Sean Carroll's Mindscape: Science, Society, Philosophy, Culture, Arts, and Ideas - 82 | Robin Carhart-Harris on Psychedelics and the Brain

Episode Date: February 3, 2020

The Convention on Psychotropic Substances was a 1971 United Nations treaty that placed strong restrictions on the use of psychedelic drugs — not only on personal use, but medical and scientific research as well. Along with restrictions placed by individual nations, it has been very difficult for scientists to study the effects of psychedelics on the brain, despite indications that they might have significant therapeutic potential. But this has gradually been changing, and researchers like Robin Carhart-Harris have begun to perform controlled experiments to see how psychedelics affect the brain, and what positive uses they might have. Robin and I talk about how psychedelics work, how they can help with conditions from addiction to depression, and how they can help people discover things about themselves. Support Mindscape on Patreon. Robin Carhart-Harris received his Ph.D. in psychopharmacology from the University of Bristol. He is currently the Director of the Centre for Psychedelic Research in the Department of Brain Sciences at Imperial College London, and holds an honorary position at the University of Oxford. His research involves functional brain imaging studies with psilocybin (magic mushrooms), LSD, MDMA (ecstasy) and DMT (ayahuasca), plus a clinical trial of psilocybin for treatment-resistant depression. Web site Centre for Psychedelic Research Google Scholar page Talk on Psychedelics: Lifting the Veil Twitter

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This is, I think, in the Enlightenment period in Europe, one of the first works to come out strongly in favor of being an atheist. There were hints by various people that maybe God wasn't all he was cracked up to be, but still this was absolutely clear, man a machine, that God didn't exist. We human beings are more like machines than embodied spirits. The 18th century was a big time for machines in France and the rest of Europe, so this is a vivid metaphor at the time. And Delometri was not one of the world's great philosophers, but he was more like a pundit, I guess we would say, in these days.

He had very vivid metaphors and language and examples. he put his case in a very clear way for people to understand. I remember one of the points that he made, I'm paraphrasing now, it's been years since I read it, but basically he was arguing against René Descartes' idea of mind-body dualism, that a human being is a body, but then there's also a mind that is disembodied, and somehow they talk to each other, and that makes the person. So Delametry didn't buy this. He basically would say that the human being is a physical object,

and the mind is emergent in our modern language. But the example he used was he says, look, when I have had my cup of coffee or not had my cup of coffee, I'm a different person, depending on whether that's happened or not. How can you possibly believe that the mind is completely separate from the body when it's perfectly clear that my mind is deeply affected by what happens to my body? It's a very good point, really, and of course the people who don't believe him have answers to it, etc. But nevertheless, the example lingers in your mind. These days, when we know even more about how the brain works, how the body works, how the mind works, but still don't know nearly enough, we're advancing in the direction of understanding not just how the mind works, but how to change how the mind works by messing with it, by giving it coffee or giving it other sorts of substances. So today I'm talking to Robin Carhart Harris, who is head of the Center for Psychedelic Research in the Division of Brain Sciences at Imperial College London. Robin is one of the first people, maybe the first people, to study the effects of LSD and other psychedelic drugs on patients in controlled clinical trials.

I should say he and his collaborators, right? It's medicine. There's a lot of people working on this. But for years now, following the dictates of the United Nations of all people, Most countries have just held all research into psychedelics off limits, and those rules are finally beginning to soften a little bit. So we can do things like give a patient some LSD or some psilocybin, put them in an MRI machine, and see what's happening to their brain. We're learning a lot. We're learning about both how the brain works for its own purposes.

We're curious about that. But we're also learning about how there might be therapeutic advantages to using drugs like this. There was a certain reputation that psychedelics got in the 60s and the 70s, and that gave them a bad image as far as public relations is concerned. But there's enormous potential here for using these for treating depression, for treating addiction, for end-of-life care, for pain management, or just for helping people sort of become at peace with themselves in different ways. It's very early days, I think, for the research here. We really don't know. That's why it's so fascinating to start thinking about it.

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Toyota, let's go places. So remember the podcast, Mindscape has a web page, preposterousuniverse.com slash mindscape, where you can get not just the show notes for this, links to people's web pages and their research publications or what have you, but also full transcripts of all the episodes. There are links you can click on if you want to donate or things like that. People who donate and become Patreon members don't get ads on their podcasts, and they also get monthly Ask Me Anything. episodes. And with that, let's go. Robin Carhart Harris, welcome to Mindscape Podcast. Thank you. Nice to be here. So there's a lot to discover here about psychedelics and therapies in the brain and

things like that. But this is a topic unlike some that I do, where I'm presuming that many of the listeners either have experience or opinions. At least they know what LSD and magic mushrooms and things like that are. But there's a history that I think is fascinating. Why don't you say a few words about the history about, you know, how these things came to be and also the legal choices that made it difficult to study them over the years. Yeah, sure. I mean, I guess the history comes in a few phases. People have talked about waves. You know, you have the first wave of psychedelic plant medicine use, which is ancient and, you know, major geographical areas in Central America and South America where psychedelic plant medicines have been used for, you know, countless generations.

Do we know a lot about how deep that goes back in the history of those things in South America? Some people do. It's not my area of particular expertise, but it goes back to with mushrooms. I think it's fair to say thousands of years in Central America. Okay. in terms of mushroom-related artifacts. I mean, they could be something else,

but they look pretty mushroom-like. And pictures as well that go back a long way that depict mushroom ingestion. Ayahuasca is difficult to know because of perhaps a lack of artifacts, but at least several hundred years back and very much ingrained in certain colors. in Peru and Brazil.

Yeah. And then... With an LSD, for example, we discovered in the 20th century, right? We did. Yeah. So Albert Hoffman, who was kind of commissioned by a drugs company, Sandos, to play around with some Ergot derivatives. That was his expertise. So Ergot is a fungus that grows on certain grasses, rye grass. and was associated with, you know, some interesting vascular effects and also some intoxication as well, poisoning.

And so he was looking at the potential vascular effects of the drugs potentially related to stemming, bleeding in birth. Okay. So he wasn't looking for mental effects? No, it wasn't. So it was a classic, you know, medical serendipity that led him to... And when was this? This is 1938. He was playing around with the drugs.

The war happened. Things got shelved and it was 43 when he now famously took, was 200 or 250 micrograms, which he thought was a tiny amount of LSD. Turns out that's a pretty big trip. And then the... now celebrated bicycle day. The first bicycle day happened then in April, I think, the 19th, 1943. He took that dose of LSD and was shocked at the effects, thought he was dying.

Actually, before he got there, he jumped on his bike and rapidly cycled home because he, you know, wanted somewhere comfortable, perhaps if he felt he was on his way out. But it describes what sounds like quite a nightmarish experience. His neighbor comes around and she turns into a malevolent witch who he thinks poisoned him. And yeah, he thinks he's dying. And yeah, so that's the second wave. And now we're in this renaissance period, the so-called third wave. So, yeah.

And in between we have the 1960s. A good time in some sense. A good time in some sense, but I guess a sad time in another sense in terms of the pushback against psychedelic drugs, which had very significant implications for psychedelic drug research and medical use leading to essentially an outright ban on any kind of work with psychedelics from the late 60s onwards. And it's been decades, really, of a hiatus in research until, I guess, in the 90s most significantly, have characters like Rick Strassman and Franz Volumvider doing pioneering work to bring psychedelic compounds back into the scientific space. And then the naughties, you know, with significant things happening at Johns Hopkins, I guess we come onto the scene in the UK in the late noughties around 2009.

I started brain imaging research with psalocybin. And we find ourselves here today where, you know, this is starting really to become quite mainstream. And it was banned internationally in the 60s, right? There was some like the United Nations put, they don't have much legal authority, but they did at least recommend that countries not let you use psychedelics for therapeutic purposes. Is that? Yeah, it was a UN-wide initiative. So any countries that fell firmly under that were implicated, and that's most Western countries.

In the Eastern Bloc, actually, they carried on for a little bit longer doing work in the Czech Republic. And a certain Stanislav Groff, who's such a key figure in psychedelic work, he carried on doing research with LSD into the early 70s, but then that dried up as well. And is it true that part of that was actually a backlash literally against hippies using LSD and protesting Vietnam and stuff like that? Yeah, there's a few conspiracy theories, but I don't think you have to be too inventive in your imagination to see how these things fit together. and it was a time of particular social and political conflict in the US, very polarised. And it seems there was a fear that perhaps psychedelics were fueling some of the countercultural sentiments.

Yeah, and probably just a few things were going on. in terms of certain politicians seeing that it can be a potent, you know, vote winner to be seen as being hard on drugs. Yeah, top on crime, yeah. Yeah, exactly. And I guess Nixon sort of embodied that with war on drugs. And before that, I don't know, with LBJ, it was him, really, who started to, you know, curtail things. and maybe it was Vietnam and a fear of people not being so loyal and obedient and perhaps having a bit of an anti-authoritarian spirit and that being tied up with the whole psychedelic and drug use thing. Okay, but now we're sitting here in your office at Imperial College in London where you do research on these substances.

Presumably it's legal. Did they change the law or did you get an exception? Yeah, it's an exception. you get a license from the home office. And it's not trivial to get one, and they're quite expensive, and that's a shame because it hampers science, hamper's collaboration.

It's not easy just to send some drug off to another team or take it over to them. And they need to be recognized and listed with a home office, and if they're setting up, they have to set aside a few thousand pounds and a bit of building work. You need a fridge that's locked, bolted to the wall, and there are inspections and such like.

And these things might seem kind of trivial, but you have to be really motivated to make them happen. And it's quite easy, you know, with all the relevant pressures that you have in any domain, but in academia, to just not bother, you know. And so... It's hard enough for me to get a grant to do theoretical cosmology, much less, you know, get a drug, you know, visiting sense to the lab must be a whole other thing.

Well, grant winning has been so difficult, I think. There's only been one or, I mean, the medical research council in the UK supported our depression work. And that's kind of an exception. NIHR in the UK have supported a colleague of mine. So that was a year ago or so. So things might be changing. but I know not much has happened in the U.S. with NIMH. And, you know, you have some obvious absentees there in terms of major funding bodies

that haven't supported this, and that's got to change soon. I want to pause for a second to talk about policygenius.com. If you're like me, buying insurance is something that you know is really necessary, but you don't look forward to it. It's a mess. of different choices out there, you're not sure which policy to buy, etc. PolicyGenius.com makes all that very easy. It makes getting the right life insurance or home insurance, auto insurance, disability insurance, all that stuff will be a breeze. One thing it does

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psychedelics? For one thing, is it fair just to use the catch-all phrase psychedelics, or do we need to really distinguish between the different ones we could take? Yeah, I think we need to distinguish. It's a very sort of broad-brushed term as this extended definition of psychedelic, which I guess in a sense exploits the word itself, the etymology there. Psychedelic means mind manifesting or mind-revealing. And so people might say, oh, when you smoke cannabis, you can have these major psychological insights. And when you take MDMA, you can have insights and some self-realization. So under, you know, that definition will extend the definition of psychedelic to include these compounds.

Another way of... But so, but, sorry, but technically most people who do psychedelic research would not include marijuana, for example? I wouldn't because, you know, I guess it's the science thing where you know, you know, know you need to be crisp in your definitions. And so for me, the best scientific definition is one that comes from the pharmacology, which is classic psychedelics. And some examples there would be LSD, arguably the prototypical psychedelic, because it was only after its discovery that the term came along. Mesklin as well, given that Humphrey Osmond came up with the word in he was a Canadian, well, he was British psychiatrist working in Canada.

He became friends with Aldous Huxley of a brave New World and The Doors of Perception, which was his essay on his mescaline experience. Okay. And the mescaline was provided by Humphrey Osmond. And so from that, there was, you know, a realisation, shared realization that we needed a new term for this category of drugs, Osmond came up with psychedelic. But, yeah, so mescaline played a role in the birth of that term as well, a key role. So LSD as a tryptamine, and triptomines are compounds that molecularly are very similar to

serotonin, five hydroxy-triptamine. and another one is dimethyl tryptamine, DMT, which is found endogenously in very small amounts in humans and many other animals, we think, and lots of plant species. DMT is the major psychedelic ingredient in ayahuasca, this Amazonian brew. So there's some examples, but the crisp definition is that all of these

classic psychedelics share a certain pharmacological property, which is that they stimulate a certain serotonin receptor, the serotonin 2A receptor. And then I could say a lot of, I think, interesting things about the 2A receptor, where it is in the brain, what it's associated with. I think you should say those interesting things. Yeah, where is it in the brain? So what is, I mean, this is a neuroreceptor in individual neurons? Yeah, yeah, it sits in the membrane of individual neurons. And the first thing to say is that the receptor is heavily expressed in the cortex, that aspect of brain that humans have so much of all the wrinkly stuff, and, you know, massively expanded in our species, and that's where you find these key receptors that psychedelics work on.

So we're going to be more susceptible to psychedelics than cats and dogs? Probably. They seem sensitive too, but they don't, you know, their behavioral repertoire. Who would know, really? You know, so they just twitch and that kind of thing. That's our behavioral index of whether dogs and rodents are tripping or not. Yeah, in humans, we have lots of cortex. We have lots of 2A. Serotonin 2A is the receptor.

And it's not entirely evenly distributed in the cortex. The cortex, like so much of the brain and so much of the body, and nature is hierarchical, has a hierarchical organization. And at the top of the hierarchy, you have the association cortex, which in a sense is the most mysterious because it doesn't have an obvious modular function like the visual system, for example, you know, which most of the visual systems in the back of the brain. Right. It's clear what that does.

Yeah. And the motor systems for movement, motor action. But the association cortex is sort of like a lot of things and associated with association and high level psychological functions like imagination. So stitching things together and coming up with scenarios. Yeah, yeah. Stitching things together, imagining things that aren't there immediately in the environment. So that's referred to as counterfactual thinking. something that people say might be unique to our species.

Another thing that people say is probably unique to our species, at least in the magnitude that we have it, is self-consciousness, probably what sets us apart. And that's where, you know, that's a function associated with the association cortex when you see so much of these two A receptors. So that's a good starting point, you know, the receptors in an aspect of the brain that evolutionarily is quite recent.

and massively, you know, expanded in our species and associated with these high-level functions. Then we could look at what happens when you stimulate that receptor to brain function. And there I've introduced a notion which I hope is useful, this entropic brain idea. Oh, okay. Where entropy... We're big fans of the word entropy here in the Minescape podcast. And this is where, in a sense, I'm stretching my expertise because it's not in physics. physics, or in information theory.

But I know that in information theory, entropy is quite a fundamental metric related to our uncertainty about a system, where if entropy is high, uncertainty's high, we don't know what that system's going to do next. It's unpredictable. And there the principle with psychedelics is quite simple, this entropic brain principle. which is that psychedelics increase the unpredictability of spontaneous brain activity. So rather than spontaneous just means ongoing, rather than evoked by like a stimulus of some sort.

Right. So that even when we're trying to be quiet and stilling our minds, there's a lot going on in our brain. Yes, that's a spontaneous brain activity. Okay. You can think of, you know, a stream of consciousness and imagination, daydreaming, that. those kind of things going on. Yeah, and...

The stuff that you try to get a control over in a mindfulness exercise or at least get knowledge of. You try and still with focus. There's a few kind of interesting paradoxes there, of course. But ordinarily, you know, that quality of consciousness is pretty rich, but under psychedelics, we've found it's richer still. and we found that there's this interesting, really quite reliable relationship between the richness of ongoing consciousness, if you want, and ongoing brain activity. Maybe before we get there, what is the role of serotonin in the cortex other than psychedelics?

It naturally appears and you know what it's there for? Well, serotonin is really complex neuromodulator, so it tunes neural function rather than at being simple excitation or inhibition thing. It's more about a complex tuning. And the complexity of serotonin is reflected in its number of sub-receptors. There are at least 14 that have been identified. And they all do quite different things. Some of them actually oppose each other's function. Another thing that you see in nature. And the 2A receptor is excitatory. and it seems to increase an irregular form of excitation. And there might be a clue as to what we see at the population level,

so groups of neurons, where we see this entropic effect, where the activity becomes harder to predict, more complex. Right. In the presence of the serotonin or in the presence of psychedelics? So, well, in terms of the basal, the functioning of the serotonin, of the serotonin 2A receptor, the suggestion is that it doesn't do that much, because if you give a blocker of the 2A receptor, it doesn't really do much to consciousness.

It might make you a little bit sedated, might make your thinking a little bit narrowed and stereotyped, but it's a subtle effect, cognitive rigidity, but it's quite subtle. So that's the low entropy, high predictability kind of phase. Yeah. Yeah. And it might be associated, I guess, by implication with a narrowing of the range of conscious content, let's say. 2A blockers in medicine, antipsychotics often have a 2A blocking component and some sleep drugs as well. 2A blockade seems to promote deep sleep.

Okay. So it's kind of the opposite of what you see with psychedelics. But then there is this rule of it doesn't, the blockers don't seem to do that much. They certainly don't, you know, it's not the dramatic impact on consciousness that you see when you stimulate that receptor. Which is what the psychedelics do. Yeah. And so part of my thinking and I think others around the 2A receptor is that maybe it becomes engaged naturally during exceptional conditions. If it's not really doing much basally, so, you know, in a kind of, ongoing background kind of way, then maybe it's there for some kind of emergency situations,

perhaps crises. And I've got a paper in development at the moment which proposes that hypothesis, and I've written other things that have sort of led up to that hypothesis, that it's a kind of crisis button in a way, you know, activating the 2A system, serotonin 2A system. And so in conditions of, as somebody else has said, existential distress crises, maybe you need to induce these very plastic brain and mind states. But the brain be more flexible. Yeah, because your life literally depends on it. Or, you know, your, I guess, well-being very much depends on it.

Like something has to give, something needs to change. You're having some kind of psychological breakdown, whatever complex reasons, you enter this state of hyperplasticity. And then beyond that, maybe life is never the same again. Okay. You can think of examples like epiphanies,

religious epiphanies, hitting rock bottom and major transformative experiences. They happen, you know, outside of the context of psychedelics. So it's natural to us, why do they happen, how do they happen, maybe they happen in a related way to how psychedelics work. Okay. And so when we take the psychedelics, and so we are grouping all the psychedelics together in this conversation. Should we be more careful about? Well, yeah. I mean, distinguishing which one does what.

Yeah, when I talk about psychedelics, I'm really talking about the classic psychedelics. And I think it's probably most useful for listeners to think of the examples. LSD, salocybin, which is found in magic mushrooms. DMT, which is found in lots of plants and in ayahuasca, mescaline as a phenethlamine, it's a slight different class, but it's still a classic psychedelic. Okay, so all these stimulate, this particular serotonin receptor. Yeah. And so I didn't quite get clear how I should think about what this is doing to the brain.

So there's a lot of things going on in our brain, even when we're trying to be quiet, or our eyes are closed or whatever. and my impression is that the psychedelics, rather than excite the brain, they sort of let the brain have some access to what's going on anyway in some sense. Is that fair? Yeah, it is fair. It is an excitation, but it's an irregular form of excitation. So perhaps rather than think of it in a quantitative way, you know, where people have historically, they talk about regions in the brain lighting up or metabolism increases. or decreasing a little bit like some like a thermostat or something you know going

hotter or colder that's a little bit of these days a bit of too crude a way to depict the brain where it might be better to think of the quality of brain activity changing okay and there the thing to say is that the regularity of brain activity changes activity becomes dysregulated that's right I do remember reading about, you know, the network effects in the brain become a little bit less predictable, I guess. Yeah. Yeah. And does that have an easy relationship to the classic things that we think of as happening when we're on an LSD trip in terms of hallucinations, visual and auditory, or even, I mean, sometimes people see things that are just not there. Many times people just see things that

are there moving in weird ways, right? Yeah. Yeah. So that notion that psychedelics are hallucinogens, A little bit misleading. With eyes open, things distort. And sure, things can sort of emerge if you're looking at something like the clouds or whatever. Or you're on DMT and then things are really wild visually. But it's more when you close your eyes that the experience becomes very rich in imagery and very, very vivid as if one is seeing with their eyes closed. A bit like dreaming. Is it a bit like dreaming or is it really the same thing as dreaming in some sense?

It's probably a hybrid. It's not quite the same thing. But I've speculated and others have and there's bits of indirect evidence to back this up that the tripping state, if you want, is a hybrid waking dream state. And so part of the mechanics and physiology of dreaming is actually happening while you're awake under a psychedelic. And this actually is probably the reason that drew me into this whole area in the first place

in the same way that Sigmund Freud famously said of dreams that there were a royal road to a knowledge of the unconscious mind. Others have said the same Stan Groff and others about psychedelics. And then you put two and two together and you think, ah, by a matter of kind of converging evidence, there's something to this unconscious mind, business.

Yeah. One of the reasons I started Minescape was because I had too many books to read. And by having the authors of these books as podcast guests, I would force myself to do it. For those of you who don't have podcasts of your own, you might want to try the Blinkist app. Blinkist is a wonderful way to get a glimpse into what a book is saying without going through the whole thing. without having to read the entire book. Basically, in 15 minutes of reading, you can get an essence for what the book is actually about.

Some of my books are on Blinkist, and also other books by previous Mindscape guests. There are books by Carlo Rovelli, Adam Rutherford, and others. So with Blinkist, you get unlimited access to read or listen to a massive library of condensed nonfiction books, all the books you want, and for one low price. Right now, for a limited time, Blinkist has a special offer just for Mindscape listeners,

Go to blinkist.com slash mindscape to try it free for seven days and save 25% off your new subscription. That's Blinkist, spelled B-L-I-N-K-I-S-D, Blinkist.com slash Minescape to start your seven-day free trial. And you'll also save 25% off, but only when you sign up at Blinkist.com slash Minescape. Probably a lot of people who are not professional neuroscientists or psychologists have a pretty overly simplistic, direct view of how the brain works. Like there's a visual feel that comes in and we have a camera in our brains and there it is, right? And we hear things and that's also going on at the same time. But my impression from my rather amateurish readings in these things, it's way more complicated and there's a lot of processing going on in the brain just to give us this image of the world that we

see around us, right? Like what we think we're seeing is highly processed compared to what our eyes and visual cortex actually picks up. Absolutely. I mean, you can say it's highly constructed in a kind of top-down way, as in there's a lot that we're experiencing that comes from the brain itself rather than from the outside world. And this is what Carl Fristin will say when you have more, hopefully in a very elegant and thoughtful and precise way. But perhaps in a way that's difficult to understand.

But no, there's this notion, Asian brain based on principles of probability that we house in our brain's internal models through which we experience the world. And so much of experience is the product, in a sense, of these models that we house, rather than some kind of receptivity of information coming in. And the action of psychedelics is a bit of a clue to that being, true in the sense that we can almost see these models that we've constructed, even the really high-level ones like our sense of self.

And that's probably the most profound realization that people have on psychedelics is, oh my goodness, you know, my sense of personality is an absolute, you know, and all the spiritual related sort of follows on things that follow on from that experience come into play. Yeah, so we should think of what is happening to our brains on psychedelics, you know, not as seeing new things, but as you seem to be implying that we're revealing things that are going on inside our brain already. Yeah, it's almost like an outside of. observer, you can look at sort of in a sense how the brain and mind work. And it's probably achieved through the fact that these internal models break down.

Recently, I've written with Carl on this topic, a review paper that we've entitled Rebus for relaxed beliefs under psychedelics. A bit of a fudge. Psychedelics is not a nest, but that's a good mess. Yeah, it sounds that way. but it's hopefully it's memorable and yeah the idea is that the what's called precision weighting or confidence

that we have in our internal models so like our confidence in who we are dissolves breaks down relaxes under psychedelics and when that happens there is this you know curious possibility to step outside of the model and then almost sort of view it or view it's

realize its absence and almost have a third person perspective on our first person it throws up lots of interesting philosophical questions like then who is the observer right but well I talked to Daniel Dennett recently on the podcast and so you know he is one of the originators of this multiple drafts version image of consciousness. There's a lot going on that are sort of suggested ways of viewing the world in your brain. And then this, I guess this associative part of your cortex knits them together to make some final draft. But yeah, so no one of them is the final story, I guess. And if you get to look at them individually, you realize how non-unitary ourselves really are.

Yeah. Yeah, how the narrative's been stitched together. Yeah. Yeah, multiple drafts, yeah. And does this, you know, a lot of people have advocated the use of psychedelics for unleashing creativity in some way. Does this speak to that? Do you agree that this is a good kind of thing to do? Yeah.

Probably the, you know, the biggest block to creativity is being too sure, being too confident. Too low entropy. Yeah. Yeah. And, you know, which is, it's a. It's a curious one. And you can think of other drugs that work perhaps even in a sort of polar opposite way to psychedelics that give confidence, you know, the stimulants, maybe a drug like cocaine. We've actually published some work that based on a scale of ego dissolution and ego inflation, these two drugs go in different directions.

It's kind of an obvious thing. Yeah, I guess, but, yeah. So it makes you. a little bit more sure of yourself? Yes, it inflates the ego. It makes you maybe less creative? Possibly. Yeah.

Yeah, I mean, you might be very productive. Right, exactly. But you might come up with a lot of stereotyped, you know, manic kind of ramblings that aren't particularly rangy and expansive. Whereas with psychedelics, you really get that expansion, whether you can get the focus. Exactly, yes. It's another matter. I mean,

is the classic example of being on psychedelics and thinking that you've had a wonderful insight and you try to write something down and the next day, it's just nonsense, right? Yeah, yeah. Then the quality control comes in. The BS detector,

the editor comes in, perhaps afterwards. But, you know, perhaps not always so fiercely. And there's a lot to be. said and people are increasingly aware of this, that's the integration process, the landing process after a big psychedelic experience is so important. And there if there isn't too much haste to try and stitch things back up, but rather just let them slowly kind of settle and crystallize in a way that's most natural without forcing any kind of, I don't know, psychoanalysis. interpretations necessarily.

And it's probably in that way of treating it as a sort of organic process that things settle most healthily. And sometimes there's a, there needs to be a principle of just sitting still with some uncertainty. Perhaps things aren't so crystal clear now. And perhaps things aren't so crystal clear. Full stop. And so, you know, that often comes up, actually, in our therapeutic work with psychedelics, where a patient might want closure on something, you know, something as literal as was I abused,

you know, and there's a responsibility, I think, on our part, not to force such a closure. And there are historic examples of where that's gone wrong in traditional psychotherapy. Right. You want an answer. Yeah. Yeah. Sometimes it's just hard to get. not there, not enough evidence to decide one way or the other. Yeah.

Yeah. So there is also this feeling that, you know, informally forgetting about scientific research, but people feel that they're getting some deep insight into themselves or into the nature of existence or something like that when they're on psychedelics. And I've always wondered how much of that is you actually have gotten an insight or you have gotten the impression that you've gotten an insight somehow. I mean, are there things that really stay with people after? word, you know, once they're no longer on the drugs that are count as profound insights about

themselves? There are, but that, I mean, you're really hitting on the million dollar question there. And again, you know, the answer isn't too black and white. Sometimes people do have profound insights that stick with them, that change their lives, that they can communicate to other people who hear them and, and, and, you know, the message lands and resonates and they say wow. And when that happens, often it feels like a deep spiritual wisdom. And so the resonance really is with things that one could read about in, say, Buddhism or spiritual texts. And there, these are insights that, of course, aren't specific to psychedelics at all.

they're just more, they're more fundamental and basic than anything to do with psychedelics. It's just, it's so happened that for some people, psychedelics have been the tool that have really led to whatever breakthroughs that people have had. And for some, you know, spiritual teachers, I guess, guru, if you want, you know, some quite well-known ones. Psychedelics have actually been, especially Western ones. Psychedelics have been, you know, the door that's opened for them that later on, you know, what they've done with that drug-induced insight is to put it into spiritual practice.

Right. And there I think the key term is practice, you know, rather than just keep, going back to the drug where after a certain period of time, maybe, you know, there's more noise to be experienced than Signal. They've thought instead there's something to do. There's some action to follow that's a healthier way of being rather than going back to, you know, the drug teacher and all the projections that can go with that.

that's, you know, there's something inherent to the drug that holds this intelligence. I think that can be quite a dangerous and problematic. Well, it's very interesting what you said about the sort of loosening versus tightening of your thought processes when you're on a psychedelic versus a stimulant. There's this longstanding informal belief that madness and creativity are somehow connected to each other, right? being creative involves looking outside the box, thinking of new things, but in some sense you can the box is also important, right? Like the ordinary rules also matter and it's all about finding a balance between them. Are psychedelics a way of sort of moving the balance in one direction or another and then going

back and forth and is that useful? Yeah, it can be useful, but equally it can be potentially problematic. I mean, it can be useful when the constraints of the box are too firm, and it's holding up progress and perhaps even leading to pathology, whether personal or on a kind of systemic level, like on a social level. People do have bad trips, right? And does that depend on the person more or the drug? Well, they do have bad trips, and sometimes they are really bad.

I mean, there is this sort of fashion, I suppose, in the psychedelic science community to say, there's no such thing as a bad trip. There's challenging experiences. You call them challenging, you know, they're things to work through and overcome. And there's a lot of truth in that. But equally, for the sake of sort of plain talking, some trips are really, really awful. So we can call them bad. They're not fundamentally bad intrinsically in and of themselves.

But unpleasant to themselves. Very unpleasant. Yeah. Hellish. And so, you know, I guess as a scientist, there's some deep fascination in those experiences. And to try and understand them, I would lean towards notions of the collective unconscious, you know, Carl Jung and archetypes, you know, around sort of demons and devils and monsters, you know, very ingrained human images and ideas that are, yeah.

So you're saying that when people have a bad trip, we can try to understand what they're going through by reference to those ideas? Absolutely. I think it's the best way to understand them. A problematic way to try and understand them would be to say that they're literally real, to invoke notions of magic, that perhaps some bad. demons are in the, just bad spirits are in the space or whatever. Right.

That kind of projecting things into some metaphysical space, I think, is part, you know, one of the kind of subtle, sometimes perhaps not so subtle pitfalls of psychedelic drug use. Well, that's, you know, sometimes I get the impression that people who are advocates for this really think that they're not just discovering something new about their brains or their brains. but about the nature of reality. And I'm very skeptical about that. I'm not quite sure that the nature of reality is being revealed here. No. Although they might have some insights about the nature of nature, possibly. But then you also have these, there's a lot of pseudoscience that comes into this space,

a lot of magical notions. And a lot of contradiction that you hear as well. People will talk about, oh, the Western approach and the scientific, analytical approach and how it's so reductionist and then they'll bring up some you know loose idea around the vagus nerve that's responsible for kundalini you know and it's just all really vague and and uh horribly reductionist as well yeah so there's there is some annoying contradictions but okay speaking of the western scientific method you know here you're doing experiments Why don't you describe an actual experiment you would do on a patient by giving them some psychedelic and looking at their brain somehow?

Yeah. Okay. I mean, we have been doing some interesting work with DMT, injecting it into people and then recording. Two volunteers, I presume. Healthy volunteers. And then recording their brain activity with EEG. You know, those caps that record the oscillatory activity in the brain. They've got a little bit like swimming caps with the senses on.

And then fMRI as well. And recently we've completed a simultaneous EEG FMRI study. Okay. One of my PhD students, Chris Timmerman, has been leading that work. And so that's quite pioneering, and it allows us to bring together the high temporal resolution of EEG with the high spatial resolution of fMRI, look at things like complex patterns in the temporal activity, look actually literally at its complexity, at its entropy, but also look at brain networks and their dynamics. And there's some principles are emerging out of that. And then it's really as good science,

perhaps, or just science does, it throws up interesting new questions and future studies to think about. So with some way through, in fact, the plan is to begin this in the next month in February to begin a protocol of, well, actually begin the experiments themselves. following a continuous infusion protocol with DMT. So typically we give a bolus of DMT and it rockets people into this DMT space where they feel so profoundly immersed in this other world that feels as real as this one, but is, you know, alive.

Zero to 60 very, very quickly. Yeah, yeah. And is content rich, visually, incredibly rich. you know, that kind of avatar type scene is probably inspired. Floating cities, yeah. Yeah, from ayahuasca and DMT visions. But it's that kind of thing. And people often report encountering entities seemingly sentient other beings in this DMT world.

Which is not what you would see from LSD. No, not really. No, it doesn't quite reach that intensity. LSD, I think you mentioned. is more like the things that you do see are altered, rather instead of seeing new things. And there can be sort of perhaps richer kind of deeper notions and memories, personal material and trans-person material, can emerge under LSD over a longer time frame. And so therapeutically, those longer-lasting psychedelics, like LSD and psilocybin, oral psilocybin, Yeah, they're different in that sense.

There's more therapeutic gain to be had. Whereas DMT, IV or smoke DMT, is more like this short, sharp blast into this other very weird, hyper-real space. So how short is short? What is a typical trip last? Oh, less than 20 minutes. Less than 20 minutes. Okay. But you're meeting other sentient beings.

Yes. And people come back and their whole, you know. Which you and I like to think are made up in people. people's brains, not actual. They're not angels coming down. No, it's what an exciting opportunity for studying the archetypes, I think. And, you know, the dynamic fabric, I suppose, of the unconscious mind. That was what lured me into this space.

It was that very thing, really, when I first got into this area. And, yeah, so that's obviously a huge challenge, but that's the opportunity. So just so, I mean, some people are not going to be experts here. These are not thought to be addictive drugs that you're giving people, right? So when you get volunteers, we're pretty sure that they're safe doing these kinds of experience. Yeah, so we can go through some of the obvious things. Toxicity profile seems to be very good, especially with a compound like psilocybin, magic mushrooms. Massive therapeutic index, which is the dose that you would typically take,

or you might take therapeutically, relative to a dose that's going to cause you harm or kill you. massive window there. Right. You know. So it's not like a little bit extra is going to really close you are. No, whereas there are many medicines where it's a much tied to therapeutic, uh, licensed medicines, much tighter therapeutic index and legal drugs like alcohol, you know, very small therapy.

Well, there's no therapy. Maybe a little bit. Um, yeah. And then we can look at, um, uh, yeah, mortality risk. They don't, you know, there's, there's no risk to your physiology where this, this drug's going to kill you. At least with a compound like psinozybin. Then we can look at addiction potential, negligible addiction potential.

Animals don't self-administer psychedelics. They seem, if anything, to be fundamentally aversive. And humans only really go there, well, they can make mistakes and try and take them for recreation for fun. But then they get a rude awakening and they realize that it's true, these aren't party drives. and they shouldn't have taken LSD at the party. Yeah.

Yeah, so they're more drugs of sort of self-exploration when taken in the right way. And then people, you know, often do those explorations quite sparingly. They might do it a couple of times a year if they consider themselves a psychedelic user. When Toyota builds an electric vehicle, we don't start with a blank slight. We start with everything we know. The BZ brings Toyota's proven engineering to electric. With impressive range, intuitive technology, and Toyota reliability, BZ reflects decades of experience, reimagined for what's next.

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I think that's it. Okay. Yeah. What kind of behavioral danger? Well, if you're, you know, if you're on a high dose of LSD or psalocybin and confused and things are distorted and all this powerful emotional material is coming up, you probably shouldn't be wondering around in an urban center where there's traffic and such like. or maybe in a position of responsibility for other people.

Yeah, with your children or something. Yeah. Yeah. So there are some risks there. And there's also the psychological vulnerability which should be considered a risk. And for that reason, it's so strongly emphasized and it's so important that it is that the psychedelic be taken in the right kind of context. And that involves not just the context for the immediate experience, but also ahead of time. that you come into the experience with some intention and preparation and forethought,

and also some planning for the aftercare as well, the landing. And so if those things are covered, then all of a sudden one could make quite a rational case for, I think, opening up access to safe use of psychedelics within, certain centres, for example. When you bring patients in, do you give them some sort of psychological test to make sure they're in a good place to do this kind of experiment? Yeah, we do. I mean, we do careful screening.

Of course, if they're patients, they're often not in a good place. I shouldn't say patients, but volunteers for the experiments. Yeah. Yeah. If they are in a period of psychological distress, then if it's a healthy volunteer study, they would be excluded because it starts to blur the... Closality, I suppose. Yeah, and the lines between what's a healthy volunteer study and a patient study.

Sure, one could question that distinction anyway. But if your question is how does a certain psychedelic work in the brain, you probably don't want to blur that with some kind of therapeutic study. Yeah, okay. Yeah. And you mentioned Aldous Huxley before. He famously took, was it LSD as he was dying. He was dying of cancer.

It was very, very painful. He asked to be administered LSD, and apparently it made his passing much gentler and more pleasant. Is that one of the future therapeutic uses, end of life care that we might imagine? Yeah, it is. Yeah. And so NYU and Johns Hopkins have done some really important work there. Charlie Grove at UCLA and Peter Gasser in Switzerland.

So there's quite a few studies, and probably most of the. recent clinical trials and actually the best designed clinical trials have been these studies in end-of-life distress with double-blind randomized control trials, you know, the gold standard for clinical trials in terms of scientific rigor, those designs. And yeah, the results have been very compelling, so rapid and enduring improvements in the main mental health outcomes. which have been depressive and anxiety symptoms. So very quick and lasting reductions in those. And so put more of a human spin on it,

you know, people report feeling much more at ease with the inevitable, their inevitable passing. And they view death, their death, perhaps even death more generally as something. not to be so frightened of. I presume there are some, there's a sort of moralistic attitude in some people that that would be bad,

that you should be resisting death no matter what, and therefore you should face it as naturally as possible. But I'm very much in the camp that it is something that you should try to come to terms with, right? Yeah, well, it's inevitable. And perhaps there's some, yeah, there's some grace to dying well and some humility but sure

you know rage rage against the diamonds like that kind of thing but I mean who's saying that often is it the loved one who doesn't want you to pass but maybe there's true compassion in saying I want you to pass peacefully and

yeah very very human work in that space and and universally relevant as well. Well, you mentioned this idea of taking psychedelics in a controlled environment, you know, a few times a year or whatever. I mean, what do you foresee as the long-term good balance about how this stuff is used? So you don't, you shouldn't take LSD before you go to a party.

That seems to be something that you're saying. But what do you think is the correct, you know, social role for these kinds of things? things. Yeah. If you were the boss of the world and could set all the rules. Well, there are some red flags. Yeah, don't take them at a party. Be mindful about the dosage that you take. Don't take them for escape. That's a really important one. I think it is an important one. I mean, that's worth emphasizing. It's still you, right? Yeah. You're still facing yourself. You are and everything underneath, you know, the sort of ego self. Right. Maybe you're facing yourself. You're facing yourself. more clearly. Yeah, yeah, and that can be really where the terror comes. Eye-opening, yes.

Yeah. And so for me, I think the rollout would be these centers where there is regulation. I wouldn't advocate for, so the decriminalization initiatives that are going on at the moment are interesting and you can make the argument that people shouldn't be, you know, punished or even incarcerated for exploring their own consciousness and such like and perhaps even doing therapeutic work that could turn their lives around in a healthy way, perhaps make them better citizens. So sure, you could argue that, but is decriminalisation really the right way for this to roll out? I think initiatives that are thinking more carefully about the rollout of psychedelic,

therapy, whether that be the plant medicines themselves or the product following the classic regulatory route. Obviously, in my view, they're, you know, much more thoughtful and a much healthier way that this can roll out. And there the vision, the shared vision is of centres that are carefully managed, professionally managed, where you have key ingredients. like careful screening of people coming in for vulnerabilities to identify those red flags. You know, if someone's on the cusp of a psychotic break, perhaps they shouldn't be taking

a big dose of psalocybin, which could tip the balance in a negative way. And, yeah, to have mental health professionals there and to take care of the preparation and the supervision during the experience that people are in a very safe container with ingredients, environmental ingredients, in that space that we think are important, like music and carefully crafted music, and then the aftercare as well.

And if those things are in place, it's actually my view, and I don't mind saying this these days, that the access to that model could be very broad, not just people who have, you know, fit into whatever diagnostic category, but maybe, you know, people who are well as well that could benefit from still the effect on their psychological well-being, how it might help keep them well and have other, you know, subtle advantages in terms of, yeah, living well, and, feeling connected to other people. I think, I mean, it's an interesting angle to go down to imagine that intelligent use of psychedelics could just be part of living mentally well, like keeping up your own mental health. Is that something that makes sense?

Yes, it does. It does. And there's a huge case to be made there where the burden of mental illness is so massive that you can make a case around prophylaxis or preventative measures that, can improve things like resilience, the ability to have some flex when times get really tough, help put things in perspective. And again, these are hopefully effects

that are not just while you're on the trip, but can link on afterwards. No, these are about, yeah, afterwards really. And there, again, you know, tying the psychedelic experience in with other things that are healthy, like, you know, healthy living, healthy diet, cultivating a healthy attitude, healthy literature in a sense, and practices, maybe things like meditation, yoga.

That's where the rollout could work best, I think. It does sound like something that would be hard to establish scientifically. How much do we know, even if you can do an FMRI study to see which parts of the brain are lighting up, How much do we know about the long-term mental health benefits of having these experiences? Well, we can look at other studies. We can look at population studies. We can do cohort studies where we track people over an extended period. And we've started doing those.

So we've set up what I believe will be an incredibly valuable resource. It's already valuable, but I think the future is going to be really exciting for it. It's called Psychedelic Survey. com and through that we try and collect naturalistic data in a prospective way so that means that we collect data before the psychedelic trip and afterwards as well rather than just doing the classic survey thing which is to collect everything in retrospect and there you can't make any inferences about causality and such like this is about tracking people and ideally tracking big numbers so we can get big data. And then, you know, the great merits of big data is that you can see trends that are

otherwise quite difficult to see. You know, it's very much a popular topic in medicine and science more generally at the moment, big data. So, yeah, and there, you know, we're picking up some obvious red flags at the moment and different variables that predict responses. But that's the kind of thing that's needed, you know, that high throughput if we're going to be able to best mitigate risks and learn how to optimize delivery of psychedelic experiences. And what are the, if it's one thing that it's ordinary healthy people, we all have neuroses, we all have things we can be better at. So maybe this is part of our mental health care regime or regimen. What are the more obvious mental health problems that people have for which psychedelics might be the part of the cure? Well, again, you know, this is a space where psychedelics, where the buzz that's surrounding psychedelics now is warranted, I feel, because, you know, for so long, people, you know, probably motivated by the drugs industry have been looking for,

magic bullets that can come in and target specific diagnoses with specific chemical actions. And then you'll be cured. Yeah. And the reality is it that hasn't worked. It's not like that. No, it's not like that. And so with psychedelic therapy, sure, it's early phase data. These are just small pilot studies, really.

But that's improving. And soon there's going to be some really compelling data out there. but part of the picture is that there's a lot of different indications, a lot of different disorders that psychedelics are showing signal for depression, treatment resistant depression, anxiety, end of life, distress, addictions and different varieties, drinking, alcohol, tobacco, now eating disorders. So we're starting a trial this year. Hopkins have already started.

We think chronic pain. Others think chronic pain too. The psychological aspects of pain we think could be quite effectively treated with psychedelic therapy. Obsessive compulsive disorder. There's some preliminary data on that. And so, you know, short of wanting to sound like I'm selling a panacea, it's necessary to try and explain. why this might be the case that psychedelic therapy has what we call a trans-diagnostic action. Right. It's not a single thing for which is good.

Yeah, not a single indication that it works for. There seems to be a lot. I did want to, I forgot to emphasize this possibility of treating addiction because, of course, I think in the popular imagination drugs are addicting, but in fact, psychedelics seem to be useful in curing people from being addicted to other drugs. Is that right? That's right. Yeah, so an interesting paradox. There's quite a few things that should really challenge people's group. And maybe this is part of the jumping out of a rut cognitively.

Yes, this is it. And this brings us to the explanation of why psychotelic therapy could be trans-diagnostic in action in that a lot of these disorders involve ruts, you know, whether they're behavioral ruts. Depression especially. Yeah. Behavioral ruts addiction is very true in that. sense in that there's like a gravitational pull to the object of relief, you know, whatever it is. And the withdrawal and all the uncertainty and turmoil when it's not there, you know.

And then with depression, Matt Johnson said, you know, psychedelic therapy could be useful for addiction broadly defined. And I quite like that. Because in a sense, in addiction, in depression, the addiction if you want is the pessimism becomes so practice so habitual so heavily weighted the gravitational pull is so strong that it's like a literal depression you know it pulls you in

into that rut and then it's hard to get out and if you're out you're vulnerable to falling back in again you know and so with psychedelic therapy the therapeutic mechanisms we think is that it's almost if the landscape, if you have a literal depression, like a hole, that starts to flatten.

Yeah, the rut flattens. And now the landscapes flatter. You can explore, you can move more freely. You can see more, you know, because the arts lifted up. You can see outside of the hull. And all the possibilities there. Sometimes increasing entropy is useful, yeah.

Absolutely, yeah. Controlled increase in entropy. I mean, that's the lesson that I'm learning from all of this is that, you know, a well-functioning brain or mind is kind of all about the balance, right, between a little bit of organization, a little bit of freedom, a little bit of randomness. And sometimes that balance gets out of whack and maybe psychedelics can push us in one direction when that's appropriate. Yeah.

And it's probably a universal principle that goes beyond, mental health and the brain of, you know, destruction, breeding new organization that in some way is better in inverted commas. So what is, so just to wrap things up, I mean, what is the scientific frontier? What is it what you want to see being done at labs like yours? If, you know, if you're a pioneer here, what do you want to see being done around the world? What do we need to understand about the relationship between psychedelics and the brain for example. Yeah, there's a couple of things to say. I think a demystification process where there is this pitfall around magical thinking and pseudoscience coming into this space. I think it'd be so

healthy. Actually, it'll sound paradoxical, but on a spiritual level to understand what's going on in this aspect of nature, the human brain, when people have these very profound spiritual experiences under psychedelics and that will, you know, be hugely pioneering and progressive for understanding the brain and the mind and spiritual experiences and I think that will have a lot of healthy implications. There will be some resistance to it. I think that's a shame, but I don't, I'm confident that the naturalistic approach will win out. I mean, it has historically.

And so there will be this healthy demystification, which is good, paradoxically, for spiritual practice, I would say. So I hope that plays out. And another thing is that I hope that the mainstream doesn't push back too hard, but embraces this. but there's a lot of areas in which psychedelic therapy and psychedelic science

pushes against convention so many you know whether it's depth psychology or well that's you know hasn't been a dominant force in psychology and neuroscience for a long time so that's challenging and then drugs you know they're not everyone's cup of tea so we have to work around the fact that these are drug-assisted psychotherapies and we put aside our biases, whether they're towards biomedical models or psychotherapy models, and try and talk to each other and get on with this hybrid biopsychosocial model. And what else do we have? Well, there's so much.

Mental health itself, you know, in the stigma there. And then I think there's a lot of conventions in mainstream science and psychiatry. in medicine that could be challenged with psychedelic therapy, like the way that you do a traditional clinical trial where you pick out a specific indication, you constrain everything around these inclusion and exclusion criteria, and then because usually of financial reasons, you run a very small trial that throws up, you know, limited data set in terms of its richness. Whereas if you could set up a trial that perhaps looks at a range of different indications or a very broad population. Let's say, you know, healthies all the way up to depressed with all the neuroticism in between.

And, yeah, it's the same intervention, but maybe you can allow some adaptability in the parameters, maybe the dose, the dosage and the dosing sessions, and maybe also the integration. care and the therapeutic models could be tweaked and played with. So that's consistent with what's called an adaptive trial. And also the idea of a broad population is consistent with what's called a basket or basket trial where you're putting a lot of different things in the same basket with the same intervention. So that kind of thing's done in oncology where you would have a number of different cancers

with the same intervention. why not psychiatry? You know, one of the reasons why not probably is it slightly flies in the face or it seems to of this fashion around precision medicine. Okay. People will say, where's the precision there? But I think there's a lot to be said for the exploration and the benefits that can come from that liberal explorative approach to the science at this stage, particularly as it's quite young science.

It's somehow like 50 years of missed opportunity because, you know, it's been difficult to do this research. Yeah. Yeah, it is. And so there's a huge amount to be done. And I think, you know, the progress will benefit if we don't constrain things too heavily. But it sounds like you're optimistic that things are changing and we're going to start using this stuff more intelligent. Yeah, very optimistic. Of course, you know, you can be jackknifed when you're looking in one direction. with optimism and then, you know, something comes along and really pushes back. And that's yet to happen and we haven't seen what it's going to look like. It probably will happen. But I mean, what gives me confidence is the conviction in the model and the value of the tool. All right, Robin Carrard Harris. Thanks so much for being on the podcast. Thank you.

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