speaker 4: Yeah, exactly. 70 00:04:31,476 --> 00:04:34,156 Speaker 2: And so but that window of time where they're so 71 00:04:34,356 --> 00:04:37,636 Speaker 2: sensitive to their environment and they form these lasting attachments 72 00:04:38,036 --> 00:04:41,036 Speaker 2: only lasts about forty eight hours, and then afterwards they don't. 73 00:04:41,236 --> 00:04:43,356 Speaker 2: They're not sensitive to their environment in the same way. 74 00:04:43,556 --> 00:04:45,676 Speaker 2: They're not learning from their environment in the same way. 75 00:04:45,716 --> 00:04:48,836 Speaker 2: And that window of time Conrad Lorenz called it the 76 00:04:48,836 --> 00:04:53,716 Speaker 2: critical period. And since that time we've discovered literally dozens 77 00:04:53,756 --> 00:04:56,836 Speaker 2: of other critical periods. So there are critical periods for 78 00:04:56,956 --> 00:05:01,596 Speaker 2: rewiring the visual system, critical periods for touch, critical periods 79 00:05:01,636 --> 00:05:05,596 Speaker 2: for movement, critical periods for language. Language is probably the 80 00:05:05,596 --> 00:05:07,996 Speaker 2: one that most people are familiar with. If they try 81 00:05:08,036 --> 00:05:11,356 Speaker 2: to learn enough their language when they were older, it's 82 00:05:11,436 --> 00:05:13,916 Speaker 2: much harder and you always have an accent compared to 83 00:05:13,956 --> 00:05:17,796 Speaker 2: the language you learn as a child, and so neuroscientists 84 00:05:17,836 --> 00:05:20,756 Speaker 2: have known about these critical periods for a long time, 85 00:05:21,436 --> 00:05:25,396 Speaker 2: and we've had this idea that maybe the reason that 86 00:05:25,476 --> 00:05:29,516 Speaker 2: we're so bad at curing diseases of the brain, neuropsychiatric 87 00:05:29,556 --> 00:05:33,436 Speaker 2: illnesses and neurological diseases, is because by the time we 88 00:05:33,516 --> 00:05:38,516 Speaker 2: get around to correcting whatever is the underlying problem, the 89 00:05:38,636 --> 00:05:40,316 Speaker 2: relevant critical period. 90 00:05:39,996 --> 00:05:40,996 Speaker 3: Has already closed. 91 00:05:41,436 --> 00:05:44,396 Speaker 2: And so the classic example of this is if you 92 00:05:44,516 --> 00:05:47,796 Speaker 2: are born with bilateral cataracts in your eyes and you 93 00:05:47,876 --> 00:05:50,596 Speaker 2: don't have them removed by the time you're aged five 94 00:05:50,716 --> 00:05:53,916 Speaker 2: or so, then you will be blind forever because even 95 00:05:53,996 --> 00:05:57,196 Speaker 2: if you remove the cataracts, wants the ability of the 96 00:05:57,316 --> 00:06:01,116 Speaker 2: visual part of the brain to adapt to the corrected 97 00:06:01,236 --> 00:06:04,756 Speaker 2: visual environment. Once the critical period has closed, it can't 98 00:06:04,796 --> 00:06:07,996 Speaker 2: adapt again, and so even though the impediment is removed, 99 00:06:08,476 --> 00:06:11,276 Speaker 2: the brain can respond to it, and so you're blind forever. 100 00:06:12,596 --> 00:06:15,916 Speaker 2: And so we have been looking, probably for the last 101 00:06:15,916 --> 00:06:19,716 Speaker 2: one hundred years or so for ways to reopen critical periods, 102 00:06:19,716 --> 00:06:22,756 Speaker 2: with the idea that if we could reopen them, we 103 00:06:22,836 --> 00:06:27,036 Speaker 2: could potentially cure or do a better job of correcting 104 00:06:27,036 --> 00:06:29,036 Speaker 2: some of these impairments later in life. 105 00:06:29,556 --> 00:06:32,916 Speaker 1: So in this Nature paper, that you published last year. 106 00:06:33,396 --> 00:06:38,436 Speaker 1: You write, it's tempting to speculate that the altered state 107 00:06:38,716 --> 00:06:43,796 Speaker 1: of consciousness shared by all psychedelics reflects the subjective experience 108 00:06:43,956 --> 00:06:47,476 Speaker 1: of reopening critical periods. Let me say, first of all, 109 00:06:47,516 --> 00:06:50,156 Speaker 1: I like, it's tempting to speculate. It's like, you're not 110 00:06:50,236 --> 00:06:51,156 Speaker 1: even speculating. 111 00:06:51,196 --> 00:06:54,436 Speaker 5: It's more speculative than speculating, right, Like, we're not going 112 00:06:54,516 --> 00:06:58,596 Speaker 5: to speculate, but we're tempted to speculate. So and I 113 00:06:58,636 --> 00:07:01,236 Speaker 5: appreciate that, right, Like, this is clearly speculative, it's based 114 00:07:01,276 --> 00:07:04,316 Speaker 5: on research and mice. But why are you tempted to 115 00:07:04,356 --> 00:07:09,116 Speaker 5: speculate that psychedelics may reopen critical periods in the brain? 116 00:07:09,996 --> 00:07:10,196 Speaker 3: Right? 117 00:07:10,516 --> 00:07:14,996 Speaker 2: So, the reason that we're tempted to speculate this is because, 118 00:07:16,196 --> 00:07:19,356 Speaker 2: you know, one of the other things that brings together 119 00:07:19,396 --> 00:07:23,236 Speaker 2: psychedelics as a group of drugs is that they all 120 00:07:23,276 --> 00:07:26,556 Speaker 2: induced this altered state of consciousness. So we discovered a 121 00:07:26,556 --> 00:07:30,756 Speaker 2: critical period in twenty nineteen for Social rewards learning. It 122 00:07:30,796 --> 00:07:33,596 Speaker 2: was a brand new critical period. Although you know, there 123 00:07:33,676 --> 00:07:37,556 Speaker 2: was a lot of literature from human studies suggesting that 124 00:07:37,596 --> 00:07:40,876 Speaker 2: such a critical period should exist, but it just took 125 00:07:40,996 --> 00:07:43,156 Speaker 2: doing it. In nine hundred mice to be able to 126 00:07:43,156 --> 00:07:46,396 Speaker 2: formally demonstrate it. So we did that. We showed that 127 00:07:46,436 --> 00:07:49,956 Speaker 2: there's this social critical period, and originally we showed that 128 00:07:50,156 --> 00:07:53,196 Speaker 2: MDMA was able to reopen this critical period. And we 129 00:07:53,276 --> 00:07:58,716 Speaker 2: thought because MDMA is characterized by having this pro social 130 00:07:58,836 --> 00:08:02,396 Speaker 2: property that makes it different from the other psychedelics in that, 131 00:08:02,796 --> 00:08:06,156 Speaker 2: you know, it's altered state of consciousness, plus you know, 132 00:08:06,236 --> 00:08:09,956 Speaker 2: cuddle puddles and empathy, right, and so we thought it's 133 00:08:09,996 --> 00:08:13,516 Speaker 2: because of that pro social property of MDMA that it's 134 00:08:13,556 --> 00:08:17,156 Speaker 2: able to open this social critical period. But then when 135 00:08:17,156 --> 00:08:21,556 Speaker 2: we figured out that well LSD and I began and KETYMI, 136 00:08:21,676 --> 00:08:24,996 Speaker 2: none of which are like particularly pro social, nobody's you know, 137 00:08:25,076 --> 00:08:27,876 Speaker 2: doing a thirty person cuddle puddle on I begin right, 138 00:08:28,716 --> 00:08:31,316 Speaker 2: even though they don't have this pro social property, they 139 00:08:31,316 --> 00:08:33,116 Speaker 2: are all also able. 140 00:08:32,836 --> 00:08:34,676 Speaker 3: To open this critical period. 141 00:08:34,716 --> 00:08:38,116 Speaker 2: And so that was our first hint that maybe the 142 00:08:38,756 --> 00:08:45,516 Speaker 2: common property is between psychedelics that accounts for this altered 143 00:08:45,556 --> 00:08:48,716 Speaker 2: state of consciousness that they all induce is the common 144 00:08:48,756 --> 00:08:51,996 Speaker 2: property of inducing critical period reopening. 145 00:08:52,316 --> 00:08:56,036 Speaker 1: And so specifically, can you just talk a little bit 146 00:08:56,036 --> 00:08:59,596 Speaker 1: more about the specific critical period in mice that you're 147 00:08:59,636 --> 00:09:01,556 Speaker 1: looking at here, right? 148 00:09:01,596 --> 00:09:05,916 Speaker 2: So, we're measuring something called social condition place preference, which 149 00:09:05,956 --> 00:09:09,956 Speaker 2: is just an assay to measure the ability of the 150 00:09:10,036 --> 00:09:13,956 Speaker 2: mice to learn from their social environments. And so that 151 00:09:14,276 --> 00:09:18,036 Speaker 2: ability changes over time, and as they get older, they 152 00:09:18,036 --> 00:09:21,956 Speaker 2: stop learning from their social environment. And so this developmental 153 00:09:22,036 --> 00:09:25,276 Speaker 2: change relates to why we think teenagers are so much 154 00:09:25,316 --> 00:09:28,596 Speaker 2: more susceptible to peer pressure than adults. We think it 155 00:09:28,636 --> 00:09:32,196 Speaker 2: relates to why you're so much more sensitive to learning 156 00:09:32,316 --> 00:09:35,596 Speaker 2: the rules of your culture when you're young, so you know, 157 00:09:35,716 --> 00:09:36,956 Speaker 2: you learn what's polite. 158 00:09:37,396 --> 00:09:40,156 Speaker 1: So it's basically the idea is that there's a critical 159 00:09:40,316 --> 00:09:44,236 Speaker 1: there is some set of critical periods for learning social 160 00:09:44,516 --> 00:09:50,476 Speaker 1: behavior from language to norms, and that that those clothes 161 00:09:50,676 --> 00:09:53,516 Speaker 1: over the course of childhood and adolescents. 162 00:09:53,796 --> 00:09:54,596 Speaker 3: That's right, that's right. 163 00:09:55,516 --> 00:10:00,196 Speaker 2: And we think that that critical period, like other critical 164 00:10:00,236 --> 00:10:04,236 Speaker 2: periods like language, you know, is curtailed as you get 165 00:10:04,276 --> 00:10:10,636 Speaker 2: older because basically it's sort of expensive energe to always 166 00:10:10,676 --> 00:10:13,316 Speaker 2: be having to learn from your social environment. 167 00:10:13,476 --> 00:10:14,436 Speaker 3: You know, I like to. 168 00:10:15,876 --> 00:10:18,716 Speaker 2: Think back on my teenage years and you know, mostly 169 00:10:18,716 --> 00:10:21,716 Speaker 2: I'm relieved that they're over, because you know, it was 170 00:10:21,996 --> 00:10:26,836 Speaker 2: time consuming and energetically exhausting to you know, have to 171 00:10:26,876 --> 00:10:29,636 Speaker 2: care about the exact right shade of acid washed genes 172 00:10:29,676 --> 00:10:30,796 Speaker 2: that the cool kids are wearing. 173 00:10:30,876 --> 00:10:33,956 Speaker 1: Right, and now you wear whatever acid wash genes you want, right, 174 00:10:34,076 --> 00:10:34,596 Speaker 1: that's right. 175 00:10:34,716 --> 00:10:37,396 Speaker 4: I wear mom jeans that are acid washed. 176 00:10:39,636 --> 00:10:43,556 Speaker 1: And so then you find that when you give psychedelics 177 00:10:43,596 --> 00:10:46,996 Speaker 1: to an old mouse, they're able to the. 178 00:10:47,036 --> 00:10:51,076 Speaker 2: Learning that they were doing in juvenile in their juvenile 179 00:10:51,116 --> 00:10:54,676 Speaker 2: period return, so they're able to learn again like a juvenile. 180 00:10:55,396 --> 00:10:59,036 Speaker 1: Have you tested this theory on other critical periods in 181 00:10:59,116 --> 00:11:01,116 Speaker 1: mice or on other animals? 182 00:11:01,596 --> 00:11:05,316 Speaker 2: Yeah, So basically, as soon as we got this this result, 183 00:11:05,516 --> 00:11:07,956 Speaker 2: I reached out to every single person that I know 184 00:11:08,156 --> 00:11:10,236 Speaker 2: who works on critics periods, and I was like, do 185 00:11:10,236 --> 00:11:13,436 Speaker 2: you have a critical period that you want to try 186 00:11:13,436 --> 00:11:16,396 Speaker 2: and reopen? Because I think we might have accidentally stumbled 187 00:11:16,396 --> 00:11:20,076 Speaker 2: on the master key for unlocking critical periods, and so 188 00:11:20,196 --> 00:11:23,836 Speaker 2: we're working on it. We definitely have some collaborations going. 189 00:11:24,476 --> 00:11:27,476 Speaker 2: But in the meantime between sort of when we first 190 00:11:27,556 --> 00:11:30,876 Speaker 2: have this twenty nineteen paper and then this summer, there 191 00:11:30,916 --> 00:11:35,916 Speaker 2: have been some hints that other critical periods are being 192 00:11:35,956 --> 00:11:40,756 Speaker 2: reopened by say ketamine. There are two papers showing that ketamine, 193 00:11:40,796 --> 00:11:43,196 Speaker 2: if given back to back to back to back can 194 00:11:43,236 --> 00:11:47,156 Speaker 2: reopen the critical period for ocular dominance plasticity, which is 195 00:11:47,196 --> 00:11:51,076 Speaker 2: this visual critical period that we've learned so much about 196 00:11:51,076 --> 00:11:54,796 Speaker 2: the mechanisms about. So that's a first hint, and we 197 00:11:54,836 --> 00:11:59,156 Speaker 2: are working feverishly to see if we can reopen other 198 00:11:59,236 --> 00:12:02,996 Speaker 2: critical periods like motor learning for stroke. We're doing that 199 00:12:03,036 --> 00:12:06,436 Speaker 2: in both mice and in humans. We're working on some 200 00:12:06,556 --> 00:12:09,836 Speaker 2: language critical periods in collaboration with some of the labs. 201 00:12:09,956 --> 00:12:13,636 Speaker 2: So you know, the jury is still out, but there's 202 00:12:13,676 --> 00:12:15,956 Speaker 2: some other reasons to make us think that we're on 203 00:12:16,036 --> 00:12:19,436 Speaker 2: the right track with this idea about the master key. 204 00:12:20,036 --> 00:12:23,396 Speaker 1: When you say master key in this context, in this context, 205 00:12:23,396 --> 00:12:24,316 Speaker 1: exactly what do you mean? 206 00:12:25,316 --> 00:12:28,036 Speaker 2: So I guess what I mean is is that when 207 00:12:28,076 --> 00:12:30,796 Speaker 2: I was a graduate student, we were a little bit 208 00:12:30,796 --> 00:12:34,356 Speaker 2: in a debate with another lab that was proposing that 209 00:12:34,396 --> 00:12:38,596 Speaker 2: there would be some drug or manipulation that you could 210 00:12:38,596 --> 00:12:43,356 Speaker 2: do that could reopen all critical periods, and that you 211 00:12:43,436 --> 00:12:47,916 Speaker 2: could just give that drug and it would it would 212 00:12:48,516 --> 00:12:50,916 Speaker 2: it would be the master key, right and for unlocking 213 00:12:50,956 --> 00:12:53,796 Speaker 2: all of these critical periods. And at the time, I 214 00:12:53,876 --> 00:12:58,516 Speaker 2: remember being really skeptical of that idea, and I thought, well, 215 00:12:58,556 --> 00:13:01,636 Speaker 2: anything that can do that to the brain is either 216 00:13:01,756 --> 00:13:07,516 Speaker 2: going to induce amnesia, cause seizure, or disrupt the structural 217 00:13:07,996 --> 00:13:11,196 Speaker 2: integrity of the brain. And I thought that because of 218 00:13:11,236 --> 00:13:14,556 Speaker 2: what we knew about, you know, basically the mechanisms that 219 00:13:14,676 --> 00:13:19,356 Speaker 2: constrain critical periods to these windows of time, like like. 220 00:13:19,276 --> 00:13:22,036 Speaker 1: You couldn't work without breaking the brain. The only way 221 00:13:22,116 --> 00:13:24,756 Speaker 1: to reopen the critical period is the master key is 222 00:13:24,796 --> 00:13:27,676 Speaker 1: like a sledgehammer that's just gonna totally break everything. So 223 00:13:27,756 --> 00:13:28,716 Speaker 1: why even bother. 224 00:13:29,196 --> 00:13:31,396 Speaker 2: Right, And I you know, I called it the Melti 225 00:13:31,436 --> 00:13:34,316 Speaker 2: brain problem, right, And so then when we when we 226 00:13:34,396 --> 00:13:39,676 Speaker 2: started getting these results for the psychedelics, I was, I 227 00:13:39,716 --> 00:13:42,436 Speaker 2: started thinking, well, how come we're not running into the 228 00:13:42,436 --> 00:13:46,276 Speaker 2: Melty brain problem? And I think, and this is at 229 00:13:46,276 --> 00:13:50,716 Speaker 2: this point still speculative, and we're we're actively pursuing this 230 00:13:50,836 --> 00:13:53,556 Speaker 2: line of research. So I don't want to overstate the case. 231 00:13:53,876 --> 00:13:56,876 Speaker 2: But my hunch is that the way that we are 232 00:13:56,916 --> 00:14:01,476 Speaker 2: able to circumvent, or the way that psychedelics specifically are circumventing, 233 00:14:01,916 --> 00:14:06,756 Speaker 2: the Melty brain problem is that they are context specific. 234 00:14:07,236 --> 00:14:12,636 Speaker 2: So it's not that psychdelics are causing reopening of all 235 00:14:12,676 --> 00:14:16,676 Speaker 2: critical periods everywhere in the brain all at the same time. 236 00:14:17,076 --> 00:14:21,556 Speaker 2: It seems to be that they are not you know, 237 00:14:21,636 --> 00:14:26,276 Speaker 2: destroying or melting the brain, because they're only making available 238 00:14:26,476 --> 00:14:34,436 Speaker 2: for modification the subset of synapses, circuits, memories, and grams 239 00:14:34,596 --> 00:14:38,316 Speaker 2: that are have been recently activated, and that is why 240 00:14:38,636 --> 00:14:41,436 Speaker 2: they have this constraint of being context dependent. 241 00:14:42,316 --> 00:14:45,476 Speaker 1: So this is this is why your thesis is they 242 00:14:45,556 --> 00:14:51,076 Speaker 1: will psychedels will be helpful when paired with interventions like therapy, 243 00:14:51,516 --> 00:14:53,316 Speaker 1: but not by themselves. 244 00:14:53,756 --> 00:14:54,756 Speaker 4: Well, this is. 245 00:14:56,436 --> 00:15:00,596 Speaker 2: This is the explanation we have for why the psychedelics 246 00:15:00,596 --> 00:15:06,236 Speaker 2: aren't breaking the the brain rather than I mean, basically, 247 00:15:06,276 --> 00:15:11,276 Speaker 2: the clinical data is driving this idea that in fact 248 00:15:11,396 --> 00:15:13,076 Speaker 2: the context matters, right. 249 00:15:12,996 --> 00:15:15,996 Speaker 1: But it's a potential mechanistic explanation for that. 250 00:15:15,996 --> 00:15:19,076 Speaker 2: Clinical well that feature, that's right, it's a mechanistic explanation 251 00:15:19,116 --> 00:15:22,276 Speaker 2: for a clinical description, which you know, I don't think 252 00:15:22,436 --> 00:15:24,716 Speaker 2: is going to be the case for every single application 253 00:15:24,796 --> 00:15:27,676 Speaker 2: that psychedelics might be used for. So, for example, I 254 00:15:27,716 --> 00:15:32,796 Speaker 2: think the critical period idea nicely explains why MDMA assisted 255 00:15:32,836 --> 00:15:37,596 Speaker 2: psychotherapy works. If we're able to demonstrate that we can 256 00:15:37,716 --> 00:15:44,916 Speaker 2: correct motor impairments following stroke with psychedelics paired with physical therapy, 257 00:15:44,956 --> 00:15:47,036 Speaker 2: then that'll be a nice other explanation. 258 00:15:47,676 --> 00:15:50,796 Speaker 1: That's a huge idea. You've just dropped in the middle 259 00:15:50,836 --> 00:15:52,236 Speaker 1: of a list, by the. 260 00:15:52,196 --> 00:15:55,996 Speaker 2: Way, right, So, by the way, that's also quite quite speculative. 261 00:16:00,756 --> 00:16:04,316 Speaker 1: After the break, how gool plans to test this hypothesis 262 00:16:04,716 --> 00:16:19,436 Speaker 1: that psychedelics may help patients recovering from strokes. Let's just 263 00:16:19,556 --> 00:16:22,556 Speaker 1: talk about how we get from this sort of you know, 264 00:16:23,596 --> 00:16:28,716 Speaker 1: seems like psychedelics reopen one critical period in mice to like, 265 00:16:29,836 --> 00:16:31,796 Speaker 1: can this idea be helpful in humans? 266 00:16:31,916 --> 00:16:32,076 Speaker 4: Right? 267 00:16:33,836 --> 00:16:36,756 Speaker 1: You must know the aphorism mice lie and primates exaggerate. 268 00:16:36,836 --> 00:16:38,196 Speaker 1: I was thinking of that one. 269 00:16:39,716 --> 00:16:42,116 Speaker 2: I mean, I think that a little bit of why 270 00:16:42,156 --> 00:16:46,436 Speaker 2: it's so hard to translate this stuff from mouse studies 271 00:16:46,436 --> 00:16:50,356 Speaker 2: to human studies so far is that mostly what they've 272 00:16:50,356 --> 00:16:54,636 Speaker 2: been used for is non psychiatric disease, and so it's 273 00:16:54,716 --> 00:17:00,636 Speaker 2: really sort of impossible to measure or to recapitulate all 274 00:17:00,636 --> 00:17:03,476 Speaker 2: of the features of a psychiatric disease. 275 00:17:03,116 --> 00:17:05,036 Speaker 3: In a mouse. Right, Like if. 276 00:17:04,956 --> 00:17:08,956 Speaker 2: PTSD is mostly in humans and females is caused by 277 00:17:09,396 --> 00:17:12,396 Speaker 2: you can't really model rape in a mouse, right, And 278 00:17:12,436 --> 00:17:15,676 Speaker 2: so there are all these other features of the illness 279 00:17:15,836 --> 00:17:18,956 Speaker 2: that you know, you can try and approximate by fear learning, 280 00:17:18,996 --> 00:17:21,956 Speaker 2: but you're not really going to capture the salient elements. 281 00:17:22,196 --> 00:17:26,036 Speaker 2: And so this is kind of why I think an 282 00:17:26,036 --> 00:17:29,796 Speaker 2: important test case of this idea of the master key 283 00:17:30,356 --> 00:17:34,756 Speaker 2: is to switch away from neuropsychiatric disease and move into 284 00:17:34,836 --> 00:17:40,276 Speaker 2: neurological disease, because then you know, we can explicitly test 285 00:17:40,356 --> 00:17:43,716 Speaker 2: this learning model. Right if we switch to a neurological 286 00:17:43,756 --> 00:17:47,876 Speaker 2: disease like stroke, and we're able to show that if 287 00:17:47,916 --> 00:17:51,156 Speaker 2: we give psychedelics and pair it with physical therapy, we 288 00:17:51,196 --> 00:17:55,756 Speaker 2: are able to restore motor learning. But if we give 289 00:17:55,756 --> 00:17:59,196 Speaker 2: psychedelics and then just send them on home without any 290 00:17:59,196 --> 00:18:02,356 Speaker 2: additional physical therapy, then nothing really is going to happen. 291 00:18:02,876 --> 00:18:05,276 Speaker 2: That I think would be an explicit test of this 292 00:18:05,436 --> 00:18:09,596 Speaker 2: idea that what the mechanism at work here is about 293 00:18:09,676 --> 00:18:12,796 Speaker 2: learning and memory rather than a magic bill that corrects 294 00:18:12,796 --> 00:18:14,636 Speaker 2: an underlying biochemical imbalance. 295 00:18:15,236 --> 00:18:17,356 Speaker 1: Well, yes, I mean that's the side of it, addressing 296 00:18:17,676 --> 00:18:21,716 Speaker 1: this debate that you're involved in, but also going on 297 00:18:21,796 --> 00:18:23,876 Speaker 1: there presumably if you're able to do this test in 298 00:18:23,916 --> 00:18:29,276 Speaker 1: stroke patients, is if psychedelics plus physical therapy after a 299 00:18:29,316 --> 00:18:33,836 Speaker 1: stroke leads to better recovery than physical therapy alone. That's great. 300 00:18:33,916 --> 00:18:35,796 Speaker 1: I mean, I don't even care about the mechanism at 301 00:18:35,836 --> 00:18:38,316 Speaker 1: that point, right, Like, is somebody going to do a 302 00:18:38,356 --> 00:18:42,156 Speaker 1: phase one safety trial soon? Like is somebody going to 303 00:18:42,156 --> 00:18:43,836 Speaker 1: give stroke patients psychedelics? 304 00:18:44,516 --> 00:18:45,796 Speaker 4: We are, we are working on it. 305 00:18:46,116 --> 00:18:48,196 Speaker 2: Right after this call, I have a meeting to try 306 00:18:48,236 --> 00:18:52,076 Speaker 2: and secure funding to make that happen. So we are 307 00:18:52,076 --> 00:18:54,316 Speaker 2: on it, and we are actually doing it in parallel 308 00:18:54,396 --> 00:18:58,116 Speaker 2: with mouth studies for mechanism. And you know, I understand 309 00:18:58,196 --> 00:19:01,036 Speaker 2: why people are so much more jazzed about you know 310 00:19:01,116 --> 00:19:04,876 Speaker 2: the clinical outcomes and you know the real world impacts 311 00:19:04,876 --> 00:19:07,796 Speaker 2: of these things. But I have to say, I think 312 00:19:08,276 --> 00:19:12,236 Speaker 2: mechanism should not be underestimated as an important way of 313 00:19:12,356 --> 00:19:14,876 Speaker 2: understanding this, because we never would have even come up 314 00:19:14,916 --> 00:19:18,436 Speaker 2: with this idea of thinking about stroke if we hadn't 315 00:19:18,476 --> 00:19:21,716 Speaker 2: thought of the mechanism. Right, So, if we the mechanism 316 00:19:21,996 --> 00:19:26,276 Speaker 2: is what is leading us to speculate, if this mechanism 317 00:19:26,396 --> 00:19:30,076 Speaker 2: is true, then these other diseases should respond in this 318 00:19:30,276 --> 00:19:31,236 Speaker 2: predictable way. 319 00:19:31,636 --> 00:19:33,796 Speaker 1: There was a better way I could have framed that, 320 00:19:34,756 --> 00:19:37,636 Speaker 1: And I apologize. I mean, what I really mean is, yes, 321 00:19:37,716 --> 00:19:40,796 Speaker 1: it's it's useful and big to learn the mechanism. But 322 00:19:40,996 --> 00:19:44,916 Speaker 1: like helping stroke patients get better is also a huge deal. 323 00:19:45,196 --> 00:19:48,356 Speaker 1: Would perhaps be diplomatic way to say that. 324 00:19:48,716 --> 00:19:51,676 Speaker 2: I mean, I don't mind the undiplomatic way, because that's 325 00:19:51,796 --> 00:19:53,556 Speaker 2: I've been dealing with this right from the beginning. 326 00:19:53,636 --> 00:19:53,796 Speaker 4: Right. 327 00:19:53,836 --> 00:19:57,116 Speaker 2: So, the first time I presented this critical period idea 328 00:19:57,156 --> 00:19:59,716 Speaker 2: at a meeting, it was in Portugal, and you know, 329 00:19:59,756 --> 00:20:03,196 Speaker 2: the room was full of people who were already doing 330 00:20:03,756 --> 00:20:08,876 Speaker 2: clinical trials for psilocybin for depression and MDMA for PTSD, 331 00:20:09,156 --> 00:20:11,836 Speaker 2: and they were already very much invested in the idea 332 00:20:11,916 --> 00:20:14,596 Speaker 2: that it was going to work based on some underground 333 00:20:14,676 --> 00:20:18,876 Speaker 2: therapists results and anecdotal reports, some of their you know, 334 00:20:19,516 --> 00:20:22,596 Speaker 2: pilot studies, and they were like, why do we need mechanism? 335 00:20:22,636 --> 00:20:23,156 Speaker 4: Who cares? 336 00:20:23,236 --> 00:20:25,916 Speaker 2: We know it's going to work, and going backwards to 337 00:20:26,036 --> 00:20:27,396 Speaker 2: look in mice seems silly. 338 00:20:27,476 --> 00:20:29,116 Speaker 4: We know it's going to work. It's just the way 339 00:20:29,196 --> 00:20:29,556 Speaker 4: to die. 340 00:20:30,036 --> 00:20:32,956 Speaker 2: And I said at that time it was like, mechanism matters, 341 00:20:33,036 --> 00:20:35,276 Speaker 2: and there are going to be a million different ways 342 00:20:35,276 --> 00:20:38,716 Speaker 2: that we might fail if we don't understand exactly how 343 00:20:38,756 --> 00:20:42,396 Speaker 2: these drugs are working. And basically that prediction ended up 344 00:20:42,436 --> 00:20:45,196 Speaker 2: being true because the two people who were represented in 345 00:20:45,276 --> 00:20:48,796 Speaker 2: that room were on the one side, the people arguing for, 346 00:20:49,196 --> 00:20:52,636 Speaker 2: you know, let's just use psilocybin like a next generation SSRI, 347 00:20:53,196 --> 00:20:55,836 Speaker 2: and their trial failed. And then the other half of 348 00:20:55,876 --> 00:20:57,876 Speaker 2: the room where people who were saying, no, we need 349 00:20:57,916 --> 00:21:01,636 Speaker 2: to pair it with psychotherapy, and their trial was successful. 350 00:21:01,676 --> 00:21:05,396 Speaker 2: And our mechanism, we think explains the difference between them. 351 00:21:06,396 --> 00:21:09,596 Speaker 1: Is there an animal model you can use is to 352 00:21:09,756 --> 00:21:16,356 Speaker 1: test your hypothesis that in stroke patients psychedelics plus physical 353 00:21:16,356 --> 00:21:19,356 Speaker 1: therapy would work better than physical therapy alone. 354 00:21:20,116 --> 00:21:22,556 Speaker 2: Yes, So basically, one of the people I reached out 355 00:21:22,596 --> 00:21:25,636 Speaker 2: to when you know, we first got this critical period 356 00:21:25,756 --> 00:21:30,236 Speaker 2: result for all of the psychedelics. We're two neurologists at 357 00:21:30,316 --> 00:21:34,236 Speaker 2: John Hopkins, so Steve Zeiler and John Krackauer, and Steve 358 00:21:34,276 --> 00:21:39,076 Speaker 2: Zyler especially had been working on developing a mouse model 359 00:21:39,236 --> 00:21:43,596 Speaker 2: of stroke. And what he has shown is that just 360 00:21:43,716 --> 00:21:46,676 Speaker 2: like in human patients with stroke, right after the stroke, 361 00:21:47,156 --> 00:21:50,716 Speaker 2: there is a critical period that gets reopened and some 362 00:21:50,836 --> 00:21:55,036 Speaker 2: amount of physical therapy is able to restore function, but 363 00:21:55,196 --> 00:21:58,516 Speaker 2: that that is time limited. So in my you know, 364 00:21:58,716 --> 00:22:01,676 Speaker 2: within seven days after the stroke, they're no longer able 365 00:22:01,716 --> 00:22:04,436 Speaker 2: to learn. In humans that's a little bit longer. So 366 00:22:04,996 --> 00:22:07,276 Speaker 2: you know, in humans. After your stroke, you're able to 367 00:22:07,436 --> 00:22:10,796 Speaker 2: benefit from therap physical therapy for about two months. At 368 00:22:10,836 --> 00:22:14,836 Speaker 2: about three months it goes away, and that window of time, 369 00:22:15,396 --> 00:22:18,276 Speaker 2: you know, it's closure. And people have thought about, well, 370 00:22:18,436 --> 00:22:20,596 Speaker 2: you know, nobody has dreamed big that we might be 371 00:22:20,596 --> 00:22:23,436 Speaker 2: able to reopen it. But people have tried to do 372 00:22:23,556 --> 00:22:26,836 Speaker 2: other manipulations that might keep it open longer, you know, 373 00:22:26,916 --> 00:22:30,716 Speaker 2: by enriching the environment, by you know, giving them SSRIs, 374 00:22:30,956 --> 00:22:32,276 Speaker 2: and none of those things have worked. 375 00:22:32,796 --> 00:22:36,436 Speaker 1: It's the injury of the stroke itself is inducing the 376 00:22:36,476 --> 00:22:39,636 Speaker 1: brain to reopen the critical period that has been closed 377 00:22:39,636 --> 00:22:43,676 Speaker 1: since childhood, and that allows people to whatever, try and 378 00:22:43,716 --> 00:22:46,836 Speaker 1: relearn language, try and relearn motor skills whatever they have 379 00:22:46,996 --> 00:22:50,156 Speaker 1: lost in the stroke. Obviously not always successfully. 380 00:22:50,076 --> 00:22:50,556 Speaker 3: That's right. 381 00:22:50,596 --> 00:22:54,916 Speaker 2: And basically until this this psychedelic idea came around, the 382 00:22:54,956 --> 00:22:58,276 Speaker 2: most effective way to reopen the critical period for motor 383 00:22:58,356 --> 00:23:01,796 Speaker 2: learning after stroke was to give another stroke, which is 384 00:23:01,836 --> 00:23:05,556 Speaker 2: not you know, very therapeutically viable, right Like, nobody wants 385 00:23:05,596 --> 00:23:09,956 Speaker 2: to hear their stroke with another stroke. So this idea 386 00:23:10,196 --> 00:23:14,196 Speaker 2: is testable and we are in parallel testing it in 387 00:23:14,276 --> 00:23:17,436 Speaker 2: collaboration with the Xylor lab. This is not a social 388 00:23:17,476 --> 00:23:20,516 Speaker 2: critical period this is a motor critical period. So let's 389 00:23:20,556 --> 00:23:24,116 Speaker 2: test the idea that in this context what matters is 390 00:23:24,236 --> 00:23:27,516 Speaker 2: the motor learning or the practicing a motor task, not 391 00:23:27,716 --> 00:23:30,996 Speaker 2: the social And so we're testing that and combining with 392 00:23:31,036 --> 00:23:34,796 Speaker 2: different psychedelics, but we're comparing all of those different conditions 393 00:23:34,836 --> 00:23:37,756 Speaker 2: to test this idea in mice, and then in parallel, 394 00:23:37,756 --> 00:23:40,196 Speaker 2: we will do the study to look at you know, 395 00:23:40,316 --> 00:23:42,276 Speaker 2: trying to reopen in humans. 396 00:23:43,156 --> 00:23:45,796 Speaker 1: And so the mouse study is underway now, and you're 397 00:23:45,796 --> 00:23:48,636 Speaker 1: trying to get funding for the human study, that's right. 398 00:23:49,716 --> 00:23:51,556 Speaker 1: And then once you have the money, then you go 399 00:23:51,676 --> 00:23:54,236 Speaker 1: to the institutional review board and say can we do this? 400 00:23:55,356 --> 00:23:58,636 Speaker 2: Yeah, you know, everything's queued up and wow, you know, 401 00:23:58,716 --> 00:24:01,156 Speaker 2: everything is basically ready to go. 402 00:24:01,276 --> 00:24:02,276 Speaker 4: We just need the money. 403 00:24:03,316 --> 00:24:08,076 Speaker 1: So non trivial, but it's a lot probably surmountable. 404 00:24:08,236 --> 00:24:10,596 Speaker 4: Yeah, yeah, I mean it's a lot of money. 405 00:24:10,596 --> 00:24:13,156 Speaker 2: We're asking for a million dollars to run, you know, 406 00:24:13,236 --> 00:24:16,316 Speaker 2: a safety trial and about twenty people. And then if 407 00:24:16,356 --> 00:24:18,996 Speaker 2: that phase one trial goes well. The way the trial 408 00:24:19,076 --> 00:24:22,436 Speaker 2: is designed is that it will allow us to collect 409 00:24:22,476 --> 00:24:25,396 Speaker 2: just a little bit of in addition to how well 410 00:24:25,476 --> 00:24:28,316 Speaker 2: this patient population, right, because these are older people who 411 00:24:28,356 --> 00:24:32,116 Speaker 2: have other medical issues, so we just want to be 412 00:24:32,276 --> 00:24:34,836 Speaker 2: double sure that you know, these drugs are safe in 413 00:24:34,876 --> 00:24:38,196 Speaker 2: this population. But the way we've designed the trial is 414 00:24:38,196 --> 00:24:41,396 Speaker 2: it'll give us some hints about efficacy, so we'll test, 415 00:24:41,636 --> 00:24:43,476 Speaker 2: you know, a little bit of you know, their ability 416 00:24:43,476 --> 00:24:46,276 Speaker 2: to recover motor function. And the most important thing about 417 00:24:46,276 --> 00:24:48,516 Speaker 2: the human trial and the way that I the reason 418 00:24:48,556 --> 00:24:51,556 Speaker 2: that I paired up with Steve and John is because 419 00:24:51,636 --> 00:24:56,796 Speaker 2: they have actually developed a sort of gamified virtual reality 420 00:24:56,836 --> 00:25:01,356 Speaker 2: context for delivering this physical therapy. It's a virtual reality 421 00:25:01,676 --> 00:25:05,836 Speaker 2: kind of room, and the cameras track the person's body 422 00:25:05,836 --> 00:25:08,956 Speaker 2: position in space, and as they move their arm around, 423 00:25:09,436 --> 00:25:12,276 Speaker 2: a dolphin on a screen moves around, and it's sort 424 00:25:12,276 --> 00:25:15,636 Speaker 2: of a fun way to get people to practice moving. 425 00:25:16,036 --> 00:25:19,076 Speaker 2: But it's also a little bit more play like, which 426 00:25:19,116 --> 00:25:23,476 Speaker 2: is more the way that we learn during our childhood. 427 00:25:23,796 --> 00:25:26,236 Speaker 2: So there's this shift in the way we learn between 428 00:25:26,316 --> 00:25:31,956 Speaker 2: childhood and adulthood from exploratory learning to sort of goal 429 00:25:32,076 --> 00:25:36,676 Speaker 2: directed exploitatory learning, and so we want to kind of 430 00:25:36,716 --> 00:25:39,236 Speaker 2: mimic that as much as possible, to make it fun 431 00:25:39,716 --> 00:25:42,196 Speaker 2: and to make it not be goal directed. 432 00:25:42,356 --> 00:25:48,116 Speaker 1: They're already doing that sort of psychedelic adjacent sounding thing 433 00:25:48,596 --> 00:25:51,436 Speaker 1: where your arm is a dolphin and you're playing. They're 434 00:25:51,436 --> 00:25:53,836 Speaker 1: doing that without psychedelics, and you're like, let's definitely add 435 00:25:53,836 --> 00:25:55,636 Speaker 1: some psychedelics to that. I mean, is that not to 436 00:25:55,636 --> 00:25:59,196 Speaker 1: be glib about it, but they're already doing that without psychedelics. 437 00:25:58,756 --> 00:25:59,156 Speaker 4: That's right. 438 00:25:59,196 --> 00:26:04,516 Speaker 2: So they have developed that whole paradigm to test the 439 00:26:04,596 --> 00:26:09,796 Speaker 2: efficacy of that sort of gamified environment compare to standard 440 00:26:09,796 --> 00:26:13,236 Speaker 2: of care, because standard of care is really mostly just 441 00:26:14,316 --> 00:26:18,836 Speaker 2: teaching patients how to say the other hand, to zip 442 00:26:18,876 --> 00:26:22,196 Speaker 2: their zipper and brush their hand. It's really compensatory, not 443 00:26:22,796 --> 00:26:27,076 Speaker 2: trying to bring back the lost motor function. And so 444 00:26:27,196 --> 00:26:30,796 Speaker 2: they've done head to head studies of the virtual reality 445 00:26:31,236 --> 00:26:36,316 Speaker 2: game version versus standard of care during that open state, 446 00:26:36,356 --> 00:26:38,676 Speaker 2: of the normal open state of the critical beers, so 447 00:26:38,756 --> 00:26:43,756 Speaker 2: right after the stroke. They've shown that there's better outcomes 448 00:26:43,796 --> 00:26:47,756 Speaker 2: if they use this gamified version. And so now we're saying, okay, 449 00:26:47,876 --> 00:26:51,636 Speaker 2: let's take all those people who didn't get the optimal 450 00:26:51,716 --> 00:26:54,396 Speaker 2: therapy right after their stroke, people who had a stroke 451 00:26:54,436 --> 00:26:56,796 Speaker 2: a year ago, and go back and see if we 452 00:26:56,836 --> 00:27:00,476 Speaker 2: can reopen this critical period and then give them what 453 00:27:00,516 --> 00:27:03,236 Speaker 2: we think is the better therapy in terms of this 454 00:27:03,316 --> 00:27:04,556 Speaker 2: virtual reality. 455 00:27:08,196 --> 00:27:21,116 Speaker 1: We'll be back in a minute with the lightning round. Okay, 456 00:27:21,276 --> 00:27:22,636 Speaker 1: let's finish with the lightning round. 457 00:27:24,316 --> 00:27:24,676 Speaker 4: Okay. 458 00:27:25,716 --> 00:27:28,756 Speaker 1: What's your biggest professional disagreement with your mother. 459 00:27:30,876 --> 00:27:33,276 Speaker 4: Whether psychedelics can cure allergies? 460 00:27:34,836 --> 00:27:35,156 Speaker 1: Go on. 461 00:27:35,916 --> 00:27:41,356 Speaker 2: Okay, Well, so my mother is an allergy and immunologist clinician. 462 00:27:41,796 --> 00:27:45,276 Speaker 2: She's retired now, but you know, I've told her this 463 00:27:45,396 --> 00:27:49,796 Speaker 2: crazy idea that we had about psychedelics and she was like, no, 464 00:27:49,996 --> 00:27:52,236 Speaker 2: that's not how it works. And the idea is based 465 00:27:52,236 --> 00:27:54,356 Speaker 2: on the fact that, you know, there's some evidence to 466 00:27:54,396 --> 00:27:58,196 Speaker 2: support the notion that allergy happens because you know, the 467 00:27:58,236 --> 00:28:01,036 Speaker 2: immune system, the part of the immune system that's normally 468 00:28:01,116 --> 00:28:07,156 Speaker 2: supposed to fight off parasitic infections, is being underutilized by 469 00:28:07,196 --> 00:28:11,076 Speaker 2: our modern diets, which are put more parasite free than 470 00:28:11,196 --> 00:28:16,036 Speaker 2: our evolutionary history, and so it's sort of left jobless 471 00:28:16,076 --> 00:28:19,956 Speaker 2: and it's looking for a job. And my idea is that, well, 472 00:28:19,956 --> 00:28:22,636 Speaker 2: maybe the brain is assigning the job and saying that 473 00:28:22,756 --> 00:28:24,916 Speaker 2: dog barked at you, that's scary, that's the threat to 474 00:28:25,076 --> 00:28:29,116 Speaker 2: go after that immune system, and that if that's a 475 00:28:29,236 --> 00:28:33,636 Speaker 2: learned association that the brain decided that it could unlearn 476 00:28:33,636 --> 00:28:33,996 Speaker 2: it too. 477 00:28:34,116 --> 00:28:35,556 Speaker 3: By reopening this critical period. 478 00:28:35,676 --> 00:28:36,996 Speaker 4: It's totally speculative. 479 00:28:36,996 --> 00:28:39,556 Speaker 2: I have to say, like, I don't believe it enough 480 00:28:39,596 --> 00:28:42,836 Speaker 2: where I'm like out, you know, doing psychedelics and snuggling 481 00:28:42,916 --> 00:28:43,636 Speaker 2: up to a horse. 482 00:28:43,676 --> 00:28:46,356 Speaker 4: I would love to cure my horse allergies. But I don't. 483 00:28:46,516 --> 00:28:48,396 Speaker 4: I don't believe it enough to go for it. 484 00:28:48,436 --> 00:28:51,316 Speaker 3: I think it's a testable hypothesis that we should study. 485 00:28:51,436 --> 00:28:53,596 Speaker 1: And your and your mom believes it even less than 486 00:28:53,596 --> 00:28:53,836 Speaker 1: you do. 487 00:28:54,436 --> 00:28:54,876 Speaker 4: That's right. 488 00:28:55,676 --> 00:29:01,396 Speaker 1: Yes, what's your favorite portrayal of a psychedelics of a 489 00:29:01,436 --> 00:29:04,196 Speaker 1: psychedelic experience in you know, in whatever, in a book, 490 00:29:04,236 --> 00:29:05,276 Speaker 1: in a movie, in music. 491 00:29:07,876 --> 00:29:11,956 Speaker 2: I really still have a soft spot in my heart 492 00:29:12,036 --> 00:29:15,916 Speaker 2: for the Huxley description of him staring at a chair, 493 00:29:16,436 --> 00:29:19,516 Speaker 2: because you know, as a scientist, I have to say 494 00:29:19,876 --> 00:29:23,036 Speaker 2: that one really resonates. Like I'm not a religious person, 495 00:29:23,516 --> 00:29:26,796 Speaker 2: mystical experiences, that stuff doesn't really resonate with me. But 496 00:29:27,396 --> 00:29:31,276 Speaker 2: he's staring at a chair and sort of being mesmerized 497 00:29:31,316 --> 00:29:35,836 Speaker 2: by the you know, asymptotic distribution of chair molecules the 498 00:29:35,876 --> 00:29:38,676 Speaker 2: further away you get from the chair, and then the 499 00:29:38,756 --> 00:29:41,436 Speaker 2: Huxley molecules the further and then you know, the two 500 00:29:41,476 --> 00:29:43,476 Speaker 2: of them sitting on each other and suddenly they're inert 501 00:29:44,156 --> 00:29:47,036 Speaker 2: they're intermixed, and Huxley is the chair. 502 00:29:47,076 --> 00:29:49,396 Speaker 4: I mean that that resonates. 503 00:29:48,876 --> 00:29:52,676 Speaker 1: But have you ever taken psychedelics for work? 504 00:29:54,116 --> 00:29:54,756 Speaker 4: I don't know. 505 00:29:55,756 --> 00:29:58,836 Speaker 2: Yeah, I don't really want to talk about that or 506 00:29:58,876 --> 00:30:00,116 Speaker 2: answer that question. 507 00:30:00,316 --> 00:30:04,236 Speaker 1: Mine totally reasonable. Do you have any advice for people 508 00:30:04,276 --> 00:30:06,756 Speaker 1: who are considering taking psychedelics recreationally. 509 00:30:08,436 --> 00:30:10,756 Speaker 2: Yeah, it would say that, you know, these are powerful 510 00:30:10,796 --> 00:30:15,476 Speaker 2: medicines and that we should honor and respect their power, 511 00:30:15,716 --> 00:30:18,676 Speaker 2: and that they're doing something. If we're right, they're doing 512 00:30:18,716 --> 00:30:23,436 Speaker 2: something very big to the brain, and that this transformation 513 00:30:24,316 --> 00:30:27,196 Speaker 2: should not be taken lightly. And you know, I would 514 00:30:27,236 --> 00:30:31,436 Speaker 2: also emphasize that our studies suggest that once you reopen 515 00:30:31,476 --> 00:30:36,676 Speaker 2: these critical periods, especially with psilocybin, MDMA and LSD, they 516 00:30:36,716 --> 00:30:40,356 Speaker 2: stay open for several weeks after the acute effects of 517 00:30:40,396 --> 00:30:43,556 Speaker 2: the drug wear off, and so you're gonna be in 518 00:30:43,676 --> 00:30:47,676 Speaker 2: a in a sort of vulnerable state that's reminiscent of childhood. 519 00:30:48,156 --> 00:30:51,596 Speaker 2: And I would say be very very cautious about who 520 00:30:51,676 --> 00:30:55,716 Speaker 2: you expose yourself to during that period. You know, if 521 00:30:55,716 --> 00:30:59,156 Speaker 2: you're in a traumatic relationship, it's probably a good idea 522 00:30:59,196 --> 00:31:01,916 Speaker 2: to stay away from your traumatizer for a couple of 523 00:31:01,956 --> 00:31:05,436 Speaker 2: weeks after you've taken the drug, you know. I think 524 00:31:05,476 --> 00:31:08,756 Speaker 2: that we can learn a lot from the history of 525 00:31:08,796 --> 00:31:09,716 Speaker 2: these drugs. 526 00:31:10,196 --> 00:31:10,476 Speaker 3: You know. 527 00:31:10,876 --> 00:31:14,436 Speaker 2: Charles Manson is a good example of somebody who gave 528 00:31:14,476 --> 00:31:18,876 Speaker 2: psychedelics to people and then used it to, you know, 529 00:31:18,916 --> 00:31:21,876 Speaker 2: when they were in this vulnerable state, which presumably lasted 530 00:31:21,916 --> 00:31:25,276 Speaker 2: for a long time, to indoctrinate them into his way 531 00:31:25,316 --> 00:31:28,396 Speaker 2: of thinking, and turned a bunch of hippies into killers 532 00:31:28,396 --> 00:31:31,796 Speaker 2: who were going to, you know, induce helter skelter to 533 00:31:31,836 --> 00:31:36,076 Speaker 2: save the world. This is the sort of awesome power 534 00:31:36,116 --> 00:31:39,036 Speaker 2: of these drugs that we need to be very mindful 535 00:31:39,076 --> 00:31:42,476 Speaker 2: of and not treat them like little toys. 536 00:31:43,636 --> 00:31:45,916 Speaker 1: Anything else, anything else we should talk about. I know 537 00:31:45,916 --> 00:31:47,156 Speaker 1: you've got to go. I don't want to keep you, 538 00:31:47,156 --> 00:31:48,756 Speaker 1: but if there's anything else you want to say. 539 00:31:49,196 --> 00:31:53,116 Speaker 2: Please, I think we covered a lot, super fun. Thank 540 00:31:53,156 --> 00:31:56,956 Speaker 2: you so much, any. 541 00:31:56,276 --> 00:32:03,236 Speaker 4: Thanks one million dollars. 542 00:32:06,516 --> 00:32:09,996 Speaker 1: Gool Dolan is a professor of psychology and science at 543 00:32:10,076 --> 00:32:14,596 Speaker 1: UC Berkeley. Today's show was produced by Gabriel Hunter Cheng. 544 00:32:14,916 --> 00:32:18,276 Speaker 1: It was edited by Lyddy Jean Kott and engineered by 545 00:32:18,316 --> 00:32:21,876 Speaker 1: Sarah Bruguier. You can email us at problem at Pushkin 546 00:32:21,996 --> 00:32:25,156 Speaker 1: dot Fm. I'm Jacob Goldstein and we'll be back next 547 00:32:25,196 --> 00:32:37,396 Speaker 1: week with another episode of What's Your Problem.