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Nearly every culture throughout history has used chemicals that alter consciousness for spiritual exploration. In the 20th century these drugs caught the attention of scientists. Psychedelics, as they were named, proved effective at treating intractable illnesses like depression and addiction. And they became a tool for studying the mind, opening “the doors of perception,” as Aldous Huxley wrote. But those doors slammed shut when President Nixon declared psychedelics dangerous and medically useless. Join scientists and “psychonauts” who are now picking up where research left off 50 years ago, experimenting with LSD, psilocybin, DMT and other psychedelics to heal—and reveal—the mind.

This program is part of the Big Ideas Series, made possible with support from the John Templeton Foundation.

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EMILY SENAY: Welcome everyone, I’m Emily Senay, tonight’s moderator. You just saw these quotes from these noted actors, musicians, authors and scientists, and they all credit psychedelics with providing them profound insights, really life changing insights. And as Oliver Sacks said, he once wrote, that psychedelics revealed to him what the mind was capable of. And in fact that’s the definition of psychedelics, the modern definition, meaning mind and soul revealing. Well these chemicals have actually been part of the human story for much longer than recent times, way before scientists elucidated their chemical structures or even named them. So tonight, before we meet our panelists and get into the discussion, let’s get a little introduction to this long, strange trip.

MICHAEL POLLAN: Humans have been using plants and fungus to change the experience of consciousness for a very long time.

NARRATOR: 9,000 year old cave paintings depict rituals with psychedelic mushrooms.

MICHAEL POLLAN: Psychedelics are often used in religious ceremonies as sacraments for divination and healing.

NARRATOR: It wasn’t until the mid 20th century that science got with the program. Early psychedelics research transformed neuroscience. We began treating five patients for 26 days. In clinical trials, psychedelics like LSD showed extraordinary potential. It’s an important drug in treatment of mental and emotional disorder. These substances rose from obscurity to miraculous promise in a matter of years. Dangerous and deadly, disastrous consequences.

MICHAEL POLLAN: All of a sudden there are these scare stories in the media.

NARRATOR: Bizarre, fatal accident, permanent brain damage.

MICHAEL POLLAN: Hyped by the government. There’s propaganda.

NARRATOR: Suicide, chromosomal abnormality. Psychedelics were soon perceived as a threat to public safety and global stability. It’s very dangerous, a very dangerous drug. President Nixon went to the narcotics bureau today to sign a drug bill.

MICHAEL POLLAN: And by the early seventies essentially the research has stopped.

NARRATOR: The golden age of psychedelic science was over. But this story began in 1943.

MICHAEL POLLAN: A young Swiss chemist name Albert Hoffman is working at a pharmaceutical company in Switzerland.

NARRATOR: Tasked with formulating a new stimulant. Hoffman quite inadvertently opened Pandora’s box.

MICHAEL POLLAN: He accidentally ingests what they called LSD 25, got it on his finger, maybe in his eye and started feeling strange and he realized there’s something psychoactive in this one.

NARRATOR: Three days later, he ingests some intentionally.

MICHAEL POLLAN: And realizes like, Oh shit, I’m losing it. Hoffman was having the first acid trip in the world. So he and his lab assistant take one of the most famous bicycle rides in history to his house where he is separating from his body, he’s seeing himself from the ceiling. Then he stepped out in his garden and everything looked jeweled with dew as if it were the first day of creation. And that is how LSD was discovered, commemorated on the April 19th as bicycle day.

NARRATOR: Sandoz, the company Hoffman worked for, provided LSD 25 for free to scientists around the world.

MICHAEL POLLAN: They basically unleashed this open source research effort where they offered huge amounts of it to any researcher basically with a nice piece of stationary. It was LSD that catalyzed our understanding of neurotransmitters and receptors and also the development of other psychiatric drugs.

NARRATOR: Clinical researchers investigated LSD as a treatment for a wide range of mental illnesses.

MICHAEL POLLAN: They looked at obsession, anxiety, depression. They looked especially at alcoholism and had a 50% success rate, which is quite remarkable.

NARRATOR: Psychedelics became a standard tool in psychotherapy.

MICHAEL POLLAN: It would help people speed the process of bringing their subconscious to where you could discuss it where the therapist. There was a lot of this going on in the fifties.

NARRATOR: There was a dark side to the research as well, both the military and the CIA saw great potential. The squad are drugged with LSD.

MICHAEL POLLAN: The CIA got very interested. First they thought LSD might be a mind control agent or a truth serum. Then they thought, well let’s weaponize it. Let’s put it in the water supply. Let’s secretly give it to foreign leaders to make them do and say stupid things. So it was one crazy idea after another. Awful, awful stuff.

NARRATOR: But it’s what was happening here at home that doomed this research.

MICHAEL POLLAN: The drugs escaped the laboratory, and then Timothy Leary gives them a big push.

NARRATOR: Harvard psychologist, Timothy Leary, developed a dubious curriculum of mind expansion and personal truth through psychedelics.

MICHAEL POLLAN: A scandal erupts. He’s fired from Harvard and then decides to become the LSD evangelist. Turn on, tune in and drop out. He’s essentially saying everybody should use this drug. And the drug is taken up by the counter culture. Richard Nixon was convinced that he was dealing with a threat from psychedelics. He called Timothy Leary the most dangerous man in America.

NARRATOR: The kids who take LSD aren’t going to fight your wars, they’re not going to join your corporations. And here Timothy Leary and Richard Nixon were in agreement.

MICHAEL POLLAN: So Nixon passed the controlled Substances Act in 1970 and that listed psilocybin and LSD as no accepted medical use and a high potential for abuse, neither of which are true. And that’s a remarkable event in the history of science. I don’t know that you can point to another time or episode where you had a very promising line of inquiry that is simply stopped for reasons that have nothing to do with the science. And we lost 30 years of research. Imagine what we would know now had we been studying these compounds for those 30 years. What we might’ve learned about depression, anxiety and addiction, consciousness and how the mind works.

EMILY SENAY: Let’s meet our panelists.

EMILY SENAY: Our first participant is a psychiatrist working to find better treatments for some of the most debilitating illnesses affecting human beings including depression, anxiety, and addiction. Please welcome Stephen Ross

EMILY SENAY: Our next participant studies the brain and the mind. Professor of cognitive and computational neuroscience at the University of Sussex in England. He has published more than a hundred papers on the nature of consciousness and the self. Please welcome Anil Seth.

EMILY SENAY: Our next participant wants to understand how babies think and what that reveals about all of us. Professor of psychology and philosophy at the University of California at Berkeley and author of the bestselling book, the philosophical baby, please welcome Alison Gopnik.

EMILY SENAY: Finally, please welcome a researcher whose ethnographic field work has brought him many times to the Amazon Rainforest. Associate professor of anthropology at McGill University in Montreal, Eduardo Kohn. So welcome everyone, and I think we need to start with understanding what we’re talking about here. And Stephen, I’m going to task you with this to define if you can, what are psychedelics? We know they’re not marijuana. We know they’re not opioids. What are they? How do we define these drugs?

STEPHEN ROSS: Well, they’re a group of drugs that profoundly alters consciousness. They do it all by activating the subtype of Serotonin receptor, the 2A receptor. All of them do that. If you block that receptor, they don’t have any psychoactive effects. And they’re unusual compared to the other drugs of abuse in that they don’t meet the definition of an addictive drug. And they’re not addictive. In fact, if anything, they have a potent anti-addictive, uh, potential.

EMILY SENAY: And what are the names of some of these drugs? Would we know them as LSD, psilocybin? Is there a list that qualifies as a psychedelic?

STEPHEN ROSS: Well, the serotonergic hallucinogens or psychedelics, there’s two different sub categories. There’s the Indolealkylamines, these are drugs like LSD, psilocybin, and DMT. DMT is found in ayahuasca, and they look remarkably similar to the endogenous neurotransmitter Serotonin. And then there’s the phenylethylamines and the prototypical here is Mescalin and these are more amphetaminergic psychedelics and their ring structure very closely resembles norepinephrine.

EMILY SENAY: So, so they work on those receptors in the brain, is that correct?

STEPHEN ROSS: All of them have a commonality of activating the 2A receptor and that what’s lead, that causes their unusual psychological properties.

EMILY SENAY: Okay. We hear a lot about other drugs like MDMA, which is also known as ecstasy and also ketamine. Where do these fall into the psychedelic classifications.

STEPHEN ROSS: Ketamine is probably the closest phenomenologically to psilocybin but it has a much different mechanism, it blocks a type of glutamatergic receptor, the NMDA receptor, and it profoundly alters consciousness too, but it’s also a dissociative anesthetic. But there are commonalities in terms of the experience and the brain function of ketamine versus psilocybin. Ketamine is actually the first psychedelic that’s available as a medicine for a treatment resistant depression. Uh, it recently was, was approved Janssen pharmaceuticals. MDMA is psychedelic-like, but it’s a very complex drug. It’s being used to treat PTSD. There’s, it has breakthrough status with the FDA and probably will be made available as a medicine in the coming years for complex PTSD and it has a host of effects. It affects the serotonergic system. It causes increase in signaling Serotonin and dopamine. It actually has some addictive properties. It also releases oxytocin and causes this sort of bonding feeling and it also deactivates the amygdala, so it puts people in a kind of altered state where they feel bonded and a sense of trust. And in the MDMA PTSD research they’re able to then go back and talk about the trauma and maybe sort of like rewrite it neutrally.

EMILY SENAY: So if we could very, in a very pithy way, define the difference between what makes a psychedelic and some other drugs like marijuana or or opioids. Is there a central feature of the experience that defines psychedelic? Anybody can jump in on this. Is there, how would you characterize the experience that makes that unique? That says that’s a psychedelic,

STEPHEN ROSS: well, the, the terminology is not great. Psychedeila, psychedelic means mind manifesting. It’s unclear what that means, but the commonality is that they all essentially dissolve the sense of the ego and they can create a sense of oneness. They’re consciousness expanding drugs and they, they do it quite potently.

EMILY SENAY: Anil you, you say these drugs do something that no other drugs do. Can we talk about what that is and this is actually the neuroscience of how they function.

ANIL SETH: Yeah, there is a difference. And I think that the big interest is we, we know quite a lot as Stephen has said about the pharmacology of the psychedelics, but the effect on the phenomenology and how we experience the world and the self is really what’s striking, what’s distinctive. And if, again, if you compare it to other classes of drugs, you have things like marijuana, which gives you this comforting haze. You have cocaine, which gives you a laser focus. You might have the morphine, which gives you a rush of pleasure and psychedelics don’t do any of these things. They work more on your perception. And people often talk about an initial sense of discomfort as sort of patterns, normal patterns of perception of the world and the self are broken down and then there’s this, the phenomenological effect seems to be that you really perceive things in a very different way, whether it’s features of the of the external world, you can see patterns and things that that weren’t previously there.

ANIL SETH: You experience yourself in a very different way too and as Stephen said, there’s a breakdown in the categories that often separate the different ways in which we normally perceive things. So we might experience ourself as not the unified separate entity that we do, or at least we think that we do day to day. I mean another question here is that we think we perceive the world and the self in particular ways and maybe we don’t actually do this all the time and that’s the mind manifesting aspect of psychedelics. It can make clear that the repertoire of the ways in which we can have conscious experiences is very much larger than we might typically be aware of, which, which as a, as a researcher whose primary interest is in consciousness itself is why they’re so fascinating.

EMILY SENAY: And, and what is happening in the brain there, there, there is an effect on the brain that increases randomness or, or there’s an effect that you can actually define, is that fair?

ANIL SETH: Well there’s many effects. I mean, this is, I think is why there’s so much work to be done. It’s a very exciting area to be in because we have this big, big explanatory gap, if you’d like. We know that these pretty much all the psychedelics work pharmacologically on the Serotonin 2A receptor. We know where that receptor is distributed. We know there are high concentrations in particular parts of the brain in the visual cortex, in parts of the brain that associate different perceptual modalities. Also in the gut, interestingly. Um, and so we know that and we know the phenomenological effects of these things. Connecting the two, so what are the effects of these targeted pharmaceuticals compounds at the level of, of the brain dynamics and brain organization. That’s what, that’s what’s interesting. And this, uh, this is one example. This is some work that we did in collaboration with a research group at Imperial College London, one of the first groups along with students to study the, these compounds in brain imaging.

ANIL SETH: And what we found in this particular experiment was that the brain on, on psychedelics, this is LSD and psilocybin, uh, becomes more random. That’s to say different, each part of the brain, what you see in this picture is different parts of the brain, the, the redder they are the more random the activity is compared to a baseline of no psychedelic. And this is just one way of saying that on psychedelics, the brain seems to be exploring a larger repertoire of possible states and that may underlie this kind of expanded space of possible experiences that we have.

EMILY SENAY: Amazing. Alison, you look at this from a very different perspective. You understand how a child’s mind works. What he just said relates to some of the things we’ve talked about earlier on before the show in, in how the child’s mind works.

ALISON GOPNIK: Yeah. So one of the things that we know from looking at children and looking at brain development is that we see in the course of development a shift from a brain that looks more like the brain that Anil is talking about. A brain that has more local connections and fewer long distance connections, um, to a brain that an adult brain that’s much more structured and also much less flexible, much less plastic. So if you’re thinking about children, what you see is that you see an early period where the brain and the mind are very good at learning. Very good at exploring possibilities, good at doing things like crazy, pretend play, not very good at putting on your jacket and getting to preschool in the morning and not very good at actually going out and acting effectively. And what cognitive scientists have been thinking about this is that there may be a real purpose for this. It’s not just that the children are sort of defective adults.

ALISON GOPNIK: If you look in areas like, yeah, if you look in areas like artificial intelligence, it turns out that there’s this basic tension between what people sometimes call exploration and exploitation. There’s a basic tension between trying to have any kind of system that’s good at exploring possibility, that’s good at creating new possibilities, new alternatives and one that’s good at focusing and getting things done and acting in the world. And what evolution seems to do is to solve this tension by giving us this long period in our human childhood, it’s longer than any other, where we can just be in this state of very wide ranging exploration. We can be noisy, we can be random, we can do strange things, we can have imaginary companions that seem, that seem vivid and real to us, um, but we don’t have to do very much. And then we can use that kind of exploration as adults to find new possibilities.

ALISON GOPNIK: And one of the challenges of human adulthood is that we seem to have some ways of going back and forth between this adult state of being very efficient but not so flexible and this more childlike state of being very creative and open, um, but not as efficient and psychedelic substances seem to reinduce something like that childhood state. And there’s actually some recent experiments suggesting that at least some of these literally open up windows of what neuroscientists call plasticity, this kind of openness, uh, openness to experience even in adults where normally that kind of openness would be shut down.

EMILY SENAY: Eduardo, you’ve, you’ve spent a lot of time in the Amazon and you say that they’ve somehow managed to achieve a balance between the two tensions that Alison is talking about, flexibility versus openness. Tell us about your experience and what you learned from them.

EDUARDO KOHN: I want to come back to the term psychedelic, which I think in traditional context is quite a, quite inappropriate term. Can think of the term, the etymology, psyche, mind or spirit and deloan, manifesting, revealing, um, Amazonians, um, use a series of technologies, one of which is a psychedelic plant, a decoction ayahuasca, uh, but other ones as well, such as dreaming to, um, to find a way to be in touch with what they consider, uh, the mind of the forest. Uh, uh, the mind-like qualities that one finds in complex living ecosystems, um, and they use that as a form of guidance and they do so in such a way that what they do is they, they kind of break down the sort of normal everyday way of living, uh, uh, adult way of living. You could say, uh, they break down the way in which we kind of get our marching orders from the languages we speak. We have our identity based on the, the way that words hold who we are and they find a way to, to communicate and be in touch with a larger communicative field. Um, part of this is quite practical, like listening to bird calls and walking in the forest and quite, and some of it’s a bit more esoteric, like remembering the interpreting dreams and taking certain psychoactive psychedelic substances.

EMILY SENAY: But they do have, there’s a ritualistic aspect to it. Is that right? And, and, and they don’t, it’s not a, um, it’s, it’s a well thought out program that they have that’s different than what we’re familiar with here. And they do it through a ceremony

EDUARDO KOHN: that’s right there. There are ceremonies to take psychedelic plants and those are part of an ethical practice that is, they use these to do something in the world that’s correct, to find the correct path. Um, so it usually involves finding, uh, using this technique to fall back into a larger realm of communication to understand a way forward. So it’s, it’s, it’s done for a reason. Often it has to do with, uh, healing individual people who are sick, finding what the problem is, finding, uh, solutions to communal problems, to even larger problems.

EMILY SENAY: We have some video from one of these ceremonies. I think we can show that now.

EDUARDO KOHN: This is the preparation of ayahuasca by a woman who is very dear to me. Her name is Mukutsawa from the Sapata community of Nanchama Cocha. She’s cutting up and boiling, uh, the Banisteriopsis Caapi vine along with Psychotria Viridis.

EDUARDO KOHN: That’s her son [inaudible], a spiritual leader from the nation and they’re beginning to take the medicine now.

EMILY SENAY: He says in there that the ayahuasca opens a portal of knowledge where everything is interconnected, our bodies, all living things. And this is one of the themes that has already come up a couple of times and is this concept of the dissolution of the ego or this, this oneness, losing the self. Um, Anil, tell us about what, how that might have some neuroscientific underpinnings.

ANIL SETH: It’s, when we think about the self it’s, it’s very easy to take the experience of self for granted. And if we think about perception, we think about consciousness, it’s often tempting to think about this in terms of there’s a, there’s a world out there and we experience it somehow through our senses, sense it. And then we form perceptions and these perceptions are a read out if you’d like that presented to the self, whether it’s the soul or an inner homonculus or whatever we conceive of. We tend to think of the self as the thing that’s doing the perceiving. But what we’re finding sort of independently from, from these psychedelic explorations is that the self is itself a perception. The same mechanisms that allow us to perceive the world are also involved in building up the experience of what it is to be you or me. And that consists of many things, the experience of my body, where it is in space, what is part of my body and what isn’t, uh, my sense of agency and will over events, my identity over time and just as we can use things like optical illusions and fancy things to play around with our, to realize that the way we experience the world is a construction. The same thing applies to the self. And so what we refer to as ego dissolution is a sort of internal disintegration, rearrangement of the brain perceiving, uh, the self. And that’s-

EMILY SENAY: Is this the so-called default mode?

ANIL SETH: That’s, there’s, I think it’s related. There’s, there’s often this um, I think this slide is going to come up at least 600 times this evening. Uh, the default mode network is being asked to do often a lot of work in neuroscience. So this, this is a particular network of brain regions that co-activates typically when you’re not doing anything else and they tend to have an association with just mind wandering, uh, when you’re not focusing on the out, on the outside world. So people associate it with, with self perception more than external perception. Now it’s, it’s definitely a huge oversimplification to say this. That’s where the self is. That’s where the soul is the default mode network. No, however, it’s one of the sort of reliable neuronal fingerprints of the typical experience at integrated selfhood, uh, for us every day. And one of the things we can see in the brain in the psychedelic state is a reorganization of the so called resting state networks. These brain regions that tend to show correlations. Um, normally, whether it’s the default mode or another one, we see a reorganization and a breakdown of these typical networks.

EMILY SENAY: Could that be an explanation for the experience, the mystical experience that people have?

ANIL SETH: It’s a step towards that explanation. Yeah. I mean, one of, one of the issues, one of the problems I think we face in, in neuroscience is it’s very tempting to put somebody in a brain scanner and then you see an area light up, or maybe even a few areas in the network and say, ah, that’s, that’s the area for jealousy. That’s the area for right wing political beliefs. That’s the area if you like tabasco. And that is, you know, that’s, that’s not how it works. Um, there are neural, I, I’m, I, yeah, as a firm materialist I believe every experience that we have has a basis in the activity of our, of our brain. Uh, but it’s not as simple as associating a single area or a single network with a particular experience. But it does speak to the issue because we can start to see, okay, how does our experience change under psychedelics? And then we look and we see, ah, these sorts of things like the integrity of the default mode network, uh, that in most other manipulations remains intact. I mean, you can see the Intact default mode network even under cases of loss of consciousness. If we start to see these things reorganize and psychedelics, that’s a big clue about how, uh, how to understand the, the distinctive phenomenology of psychedelics.

EMILY SENAY: Um, Stephen, you’re actually looking at mysticism in religious leaders using psychedelics to replicate or reproduce that. Tell us about some of those studies.

STEPHEN ROSS: Yeah, I’m leading the trial at NYU we’re doing in conjunction with Johns Hopkins and we’re administering several sessions of high dose Psilocybin to religious professionals like rabbis and priests and, and um, uh, it’s always the hardest question to answer what we’re doing in our lab because this one is just weird and different. It’s not a therapeutic thing they were, they’re not a sick population, but the, the backdrop has to do with this famous uh, there was a famous experiment conducted in 1962 led by Walter Pahnke who was at Harvard. He was a psychiatrist and uh, in the divinity school there. His supervisor was Timothy Leary and he had this idea that psychedelics, he looked at different branches of mysticism and religion and there seemed to be a commonality there. And then he looked at indigenous use of psychedelics. And they seem to like line up in terms of the experience. And his idea was that psychedelics could induce a mystical experience and what would it do to religious trainees? So he took a bunch of religious, uh, trainees. He put them all in the Marsh Chapel in 1962, half got high-dose psilocybin and half got a control niacin. And what he found is that a very high percentage of those that got psilocybin had full blown mystical experiences and they went on to follow these individuals over the next several decades and found that the majority found that one of the most spiritual and meaningful effects of their lives that informed, um, you know, the practice as a religious scholar. In our, uh, work with psilocybin in cancer we found that the mystical experience actually mediated some of the effects, the antianxiety antidepressant effects of psilocybin.

STEPHEN ROSS: There was an older literature that suggested that. And so we’re trying to see if religious professionals, given their background, perhaps in experience, uh, altered states or spirituality, can they make nuance discriminations about the mystical experience? Can we learn something qualitatively about their experience? And the other more complicated thing. And I have no idea whether this will actually have any effect on religion. Ultimately, we’re not doing this at any way to try to like dismantle organized religion. We’re just, um, we’re just looking. Uh, you know, the, another way of looking is that it could strengthen people’s faith in religion or it could help people have spiritual experiences that are outside the confines of religion. But the religious professionals we’re, we’re looking to see if they can unpack the mystical experience better for us.

EMILY SENAY: Eduardo, you have spent time in the Amazon again with shamans and, and uh, the indigenous people who are inducing a mystical experience with almost a religious like, um, mission. They have a message, uh, from your experience. Tell us, take us through a little bit of that and what they are trying to tell us.

EDUARDO KOHN: Well, the Shamans that I work with in the Amazon, and this is, uh, an image that of, of a trip we were on just, uh, about 10 days ago. Um, they feel that the Sapata nation is a, is a small nation. They were a much larger nation before the, the rubber boom of the 1920s, the early 1920s that almost decimated their society and their elders say, tell them that, um, that they’re in some ways the spokespersons of the spirit life of the forest to the world. And they have something to say. And in fact, uh, we spent a lot of time talking on that trip to the forest of what I’m supposed to be saying here,

EMILY SENAY: And what is that, what do they want us to know?

EDUARDO KOHN: They want to, they want us to know that, uh, the world we live in is, is a, is a living world where, uh, where mind is in a constant state of emergence, but that world is under threat. And we need to do something to learn to connect ourselves to that. And in some ways, um, if, if we, you know, as individuals may suffer from illnesses like depression, in some sense we’re entering into a planetary depression where our, uh, less expansive forms of thinking are, are leading us to treat these living spaces as resources and not the generation of a kind of emergent mind. And their message is to say, look, these are the, these are places of possibility and to, to, to, to, to continue to have a possibility as a human species. We need to be able to connect with these places and to preserve the possibility of connecting with those places. That’s their message.

EMILY SENAY: Define the shaman and how, how they get to that point, how they’re able to, to convey this message.

EDUARDO KOHN: Well. So shamans are, are an interesting kind of a doctor and psychedelics for them are an interesting kind of a medicine because we usually think of doctors prescribing medicines to patients. Um, psychedelics are generally the kinds of medicines that doctors take. Um, that’s what the, so oftentimes there are many different ways of taking psychedelics in the Amazon but one of the ways is that the doctor, the shaman, takes the psychedelic and the patient is there, uh, being healed by the person who has taken the psychedelic, not necessarily the way that we’re often talking about it here where we give it to the patient, right? Those boundaries are sometimes blurred, but their, their goal is to connect, is to connect with the, with this larger, to fall back to, to let go of some of the structures of thought that they usually hold us to fall back into this much larger realm of possibilities. And, and from there to find a direction forward to see connections we might not otherwise see. And then, to act.

EMILY SENAY: You worked with them to create a soundscape. Let’s listen to that and then you’ll describe what it is we’re hearing.

EDUARDO KOHN: So this is a, a soundscape of, um, deep in the forest. Uh, we’ve made recordings with various tape recorders that, Mati, the spiritual leader has one. I have one. A sound artist has one. And uh, you hear, what you hear are the incredible orchestra of a communicating universe. Um, on top of that, there’s also the shamonic chant, uh, in, uh, recorded during an ayahuasca ceremony. And this is the sort of chamt that sort of holds open the space of possibility in a, in a world that is rapidly dissolving and re, being recreated. On top of that, you also hear, um, thousand year old, uh, archeological instruments that we brought to the Amazon from a museum collection. There’s a, there you can see one of the instruments there. Um, and we are making, um, a soundscape that will allow people to hear how these instruments and what they were used for. These are instruments that were created in rainforest settings to connect with the mind to the forest. Um, and we’re trying to recreate that and allow people to experience that.

EMILY SENAY: One of the things we talked about a little bit earlier, and maybe each one of you can, can talk about this, is that we’re talking about, uh, uh, a sense of oneness, but it can be achieved without psychedelics. Isn’t that so in, isn’t that one of the things that emphasized in the, um, in Ecuador and with children? It’s not only psychedelics that can get us there. Is that fair to say, Allison?

ALISON GOPNIK: Yeah, I think that’s a really important point. So what psychedelics are doing is, is taking advantage of brain chemistry that we know is already there. And part of what that brain chemistry is doing is providing, as Anil said, a much richer range of states of consciousness than we typically think of. Uh, we were at a conference really recently where there was a panel about altered states of consciousness and someone quite sensibly said, what’s the altered supposed to be? Um, you could argue that the state of consciousness I think of as professorial consciousness when we’re sitting there at our desks and focusing very carefully on just one thing. Like that’s a really weird altered state of consciousness compared to most of the consciousness we have most of the time. But I think the more specific thing is that there seem to be these states of consciousness that track the kind of openness and flexibility and plasticity, whether they’re the result of meditation or the result of various kinds of religious practices or have been for a long time connected with the use of these substances.

ALISON GOPNIK: And I think another important thing to say, a point that Eduardo made is that those states of openness just create a possibility. They don’t solve things. What they do is provide people with a set of possibilities and what happens, what they learn, what they experience. Those are the things that actually seem to allow adults or communities to come to solutions or for that matter, children to come to solutions that they wouldn’t be able to come to otherwise. But it depends on what happens. It depends on what you know, it depends on, uh, it depends on what you learn. And that’s very vivid in the case of the substances were what’s called set and setting the context, what’s happening, the integration afterwards, the sense of preparation beforehand. Those all seem to be really crucial to the experience.

ANIL SETH: Yeah. That. That’s right. I think the end of ayahuasca ceremonies often emphasize that’s when the work starts, right? That integration. How do you take advantage of the sense of, of those experiences of the, of the openness, the dissolution, the rearrangement and reorganization that just provides material to, to, to later work with. And yeah, I think you’re right that there are of course other avenues to having different kinds of non-professorial experience, but it’s also I think-

ALISON GOPNIK: But, by the way, my recommendation is have tea with four year olds, just hang out with four year olds. That’s a very, very easy, legal psychedelic experience.

ANIL SETH: But I think it’s also, it’s probably an exaggeration to think that you can attain the same equivalent experience by meditation or by breathing very fast. Well, in my lab we do funny stuff with strobe lights. It’s really amazing to me actually, you shine a fast 10 hertz, very bright strobe light. You sit in front of it with your eyes closed, you will start having visual hallucinations very quickly, but they will not be of the same suit. And in fact, even within the different sorts of psychedelics we’ve been talking about, one of the, the mysteries there is, even though they work on pretty much the same receptor system, the phenomenology can be very different, the phenomenology of ayahuasca can be very different from the phenomenology of LSD or psilocybin. And so yeah, there are multiple ways to get us out of the, the, the, the, the professorial mode or whatever the mode that we’re used to experiencing things. Uh, but, um, but that they do do different things too.

EMILY SENAY: Alison, you have two hats. You are in the philosophy department and in the psychology department, how does psychedelics relate to what a philosopher would think about the mind is, do we need philosophy if we have psychedelics? Can we do away with all of that?

ALISON GOPNIK: Well, we always need philosophy. But I think there’s a, I think there’s a really interesting philosophical question that psychedelics raise, which is one of the impressions that people have. What, what James talked about as the noetic feeling is that the experiences that they have are true. They’re significant, they’re meaningful. They’re not just, you know, crazy hallucinations. And most of the time if we took a substance and we saw things really differently, we’d say, well that’s not real. That’s just a crazy hallucination. And that’s not the phenomenology that people report with psychedelics. So the question is, is there a way in which taking a chemical could tell you something about the truth, that seems kind of contradictory.

ALISON GOPNIK: And I think there’s two important ways in which that actually could be true. One of them is this point about plasticity, about openness, about having a wider range of possibilities. And as I said, what you do with those possibilities, how you make sense of those experiences might vary, but at least being more open to new experiences is an important mode by which people can get at the truth as opposed to being very reliant on the things that you already know. And I think the second point, which connects to something that, uh, that Eduardo said, um, as well, what Anil said is, you know, most of the time we go around with something that as scientists we know is a hallucination. And that hallucination is that there is a little homonculus inside of our head that’s telling us what to do. That’s very separate from the other people around us and very separate from the natural world that there’s this, that the self, the mind that’s in a completely different, uh, is a completely different kind of substance that’s cut off from other things.

ALISON GOPNIK: And as scientists, we know that that’s not true. We know that there’s causal interactions between ourselves and the natural world, that we’re part of the natural world. But to actually feel that as opposed to just kind of knowing it abstractly is difficult. And one of the things that, uh, uh, one of the effects that seems to be characteristic of these substances is to dissolve some of that hallucination. And there’s some sense in which that, you know, one with everything, uh, uh, uh, cliche is actually a better, truer picture of what the world is like than, than the usual hallucination we have about the guy inside of our head who’s telling us what to do.

EDUARDO KOHN: Hallucination is a, is a, is a real hallucination. It’s an effect of how we as humans think, We create a system of, mainly through this, this form of reference, which is language-like based that allows us to, to think ourselves separate from our bodies, to think about tomorrow, to think about something that happened in the Amazon last week, to do all these kinds of things. And that’s wonderful. And that’s what makes us who we are. And yet if we get too much caught up in that, we separate out from the whole rest of the, the thinking metabolisms, the thinking communicative systems that hold us. Um, and I think one of the things that becomes so interesting about psychedelics is they, for a moment they sort of break down that kind of a form of thought much the same way as dreaming does in fact Amazonians um, put as much importance to with, uh, to dreaming as they do to psychedelics because they do similar kinds of things. They allow for another kind of reconnection to many other kinds of thoughts that are less sort of top-down.

EMILY SENAY: Do they define depression or disconnection in, in your experience in the Amazon? Yeah. Do they, do they experience the way we do?

EDUARDO KOHN: I think that, I mean, I think that, um, all humans, they are humans and adults, like everyone else, they live in worlds of language, but they do many kinds of things to break that down. So for example, most of the language that we use are, is a very, you know, we have, we tend to use language in its full capacity. We use words like the word dog means dog in English, but chien is, has a complete different sound in French. Um, their words in Amazonian, the Amazonian languages have many words that are much more imitative that, I mean they also are fully symbolic, but they have this imitative aim, uh, registers to described very precisely things that happen in the world, like the word tsupuh, which means, uh, the describes, uh, uh, body making contact with and penetrating water, right? They have thousands of words like this, which is one way to sort of break down the separation that language creates.

EDUARDO KOHN: And they’re constantly developing these sorts of things. That sort of as a kind of, uh, it keeps things like depression and anxiety at bay if you think of depression and anxiety as ways of living too much in these tracks of thought. But, um, they do see, I mean they have other kinds of what they, we might think of as mental illnesses. They have a kind of illness that people, people, a real illnesses when you can’t dream anymore, when you are an unable to connect with the communicative universe. So hunters who somehow can no longer perceive animals cannot be conscious of other kinds of selves and persons in the forest. Those are the illnesses for them. The, the disconnect from this larger psychedelic world.

EMILY SENAY: Wow. Wow. Alison, you are also a psychologist and if psychedelics mimic a child’s mind, how a child’s brain works, can we as adults use psychedelics to recapture some of that, uh, ability to, that a child’s mind has to learn so easily and to process things and to constantly absorb? Is, is a, is that a realistic,

ALISON GOPNIK: Well, I think, I think it’s important to say that as we were saying before, you know, like you don’t want your department head to be a three-year-old, generally speaking. There’s big advantages to having a sense of self, to being able to project what you’re going to do in the future, um, to being able to narrowly focus your attention away from all the other things that are going on around you. To being able to act in this effective, in this effective way. And you can see this in the course of neural development. So you can see an early brain that’s very plastic that changes a lot where there’s many, many new connections being formed. And then as development takes place, some of the connections, the connections that are used. Yeah. You can see here in the first six years what’s happening is many, many new connections are being formed.

ALISON GOPNIK: And then later on what’s happening is the connections that are used a lot become stronger and more efficient. Um, and the connections that aren’t used are what’s called pruned. Now pruning sounds bad, but it’s actually imperative you have to do that if you’re going to be a functioning adult. So I don’t want to, you know, obviously my sympathies are sort of with the four year olds, but uh, but you, the challenge of adulthood is to be able to do both of those things. And the challenge is that it’s not really possible to do both of those things at the same time. And you need to have social institutions or social devices or individual devices that let you move back and forth from one of those, uh, from one of those states to the other. And these substances seem to serve that function. Moreover, I think there’s a good argument to be made, and Stephen can speak to this, that some disorders like depression and anxiety have the character of being sort of too far in the direction of rigidity.

ALISON GOPNIK: Um, self reflection, self consciousness, rumination for example, is something that seems to play a big role in depression where you’re going over the same thoughts or the same possibilities again and again. And the, the possibility of changing the fact that something might not be terrible in the external world just does, can’t even kind of get in because uh, because of the processes, the kind of rigid processes of an adult and those especially seem to be circumstances as individuals or maybe as societies and communities where these other kinds of practices, uh, can, can help loosen things up.

EMILY SENAY: And talk to us about randomness though. And, and, and how, um, you know, how the, how psychedelics affect neuro, the neuroscience of what’s happening in the brain and affect randomness.

ANIL SETH: Yeah. This, this gets us back to, I think we were talking about a little bit earlier about connecting the dots from what we know about the fine grain pharmacology of psychedelics at the serotonin receptor to their effect on the large scale patterns of the brain that may open up a larger repertoire. I think Michael Pollen has that nice phrase of shaking the snow globe. So you can, you can put the brain in different states that it wouldn’t otherwise be in. One way to try to measure that and to get quantitative about it is to measure, uh, the, the randomness, the diversity of brain activity. This is, I think what’s coming up here as sort of the way we did this in our lab. This is how to put a number on, on the complexity of, of brain activity. This would be something like maximally predictable. I mean you see this repeated pattern of, of ons and offs of blacks and whites.

ANIL SETH: In order to describe a pattern like that that’s so regular, you can do it very simply you just say on, off repeat until the end of time. And that’s, that’s a very simple thing. This is sort of maximally completely random now this is um, like white noise, snow on your TV when it’s not tuned to anything. This is actually the hardest thing to communicate, to transmit. There’s no predictable pattern at all. You have to, you know, to replicate this, you’ve got to replicate every, every point. And most of the, most patterns in nature and most patterns in things that we, we encounter, we’re somewhere in the middle. If we think about what your perception is right now, it’s a mixture of randomness and order and it’s capturing that balance between randomness and order that is quite difficult to measure but be, it’s also at this heart of this balance between explore and exploit.

ANIL SETH: You want to explore, you want to move the needle a little bit more towards randomness. You want to exploit, you want to move the needle a little bit more towards the structure that you already have in place. And so the idea is by using algorithms that actually, the same algorithms that would tell the difference between these three situations here, it’s actually the same algorithm that’s used when you compress an image in your camera and send it by email. We can, we can measure how under psychedelics you are increasing, you’re tipping the dial a little bit more towards diversity and that’s something that is distinctly measurable. I mean the other way to think about it is that under psychedelics also you tend to tip the balance a little bit more towards seeing patterns in things rather than just seeing things as they are. I mean, we can all see faces in clouds.

ANIL SETH: We all have a tendency to project our unconscious or conscious expectations or beliefs out there into the world. I like to think about perception as a kind of controlled hallucination. So all, all projecting things out and getting sensory data back in that refine and restrainer perceptions. And this needle too moves a little bit in psychedelics. This is actually uh, Sussex campus where I work and what we’ve done here is we’ve taken a kind of panoramic video of campus and we’ve used a machine learning algorithm, which is very good at detecting or classifying objects in scenes. It’s one of these so called deep convolutional neural networks. It’s very good. And what we do is we run it backwards. So we tell the network there are dogs and the network then updates the images. And so it’s not like just photoshopping dogs on I mean dogs are coming out of everywhere.

ANIL SETH: The whole thing is suffused by dogs so it’s not actually, there’s dogs in the sky that you know it’s a few too many dogs around there and it’s, I’m not saying this is equivalent to a psychedelic trip, but there are, you know, some people say there are certain similarities and the reason for doing this is A, it’s, it’s a lot of fun but we can use it for open days and things like this come to Sussex, you’ll have fun, but it gives us a way of getting, again, more details. So what might be going on within the brain that specifically leads to the sorts of phenomenology and that if to the extent that that is similar to a psychedelic experience we have, we have a hypothesis from there that what’s happening is again it’s, it’s moving the needle but this time the needle is moved towards, you’re more inclined, you seeing more patterns in things there’s more top down activity in the brain where your, your, your prior beliefs or expectations are overwhelming the sensory data so that you, your controlled hallucinations become a little bit less controlled.

EMILY SENAY: How do you actually measure that though in the brain?

ANIL SETH: Um, this is, this is the challenge. So for measuring just the randomness or diversity?

EMILY SENAY: Yes, randomness.

ANIL SETH: That we can do, we’ve seen that already. There are many ways we can try to measure whether the, there’s more kind of top down projection in the psychedelic brain. Um, this is an MEG scanner. This is where we get some of our data from. We don’t collect it at Sussex. I work with a group at Imperial College in London who collect the data at London Cardiff. Um, but it’s, it’s really it, the short answer is we don’t know yet. I mean we can, we can try to, we have to somehow fit computational models of brain dynamics that, that are doing something similar to that movie that I just showed you of Sussex and see whether those computational models also fit the psychedelic data quite well.

ANIL SETH: There’s an overlap here between what people are doing in what’s now called computational psychiatry. So for instance, in, eh, there’s often an association made and I don’t think it’s a particularly good association between psychedelics and psychosis. I mean, back in, in the beginning of this research, psychedelics were often called, were originally called psychomimetic drugs that they, they were simulating psychosis and, and maybe the extent to which they do is in this hallucinogenic property. And now in computational neuroscience we can build models of how psychotic hallucinations, uh, might be produced by the brain in terms of these expectations having a overly strong effect and we see they fit the data when we put people in brain imaging. And so trying to do that in the case of psychedelics would be, would be one way to approach that question. But we’re very much at the early stages of that.

EMILY SENAY: Very interesting. So we really have to talk about how psychedelics are becoming medicines, treatments for, um, a variety of conditions. Stephen, you’ve really, you’ve taken up the mantle here, you’re really on the cutting edge. Um, this has not been so easy to do, to pick up the thread of psychedelics that were dropped a number of years ago. What, how did you get into it? Uh, where are you now with this? Um, describe a little bit of the, the, the obstacles that you’ve faced when you wanted to explore this.

STEPHEN ROSS: Yeah, I got into this randomly. I didn’t know anything about it. It was like not part of my medical training at all. Zero. It wasn’t part of my psychiatry residency training and it wasn’t part of my, uh, addiction fellowship at NYU. The only thing I heard where some of the urban legends about it and all of the negative stuff. But, um, what I didn’t find out was that they were a huge part of psychiatry. And in 2006, a colleague of mine, just one day started talking to me about ayahuasca. I didn’t know what ayahuasca was, he told me that they were celebrating Albert Hoffman’s birthday, hundredth birthday, and why would anybody do that? And um, so he said no, Psychedelics were, you know, I think they are a big part of psychiatry and you, you didn’t have to look very hard, hidden in plain sight.

STEPHEN ROSS: I couldn’t believe that it was a huge part of psychiatry for about 25 years from the fifties and seventies. There were over 40,000 research participants and what really got me is the most studied indication with the best data was LSD treatment of alcoholism, and me being an addiction expert and alcohol being arguably the worst drug of them all from a public health perspective, that really captured my attention. And um, so, but I thought, well, so what, I mean that’s an interesting thing, but it turns out that psychedelics had restarted in the early nineties, Rick Straussman started it off. Even though Richard Nixon declared war on drugs and enacted the controlled substance act, there was always a route to do research with psychedelics and Rick Straussman got that going. And then Charlie Grove at UCLA and Roland Griffiths at Johns Hopkins, Francisco Marin at University of Arizona started like bringing it back. And Charlie Grove, I went to UCLA for medical school and he really encouraged me in 2006, you should do this and you should do an extension of our psilocybin advanced cancer trial.

EMILY SENAY: But meanwhile that wasn’t so easy practically. Is that fair to say?

STEPHEN ROSS: Well, you have to get what’s called a schedule one license. It took two full years to get the license. It was incredibly difficult. I’ve been working with the DA a long time as the head of our substance abuse division, but there were administrative hurdles. I didn’t think we would get very far. I thought leadership would say no way. But most of the leaders at NYU, um, kept allowing this to go on, except we hit a brick wall at Bellevue, my hospital that I totally love, where the head of the hospital said, we’re not, I’m not going to let you give psychedelics to dying African Americans in this hospital. He cited Tuskegee and just said, we’re not going to get in the media in a negative way. And so I was kind of heartbroken that my sort of beloved hospital did that. But then the NYU dental school reached out to us and I didn’t know we had a dental school at the time. Those dentists, I think that’s the only psychedelics study to ever take place in a dental college.

EMILY SENAY: Wow. Now you’re talking about psilocybin, but a lot of the original research that was mentioned in the introductory package used LSD, but so, so how do you use psilocybin today? What, what happened to LSD?

STEPHEN ROSS: Almost all of the research from the fifties and seventies was with LSD. Very, very little was with psilocybin, but in the modern era, when I looked at the data, I said, okay, we got to start with LSD and alcoholism. The data is incredibly robust there. There was a meta analysis in 2012 of 536 participants between five randomized control trials and it showed there was a clear treatment effect of single dose LSD, but LSD would have been a nonstarter. Those three letters are incredibly evocative. People think LSD, psychosis, jumping off of buildings, danger, bad chromosomal damage, and LSD for alcoholism would have created enormous cognitive dissonance. So there was a strategy to try psilocybin, which is a gentler drug. It didn’t have the political baggage and there was a further strategy to study advanced cancer and people who were dying and there had been an older, that was the second most studied indication after alcoholism so we decided to use psilocybin to treat end of life cancer distress.

EMILY SENAY: Okay. So that’s it. So, so it’s, it’s really a very specific population that it’s been studied in recently, not, not the older studies. And that is, describe what those patients are facing.

STEPHEN ROSS: In the modern era, by far the most studied indication is advanced cancer related psychological and existential distress. There have been three randomized controlled trials between UCLA, Johns Hopkins and NYU, it includes 92 participants. And between the three groups, what we found collectively is that single dose psilocybin produces rapid anti-anxiety and antidepressant effects that were a very large magnitude. In fact, after one day of getting single dose psilocybin, those in the psilocybin group, 80% no longer met criteria for cancer depression, and that endured at seven weeks and at the end, uh, at the end of the trial, eight months later. Compared to the placebo group where there, you know, it was a 20%, uh, had, were in remission. Um, and so we also found that, you know, single dose to last at least seven weeks, but possibly longer than that is, is a kind of breakthrough in psychiatry. We don’t have anything that works rapidly except ketamine. It degrades over a week. So to have something that can work so quickly and last so long, you know, could have enormous benefit. And in addition, we found psilocybin improved quality of life. It decreased existential distress. We measured cancer related demoralization and hopelessness.

EMILY SENAY: I think we have a graph that shows the, that really illustrates pretty well the difference that, that you’re talking about. Um, so tell us what this is.

STEPHEN ROSS: yeah, so, so you can see that the typical antidepressants, if you test antidepressants in the general population of people that have major depression, it’s actually now that a, the data from pharma that was suppressed has been published. It’s the 60% is lower. These are people that are responding, maybe more like 53 and the placebo is a little bit higher, maybe 45. So for severe depression, antidepressants tend to work, for other forms they don’t. Their medicines take a while to work, they have, they can have enormous side effects. Um, in cancer related depression the meta analysis show that the antidepressants don’t work any better than placebo. It’s about a 40%. So if our finding is real that one day after getting it 80% are in remission compared to 40%, if they responded several weeks, um, you know, it could have, um, you know, big implications in the treatment of people, you know, facing end of life distress who are depressed and anxious.

EMILY SENAY: We actually were able to interview two of the participants who were in that study on um, using psilocybin and I think we can take a look at that.

DINAH BAZER: I was diagnosed with ovarian cancer, stage 1C. My first thought was, now I know what I’m going to die of, which couldn’t have been true anyway. You still never know.

OCTAVIAN MIHAI: I felt a lump in my neck that came out positive for Hodgkin’s lymphoma.

DINAH BAZER: My life was just consumed by fear that this is coming back.

OCTAVIAN MIHAI: Things just really spun out of control.

DINAH BAZER: I was given the psilocybin.

OCTAVIAN MIHAI: I took the pill.

DINAH BAZER: I was in a space where nothing existed except me.

OCTAVIAN MIHAI: I became aware that this is probably what death would feel like. I’m still with my soul, but I’m not here anymore and it sort of gave me a lot of confidence because it really wasn’t that bad. It kind of gave me peace of mind because I had such a tremendous fear of this unknown that was death.

DINAH BAZER: I saw a large lump under my ribs and it was not the cancer. It was my fear. I just screamed (bleep) you, who the (bleep) do you think you are? Get Out. It was my real fear and it went away. I banished it.

OCTAVIAN MIHAI: I saw this black smoke come out of my body in like a mushroom cloud. I was thinking from now on, there is no more fear of death or cancer to terrorize me. I’m healed. I have everything to look forward to.

DINAH BAZER: And then I started to have very deep, deep feelings. The only way I could describe it, even though I’m an atheist and I still am, was just bathed in God’s love.

OCTAVIAN MIHAI: It was untainted. It was just pure happiness, pure harmony. It’s beautiful. I felt a different reality. It’s almost like hope.

EMILY SENAY: we actually have Octavian Mihai and Dinah Bazer here this evening, I think right up here in the front row, you’re both here? Octavian, where are you now? How are you doing? Thank you for coming and sharing your story.

OCTAVIAN MIHAI: Yeah. Thank you for having me. Uh, I’m doing great. Uh, my cancer is cured basically. It’s been over five years now. Yeah and I feel incredible. I mean, I haven’t had any more anxiety. Um, I’m just living life normally.

EMILY SENAY: And do you credit that with the, the drug?

OCTAVIAN MIHAI: Absolutely. I mean it, it basically all ended the moment the session ended.

EMILY SENAY: And it never came back?

OCTAVIAN MIHAI: No.

EMILY SENAY: Amazing. Really amazing. Dinah thank you for your explicit honesty in the piece. How are you doing?

DINAH BAZER: Um, I’m doing great. I have other anxieties. I mean, the state of the world is not really what I would wish for my grandchildren.

EMILY SENAY: Well, we’ve all got to work on that though.

DINAH BAZER: I’m not afraid of cancer. I have not been since that experience. It’s been nine years for me since I was diagnosed and treated. So I’ve been in remission all that time. And um, I was suffering such terrible fear and anxiety for the two years until I had the psilocybin. And I just, I just don’t think about it anymore. I don’t think about cancer. I don’t think about, I had ovarian, I don’t think about that coming back. I’ve had a few little episodes where I had genuine concern for my health and I went to the doctor and had it checked out and I was fine, and I didn’t freak out, you know, it was just, well, let’s just see what this is. So very, very different.

EMILY SENAY: Had, had you tried other therapies before this?

DINAH BAZER: I had not, except maybe eating a lot of candy.

EMILY SENAY: And you credit it as Octavian does with the single dose.

DINAH BAZER: Absolutely. Yes. Yeah.

EMILY SENAY: And what would you say to someone in your, in, in a position such as you, or who were, who was having the types of thoughts you were having?

DINAH BAZER: I wish that this drug were available therapeutically. Absolutely. And I know people that are in that situation now and I really feel for them and I wish they could have this.

OCTAVIAN MIHAI: Yeah, I agree with that. I actually, um, before I tried this, I actually tried Xanax, which was the typical thing. Someone, you know, the doctor was prescribed to me, uh, to kind of like help me with the anxiety and I have to say it really wasn’t working. Yeah. Except for those like six hours or so while it was in my system. After that, I would just wake up and it would all just be back to normal. So, um, yeah, that’s, that’s something I tried and that really didn’t work. So I really think that it would be important for this to, to become available because it’s pretty much, in my opinion, the only thing that’s actually getting to the cause of the problem.

EMILY SENAY: Thank you both so much. Really very interesting. So, so right now the most of the research currently being done that’s finished was in patients who had cancer. Is that correct? But we know that there are many other conditions such as, you know, PTSD, alcoholism, opioid abuse, um, and of course depression itself. And I think we have a graph here that shows, um, exactly how common it is. 300 million people globally. Uh, the World Health Organization says it’s a leading cause of disability worldwide and just here in the US it costs $210 billion annually. So when we’re talking about rolling out these drugs and looking at these different, um, conditions, if you can, for depression, where are we with using these drugs in depression, on not just in depression related to cancer and opioids and alcoholism and PTSD, so on and so forth. Can you break that down?

STEPHEN ROSS: Yeah, there’s a big push now to develop psilocybin to treat major depression. It’s uh, 10% of the US population. It’s one of the biggest causes of global disability. And, um, the, the data from the cancer work was taken up by several companies. One is the Usona Institute, the other is Compass and they’ve gone to regulatory agencies. In fact, the FDA has granted compass breakthrough status to study psilocybin and treatment resistant depression. The only data was a small trial done at Imperial College by Robin Carhart-Harris that didn’t have a control group. So the data on depression’s very small, it potentially is very promising in that area and we’re about to be involved in a multicenter trial using psilocybin to treat major depression. And um, I think that it’s a great idea to sort of go in that direction. What I like about psychedelics is that they are being tried on very difficult to treat disorders that do not have good treatments and of life existential distress.

STEPHEN ROSS: There is zero pharmacologic treatments for that. The treatments for depression tend to not work that well. They have lots of side effects. Addiction is in the other areas I mentioned. Um, the most studied indication was alcoholism with the LSD. In the modern era, um, that’s been taken up by our group at NYU, uh, is doing a trial that by Michael Bogenschutz using psilocybin assisted therapy to treat alcoholism. We’re almost done with, with that trial another, uh, 20 participants to go. And we’d done it about a year. Matt Johnson’s leading a trial at Johns Hopkins using psilocybin to treat tobacco addiction. That trial, it’s also nearing the end. There’s a trial at the University of Alabama lit by Peter Hendricks studying psilocybin to treat essentially crack cocaine addiction in African American individuals. And there’s promising data there. There’s a trial at the University of Madison, Wisconsin that just started, about to start using psilocybin treat opiate addiction. And our lab is also moving in the direction of opiate addiction as we have this horrible crisis. So there’s so many different directions to go and it keeps opening up. Hopkins a has designed a trial using psilocybin to treat anorexia, the most fatal psychiatric condition with no medications. So it’s, there’s so many different directions to go therapeutically. Um.

EMILY SENAY: So we’re at the beginning. Would you say?

STEPHEN ROSS: We’re at the beginning, but I predict over the next five years, psychiatry will be radically transformed because I think I would predict in three to five years MDMA will be rescheduled and made available for PTSD. And I think psilocybin soon after that, so in five years, um, you know, practitioners will be able to use ketamine, MDMA and psilocybin in highly regulated settings for very difficult to treat disorders and I think that will radically change psychiatry.

EMILY SENAY: Well, I want to come back to deliver a few key caveats on, on what we’re talking about, but Eduardo I want to ask you a question. You have seen this in a very different setting. Does it surprise you at all that, that psychedelics are now sort of, uh, possibly becoming key treatments for some of the major illnesses that were, we have.

EDUARDO KOHN: No, it doesn’t, it doesn’t surprise me at all. I mean, I think psychedelics, one can see the potential of them even in, in traditional settings. Um, you can also see that, um, that, you know, I think there, there are lots of things that are interesting that are happening here. One, there is a, uh, a fascination with psychedelics, right? Um, there’s of course the hard scientific interest in them because of all the reasons you’ve laid out, but we’re also sort of fascinated by this thing and I think that that fascination with psychedelics, although in many ways positive is also, is also a symptom of something. It’s a symptom of a kind of disconnection that we feel and I don’t necessarily feel that taking psychedelics is the cure to it. Something else. It’s finding other ways to be connected. So I see, I see, uh, possibilities and risks at the same time.

EMILY SENAY: Um, Denver recently decriminalized magic mushrooms, there is a trend, uh, to so called micro-dosing, apparently popular in Silicon Valley and on Wall Street, uh, where I guess, do they call them yuppies still? I don’t know. Um, um, use this to sort of get ahead, get an advantage. They’re more creative but, but I think I need to ask each of you there. This is first of all, what are the risks involved in psychedelics and how really should they be used? Um, should people freelance on this stuff now? What’s your, what’s your take on it? Eduardo, I want to start with you.

EDUARDO KOHN: Well, I, I’d like to go back to that video that we saw at the very beginning. In some ways the reason why psychedelics are so threatening to society. In some ways is a positive thing. Um, they do, they can disrupt the order and there is something wrong with the order today. It’s interesting that the Amazon, um, is a, is an area politically that has never been fully under the state. And it’s interesting that Amazonians are coming up with solutions for problems that in some ways are created, have been created by states, uh, the environmental crisis, the climate change. So there’s something interesting, uh, disruptive about psychedelics, which I think we have to in some ways accept even though it is a dangerous game. Um, but I think there are other, there are many dangerous, I mean there’s a, there’s a real problem with, uh, in the Amazon of ayahuasca tourism, this fascination with this leading people to go into the Amazon disrupting traditional-

EMILY SENAY: Meaning people traveling there. What, what is that exactly?

EDUARDO KOHN: Ayahuasca tourism is a, is a phenomenon. It’s very strong. It’s much stronger in Peru than it is in Ecuador with a lot of people searching for, feeling that this is the solution to their problems and bringing lots of problems to those areas because of that. Now of course, um, Amazonian folks who deal traditionally with the ceremonial use of these plants are not stingy about this. There are moments and places where it’s important for them that other people can be open to this, but it has to be done on their terms. And, uh, this is not, um, something that can be done that’s sort of at a mass scale.

EMILY SENAY: Yeah. I find that the tourism really interesting, Alison, thoughts on, on, um, how they should be used, how we should look at it. And also some of your caveats regarding what it means to have a child like mind and obviously separating out that none of this is being used in children at all. Um, explain, explain the difference there that we’re talking about.

ALISON GOPNIK: Yeah, so I think, I think a theme that comes up again and again is that, um, I mean there are some specific dangers. People who are prone to psychosis for instance, can have very negative experiences. Um, um, so it is extremely important that people be screened beforehand. Um, I think both in the kinds of settings that Eduardo was talking about and in the kind of settings that Stephen is talking about, the preparation beforehand and the integration afterwards and the fact that this is happening in a controlled kind of way is, is absolutely crucial for, uh, for it to, to have positive effects rather than negative effects, rather than to have risks. But also I think that the, the point is of the point of opening up these possibilities is then to do the adult work of actually implementing something that’s different. Of actually changing and having possibility as we know.

ALISON GOPNIK: I mean, children are wonderful because they’re open to possibilities, but they can have experiences that shape them in wonderful ways and they can have experiences that shape them in, in terrible ways too, um, and I think that’s true as well for adults in these circumstances. So figuring out what the right kind of cultural tradition, and part of the trouble is, we don’t have good cultural traditions for, for dealing with, uh, for dealing with these substances or for dealing with these experiences in general. And I think there’s some anxiety that what happened in the 60s could happen again because we don’t have the right kinds of contexts and traditions to, to, to make these things happen. And the kind of therapeutic uses that Stephen is talking about are a really good model for very careful and controlled kinds of, uh, kinds of uses of the substances.

EMILY SENAY: Uh, Stephen, I’ll ask you, there are some contraindications. Um, if people are listening to what we’re talking about tonight, tell us what some of those are regarding other medications they might be taking.

STEPHEN ROSS: Yeah, psychedelics are definitely not for everyone. They’re not miracle magic drugs that should be used by everybody. Um, they have real risks. There are some medical risks. So psilocybin is remarkably safe from a physiologic perspective, um, although it can mildly increased blood pressures. So we really, we rule out people with hypertension or you know, history of serious heart problems. Um, the main problem, the adverse effects are in the psychological realm. Uh, as Alison was saying, these are not drugs that people with psychosis should be taking. They can exacerbate psychosis or occasion the first onset of psychosis in a teenager that were to use it. So, uh, we rule those people out. They’re not for people that are psychologically unstable. Um, and so you really-

EMILY SENAY: Other medications?

STEPHEN ROSS: There can be medication interactions. I mean, so for instance, I don’t think many people know about this. All these people going to use ayahuasca who are on antidepressants, um, antidepressants, serotonergic antidepressants and ayahuasca can interact to cause a condition called Serotonin Syndrome because there’s an MAO inhibitor. And so I, I worry that if people get the idea that psychedelics, they can use them even if they’re trying to use them medicinally. Um, outside of a kind of structured therapeutic setting, I think bad things can happen and I, and I agree that history could repeat itself. This could go from miracle drug to demonic drug and I think we have to look to the history of all this so that we’re careful to not repeat the same mistakes.

EMILY SENAY: Anil?

ANIL SETH: I think the thing that’s coming out is freelancing is probably not the best way to approach, uh, the renewed interest in psychedelics. I mean if I, if I think on the, on the positive side if I project a few years out into the future, I really can see both in the basic science sense that research with psychedelics becomes a core part of our attempts to understand perception, consciousness and self in general, part of the toolbox that one of the most important parts of the toolbox that we can use to systematically manipulate, uh, conscious experiences and then study the neurobiological basis of that. And then in the clinical realm too, I mean I just to echo something that Stephen said, typically if you’re trying to find a pharmacological treatment for something, there are three criteria that you think about. Is it toxic, is it going to kill you? Is it addictive?

ANIL SETH: Does it affect the system in question? You want the answer to the first two questions to be no and the third question to be yes, and the psychedelics ticks all those boxes. Plus there seem to be plausible mechanistic reasons why it might have an effect. So for something like depression was mentioned, depression can be characterize to some extent as repetitive ruminative thinking. So the idea that you can open up new ways of thinking, break the ruts, shake the snow globe. That’s at least a plausible starting point. It’s of course not a fully fledged theory of the psychopharmacology of depression, but it’s a starting point. And the fact that maybe you only need one trial rather than loads. I mean that’s another great point. Of course, this is also why the pharmaceutical industry has been less, maybe not so keen. We can’t make many money out of it for Christ’s sake.

ANIL SETH: You want a drug that costs a lot, that people take every day. That’s not the psychedelic way. So I think there’s a lot of positives, but uh, as well as the pharmacological interactions, I think, I just want to echo this thing about ayahuasca and SSRIs, uh, it’s, it’s really important that, that those do interact but set and setting is, is critical. And so yeah, the back to where we started, the signature effect of psychedelics is that the malleable way with which they affect our experiences of the world and the self. You can take an antibiotic, it doesn’t matter what you take, it’s going to have the same effect on your system. Maybe much the same for some other psychoactive drugs, but the effects of psychedelics depends so much on the context you’re in. Which is why we have the, the shamans in the Amazon. Why we have the white coat shamans in the psychedelic trials of Stephen, to be guided through these experiences in a way that allows you to integrate them later on after the event. That’s where the risks, that’s where the caveats are. That’s why freelancing is not so good but done the right way. I, I’m really excited about, uh, where we might be in a few years time.

EMILY SENAY: Give me, give me your, your picture of a few years from now. Where do you think this is going?

ANIL SETH: In the neuroscience I think we’ll have connected the dots a lot more as Alison said we’re at the beginning. We know the pharmacology and we know to phenomenology and some of the large scale stuff we would be able to answer one of the questions you asked me earlier about for instance, how is it, why is it that the psychedelics have the specific effects they do on, on phenomenology, on the dissolution of the ego, on seeing patterns in clouds or, or, or, or, or seeing life where we don’t experience in the connectedness of all things. We’ll be able to connect those dots much more, much more, um, strongly. And I do think that barring some disaster barring some overreach, which causes the whole thing to be shut down again, there are increasing numbers of groups, uh, having, getting licenses to try well-controlled clinical interventions and I see that becoming much more embedded, much more widely available. I think that the application to depression, uh, will become a big, a big focus and I’m pretty positive.

EMILY SENAY: You had a message to deliver from the, from your travels. Can you repeat that message and tell me where you think things are going to be in the next few years?

EDUARDO KOHN: The call from the Amazon is to live psychedelically, which does not necessarily mean taking psychedelic drugs. It means living in full recognition that what life is about is to be in a state of emergent mind, connecting with the emergent mind that holds us and to learn that that’s where, that’s where that life force comes from. That’s the message that they’re wanting to transmit.

EMILY SENAY: Alison, project into the near future where, where do you see this going?

ALISON GOPNIK: Well, I think as Anil said it holds tremendous promise for actually understanding things that have been challenging forever in cognitive science. Like a understanding how consciousness works. Understanding this very basic question of how our experience is connected to what’s going on in our minds, in our brains, understanding the sort of computers that are inside of our skulls. But I also think that there’s at least potential for both clinical changes and perhaps for changes in our attitudes towards things like our relationship to nature. Which seem like particularly important attitudes to change at this particular, at this particular point in our history. And I should, I should maybe add, we have the great hope that we have new generations of children, new grandchildren who are, who are showing up, who just independently will give us the possibility of making those connections and making those kinds of changes. And I think you can already see that. You can already see that happening.

EMILY SENAY: Stephen, are we going to be writing prescriptions for these in the next five years? Are we going to see a major revolution in, um, treatment of mental illness with the psychedelics?

STEPHEN ROSS: I think so. I, I, we need to do more research. We need to replicate these findings. They’re almost too good to be true. And so we have to do, you know, really good science and then follow the data to find the truth. But my prediction is that the terminal cancer work will put psilocybin over the line within the next five years, the FDA is incredibly open to all of this. And, um, I think depression and addiction in parallel also gonna get, get close. Um, if it’s rescheduled, you’re not gonna be able to go to CVS and get it, they’re gonna be mandated through the FDA, through the REMS program that can only be used in licensed clinics by licensed therapists. We, I created a NYU psychedelic psychotherapy training program about a decade ago because it’s such a unique form of training. I think people will have to, you know, go through those. And, um, but I think it will dramatically transform psychiatry. I think it will transform the care of dying people who have this demoralization, existential distress that have nothing and die in a sort of pain and a horrible death that, that, that’s my biggest hope for it. Um, in terms of the, the cancer work that we’ve done, but I, I’m very hopeful to transform the care of addiction as well.

EMILY SENAY: Terrific. I want to thank Eduardo, uh, Alison and Anil and Stephen for this discussion this evening. Thank you all for coming.

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Revealing the Mind: The Promise of Psychedelics

Nearly every culture throughout history has used chemicals that alter consciousness for spiritual exploration. In the 20th century these drugs caught the attention of scientists. Psychedelics, as they were named, proved effective at treating intractable illnesses like depression and addiction. And they became a tool for studying the mind, opening “the doors of perception,” as Aldous Huxley wrote. But those doors slammed shut when President Nixon declared psychedelics dangerous and medically useless. Join scientists and “psychonauts” who are now picking up where research left off 50 years ago, experimenting with LSD, psilocybin, DMT and other psychedelics to heal—and reveal—the mind.

This program is part of the Big Ideas Series, made possible with support from the John Templeton Foundation.

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Moderator

Emily SenayPhysician Journalist

Emily Senay is a physician, medical and public health educator, broadcast journalist, and author. She is an assistant professor of Medicine in the Department of Preventive Medicine at the Icahn School of Medicine at Mount Sinai and a clinician in the World Trade Center Health Program in New York City.

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Participants

Eduardo KohnAnthropologist

Eduardo Kohn is associate professor of Anthropology at McGill University. He studies the intimate relationships that the indigenous peoples of Ecuador’s Upper Amazon have with one of Earth’s most complex ecosystems.

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Anil SethNeuroscientist, U of Sussex

Anil Seth is Professor of Cognitive and Computational Neuroscience and Director of the Centre for Consciousness Science at the University of Sussex. He is also Co-Director of the Canadian Institute …

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Alison GopnikPsychologist

Alison Gopnik is a professor of psychology and affiliate professor of philosophy at the University of California at Berkeley. She is a world leader in cognitive science, particularly the study of children’s learning and development, and the author of over 100 journal articles and several books.

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Stephen RossAddiction Psychiatrist

Dr. Stephen Ross researches the therapeutic application of psychedelic treatment models to treat psychiatric and addictive disorders. He is an expert in psycho-oncology and is studying novel pharmacologic-psychosocial approaches to treating psychological and existential distress associated with advanced or terminal cancer.

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Transcription

EMILY SENAY: Welcome everyone, I’m Emily Senay, tonight’s moderator. You just saw these quotes from these noted actors, musicians, authors and scientists, and they all credit psychedelics with providing them profound insights, really life changing insights. And as Oliver Sacks said, he once wrote, that psychedelics revealed to him what the mind was capable of. And in fact that’s the definition of psychedelics, the modern definition, meaning mind and soul revealing. Well these chemicals have actually been part of the human story for much longer than recent times, way before scientists elucidated their chemical structures or even named them. So tonight, before we meet our panelists and get into the discussion, let’s get a little introduction to this long, strange trip.

MICHAEL POLLAN: Humans have been using plants and fungus to change the experience of consciousness for a very long time.

NARRATOR: 9,000 year old cave paintings depict rituals with psychedelic mushrooms.

MICHAEL POLLAN: Psychedelics are often used in religious ceremonies as sacraments for divination and healing.

NARRATOR: It wasn’t until the mid 20th century that science got with the program. Early psychedelics research transformed neuroscience. We began treating five patients for 26 days. In clinical trials, psychedelics like LSD showed extraordinary potential. It’s an important drug in treatment of mental and emotional disorder. These substances rose from obscurity to miraculous promise in a matter of years. Dangerous and deadly, disastrous consequences.

MICHAEL POLLAN: All of a sudden there are these scare stories in the media.

NARRATOR: Bizarre, fatal accident, permanent brain damage.

MICHAEL POLLAN: Hyped by the government. There’s propaganda.

NARRATOR: Suicide, chromosomal abnormality. Psychedelics were soon perceived as a threat to public safety and global stability. It’s very dangerous, a very dangerous drug. President Nixon went to the narcotics bureau today to sign a drug bill.

MICHAEL POLLAN: And by the early seventies essentially the research has stopped.

NARRATOR: The golden age of psychedelic science was over. But this story began in 1943.

MICHAEL POLLAN: A young Swiss chemist name Albert Hoffman is working at a pharmaceutical company in Switzerland.

NARRATOR: Tasked with formulating a new stimulant. Hoffman quite inadvertently opened Pandora’s box.

MICHAEL POLLAN: He accidentally ingests what they called LSD 25, got it on his finger, maybe in his eye and started feeling strange and he realized there’s something psychoactive in this one.

NARRATOR: Three days later, he ingests some intentionally.

MICHAEL POLLAN: And realizes like, Oh shit, I’m losing it. Hoffman was having the first acid trip in the world. So he and his lab assistant take one of the most famous bicycle rides in history to his house where he is separating from his body, he’s seeing himself from the ceiling. Then he stepped out in his garden and everything looked jeweled with dew as if it were the first day of creation. And that is how LSD was discovered, commemorated on the April 19th as bicycle day.

NARRATOR: Sandoz, the company Hoffman worked for, provided LSD 25 for free to scientists around the world.

MICHAEL POLLAN: They basically unleashed this open source research effort where they offered huge amounts of it to any researcher basically with a nice piece of stationary. It was LSD that catalyzed our understanding of neurotransmitters and receptors and also the development of other psychiatric drugs.

NARRATOR: Clinical researchers investigated LSD as a treatment for a wide range of mental illnesses.

MICHAEL POLLAN: They looked at obsession, anxiety, depression. They looked especially at alcoholism and had a 50% success rate, which is quite remarkable.

NARRATOR: Psychedelics became a standard tool in psychotherapy.

MICHAEL POLLAN: It would help people speed the process of bringing their subconscious to where you could discuss it where the therapist. There was a lot of this going on in the fifties.

NARRATOR: There was a dark side to the research as well, both the military and the CIA saw great potential. The squad are drugged with LSD.

MICHAEL POLLAN: The CIA got very interested. First they thought LSD might be a mind control agent or a truth serum. Then they thought, well let’s weaponize it. Let’s put it in the water supply. Let’s secretly give it to foreign leaders to make them do and say stupid things. So it was one crazy idea after another. Awful, awful stuff.

NARRATOR: But it’s what was happening here at home that doomed this research.

MICHAEL POLLAN: The drugs escaped the laboratory, and then Timothy Leary gives them a big push.

NARRATOR: Harvard psychologist, Timothy Leary, developed a dubious curriculum of mind expansion and personal truth through psychedelics.

MICHAEL POLLAN: A scandal erupts. He’s fired from Harvard and then decides to become the LSD evangelist. Turn on, tune in and drop out. He’s essentially saying everybody should use this drug. And the drug is taken up by the counter culture. Richard Nixon was convinced that he was dealing with a threat from psychedelics. He called Timothy Leary the most dangerous man in America.

NARRATOR: The kids who take LSD aren’t going to fight your wars, they’re not going to join your corporations. And here Timothy Leary and Richard Nixon were in agreement.

MICHAEL POLLAN: So Nixon passed the controlled Substances Act in 1970 and that listed psilocybin and LSD as no accepted medical use and a high potential for abuse, neither of which are true. And that’s a remarkable event in the history of science. I don’t know that you can point to another time or episode where you had a very promising line of inquiry that is simply stopped for reasons that have nothing to do with the science. And we lost 30 years of research. Imagine what we would know now had we been studying these compounds for those 30 years. What we might’ve learned about depression, anxiety and addiction, consciousness and how the mind works.

EMILY SENAY: Let’s meet our panelists.

EMILY SENAY: Our first participant is a psychiatrist working to find better treatments for some of the most debilitating illnesses affecting human beings including depression, anxiety, and addiction. Please welcome Stephen Ross

EMILY SENAY: Our next participant studies the brain and the mind. Professor of cognitive and computational neuroscience at the University of Sussex in England. He has published more than a hundred papers on the nature of consciousness and the self. Please welcome Anil Seth.

EMILY SENAY: Our next participant wants to understand how babies think and what that reveals about all of us. Professor of psychology and philosophy at the University of California at Berkeley and author of the bestselling book, the philosophical baby, please welcome Alison Gopnik.

EMILY SENAY: Finally, please welcome a researcher whose ethnographic field work has brought him many times to the Amazon Rainforest. Associate professor of anthropology at McGill University in Montreal, Eduardo Kohn. So welcome everyone, and I think we need to start with understanding what we’re talking about here. And Stephen, I’m going to task you with this to define if you can, what are psychedelics? We know they’re not marijuana. We know they’re not opioids. What are they? How do we define these drugs?

STEPHEN ROSS: Well, they’re a group of drugs that profoundly alters consciousness. They do it all by activating the subtype of Serotonin receptor, the 2A receptor. All of them do that. If you block that receptor, they don’t have any psychoactive effects. And they’re unusual compared to the other drugs of abuse in that they don’t meet the definition of an addictive drug. And they’re not addictive. In fact, if anything, they have a potent anti-addictive, uh, potential.

EMILY SENAY: And what are the names of some of these drugs? Would we know them as LSD, psilocybin? Is there a list that qualifies as a psychedelic?

STEPHEN ROSS: Well, the serotonergic hallucinogens or psychedelics, there’s two different sub categories. There’s the Indolealkylamines, these are drugs like LSD, psilocybin, and DMT. DMT is found in ayahuasca, and they look remarkably similar to the endogenous neurotransmitter Serotonin. And then there’s the phenylethylamines and the prototypical here is Mescalin and these are more amphetaminergic psychedelics and their ring structure very closely resembles norepinephrine.

EMILY SENAY: So, so they work on those receptors in the brain, is that correct?

STEPHEN ROSS: All of them have a commonality of activating the 2A receptor and that what’s lead, that causes their unusual psychological properties.

EMILY SENAY: Okay. We hear a lot about other drugs like MDMA, which is also known as ecstasy and also ketamine. Where do these fall into the psychedelic classifications.

STEPHEN ROSS: Ketamine is probably the closest phenomenologically to psilocybin but it has a much different mechanism, it blocks a type of glutamatergic receptor, the NMDA receptor, and it profoundly alters consciousness too, but it’s also a dissociative anesthetic. But there are commonalities in terms of the experience and the brain function of ketamine versus psilocybin. Ketamine is actually the first psychedelic that’s available as a medicine for a treatment resistant depression. Uh, it recently was, was approved Janssen pharmaceuticals. MDMA is psychedelic-like, but it’s a very complex drug. It’s being used to treat PTSD. There’s, it has breakthrough status with the FDA and probably will be made available as a medicine in the coming years for complex PTSD and it has a host of effects. It affects the serotonergic system. It causes increase in signaling Serotonin and dopamine. It actually has some addictive properties. It also releases oxytocin and causes this sort of bonding feeling and it also deactivates the amygdala, so it puts people in a kind of altered state where they feel bonded and a sense of trust. And in the MDMA PTSD research they’re able to then go back and talk about the trauma and maybe sort of like rewrite it neutrally.

EMILY SENAY: So if we could very, in a very pithy way, define the difference between what makes a psychedelic and some other drugs like marijuana or or opioids. Is there a central feature of the experience that defines psychedelic? Anybody can jump in on this. Is there, how would you characterize the experience that makes that unique? That says that’s a psychedelic,

STEPHEN ROSS: well, the, the terminology is not great. Psychedeila, psychedelic means mind manifesting. It’s unclear what that means, but the commonality is that they all essentially dissolve the sense of the ego and they can create a sense of oneness. They’re consciousness expanding drugs and they, they do it quite potently.

EMILY SENAY: Anil you, you say these drugs do something that no other drugs do. Can we talk about what that is and this is actually the neuroscience of how they function.

ANIL SETH: Yeah, there is a difference. And I think that the big interest is we, we know quite a lot as Stephen has said about the pharmacology of the psychedelics, but the effect on the phenomenology and how we experience the world and the self is really what’s striking, what’s distinctive. And if, again, if you compare it to other classes of drugs, you have things like marijuana, which gives you this comforting haze. You have cocaine, which gives you a laser focus. You might have the morphine, which gives you a rush of pleasure and psychedelics don’t do any of these things. They work more on your perception. And people often talk about an initial sense of discomfort as sort of patterns, normal patterns of perception of the world and the self are broken down and then there’s this, the phenomenological effect seems to be that you really perceive things in a very different way, whether it’s features of the of the external world, you can see patterns and things that that weren’t previously there.

ANIL SETH: You experience yourself in a very different way too and as Stephen said, there’s a breakdown in the categories that often separate the different ways in which we normally perceive things. So we might experience ourself as not the unified separate entity that we do, or at least we think that we do day to day. I mean another question here is that we think we perceive the world and the self in particular ways and maybe we don’t actually do this all the time and that’s the mind manifesting aspect of psychedelics. It can make clear that the repertoire of the ways in which we can have conscious experiences is very much larger than we might typically be aware of, which, which as a, as a researcher whose primary interest is in consciousness itself is why they’re so fascinating.

EMILY SENAY: And, and what is happening in the brain there, there, there is an effect on the brain that increases randomness or, or there’s an effect that you can actually define, is that fair?

ANIL SETH: Well there’s many effects. I mean, this is, I think is why there’s so much work to be done. It’s a very exciting area to be in because we have this big, big explanatory gap, if you’d like. We know that these pretty much all the psychedelics work pharmacologically on the Serotonin 2A receptor. We know where that receptor is distributed. We know there are high concentrations in particular parts of the brain in the visual cortex, in parts of the brain that associate different perceptual modalities. Also in the gut, interestingly. Um, and so we know that and we know the phenomenological effects of these things. Connecting the two, so what are the effects of these targeted pharmaceuticals compounds at the level of, of the brain dynamics and brain organization. That’s what, that’s what’s interesting. And this, uh, this is one example. This is some work that we did in collaboration with a research group at Imperial College London, one of the first groups along with students to study the, these compounds in brain imaging.

ANIL SETH: And what we found in this particular experiment was that the brain on, on psychedelics, this is LSD and psilocybin, uh, becomes more random. That’s to say different, each part of the brain, what you see in this picture is different parts of the brain, the, the redder they are the more random the activity is compared to a baseline of no psychedelic. And this is just one way of saying that on psychedelics, the brain seems to be exploring a larger repertoire of possible states and that may underlie this kind of expanded space of possible experiences that we have.

EMILY SENAY: Amazing. Alison, you look at this from a very different perspective. You understand how a child’s mind works. What he just said relates to some of the things we’ve talked about earlier on before the show in, in how the child’s mind works.

ALISON GOPNIK: Yeah. So one of the things that we know from looking at children and looking at brain development is that we see in the course of development a shift from a brain that looks more like the brain that Anil is talking about. A brain that has more local connections and fewer long distance connections, um, to a brain that an adult brain that’s much more structured and also much less flexible, much less plastic. So if you’re thinking about children, what you see is that you see an early period where the brain and the mind are very good at learning. Very good at exploring possibilities, good at doing things like crazy, pretend play, not very good at putting on your jacket and getting to preschool in the morning and not very good at actually going out and acting effectively. And what cognitive scientists have been thinking about this is that there may be a real purpose for this. It’s not just that the children are sort of defective adults.

ALISON GOPNIK: If you look in areas like, yeah, if you look in areas like artificial intelligence, it turns out that there’s this basic tension between what people sometimes call exploration and exploitation. There’s a basic tension between trying to have any kind of system that’s good at exploring possibility, that’s good at creating new possibilities, new alternatives and one that’s good at focusing and getting things done and acting in the world. And what evolution seems to do is to solve this tension by giving us this long period in our human childhood, it’s longer than any other, where we can just be in this state of very wide ranging exploration. We can be noisy, we can be random, we can do strange things, we can have imaginary companions that seem, that seem vivid and real to us, um, but we don’t have to do very much. And then we can use that kind of exploration as adults to find new possibilities.

ALISON GOPNIK: And one of the challenges of human adulthood is that we seem to have some ways of going back and forth between this adult state of being very efficient but not so flexible and this more childlike state of being very creative and open, um, but not as efficient and psychedelic substances seem to reinduce something like that childhood state. And there’s actually some recent experiments suggesting that at least some of these literally open up windows of what neuroscientists call plasticity, this kind of openness, uh, openness to experience even in adults where normally that kind of openness would be shut down.

EMILY SENAY: Eduardo, you’ve, you’ve spent a lot of time in the Amazon and you say that they’ve somehow managed to achieve a balance between the two tensions that Alison is talking about, flexibility versus openness. Tell us about your experience and what you learned from them.

EDUARDO KOHN: I want to come back to the term psychedelic, which I think in traditional context is quite a, quite inappropriate term. Can think of the term, the etymology, psyche, mind or spirit and deloan, manifesting, revealing, um, Amazonians, um, use a series of technologies, one of which is a psychedelic plant, a decoction ayahuasca, uh, but other ones as well, such as dreaming to, um, to find a way to be in touch with what they consider, uh, the mind of the forest. Uh, uh, the mind-like qualities that one finds in complex living ecosystems, um, and they use that as a form of guidance and they do so in such a way that what they do is they, they kind of break down the sort of normal everyday way of living, uh, uh, adult way of living. You could say, uh, they break down the way in which we kind of get our marching orders from the languages we speak. We have our identity based on the, the way that words hold who we are and they find a way to, to communicate and be in touch with a larger communicative field. Um, part of this is quite practical, like listening to bird calls and walking in the forest and quite, and some of it’s a bit more esoteric, like remembering the interpreting dreams and taking certain psychoactive psychedelic substances.

EMILY SENAY: But they do have, there’s a ritualistic aspect to it. Is that right? And, and, and they don’t, it’s not a, um, it’s, it’s a well thought out program that they have that’s different than what we’re familiar with here. And they do it through a ceremony

EDUARDO KOHN: that’s right there. There are ceremonies to take psychedelic plants and those are part of an ethical practice that is, they use these to do something in the world that’s correct, to find the correct path. Um, so it usually involves finding, uh, using this technique to fall back into a larger realm of communication to understand a way forward. So it’s, it’s, it’s done for a reason. Often it has to do with, uh, healing individual people who are sick, finding what the problem is, finding, uh, solutions to communal problems, to even larger problems.

EMILY SENAY: We have some video from one of these ceremonies. I think we can show that now.

EDUARDO KOHN: This is the preparation of ayahuasca by a woman who is very dear to me. Her name is Mukutsawa from the Sapata community of Nanchama Cocha. She’s cutting up and boiling, uh, the Banisteriopsis Caapi vine along with Psychotria Viridis.

EDUARDO KOHN: That’s her son [inaudible], a spiritual leader from the nation and they’re beginning to take the medicine now.

EMILY SENAY: He says in there that the ayahuasca opens a portal of knowledge where everything is interconnected, our bodies, all living things. And this is one of the themes that has already come up a couple of times and is this concept of the dissolution of the ego or this, this oneness, losing the self. Um, Anil, tell us about what, how that might have some neuroscientific underpinnings.

ANIL SETH: It’s, when we think about the self it’s, it’s very easy to take the experience of self for granted. And if we think about perception, we think about consciousness, it’s often tempting to think about this in terms of there’s a, there’s a world out there and we experience it somehow through our senses, sense it. And then we form perceptions and these perceptions are a read out if you’d like that presented to the self, whether it’s the soul or an inner homonculus or whatever we conceive of. We tend to think of the self as the thing that’s doing the perceiving. But what we’re finding sort of independently from, from these psychedelic explorations is that the self is itself a perception. The same mechanisms that allow us to perceive the world are also involved in building up the experience of what it is to be you or me. And that consists of many things, the experience of my body, where it is in space, what is part of my body and what isn’t, uh, my sense of agency and will over events, my identity over time and just as we can use things like optical illusions and fancy things to play around with our, to realize that the way we experience the world is a construction. The same thing applies to the self. And so what we refer to as ego dissolution is a sort of internal disintegration, rearrangement of the brain perceiving, uh, the self. And that’s-

EMILY SENAY: Is this the so-called default mode?

ANIL SETH: That’s, there’s, I think it’s related. There’s, there’s often this um, I think this slide is going to come up at least 600 times this evening. Uh, the default mode network is being asked to do often a lot of work in neuroscience. So this, this is a particular network of brain regions that co-activates typically when you’re not doing anything else and they tend to have an association with just mind wandering, uh, when you’re not focusing on the out, on the outside world. So people associate it with, with self perception more than external perception. Now it’s, it’s definitely a huge oversimplification to say this. That’s where the self is. That’s where the soul is the default mode network. No, however, it’s one of the sort of reliable neuronal fingerprints of the typical experience at integrated selfhood, uh, for us every day. And one of the things we can see in the brain in the psychedelic state is a reorganization of the so called resting state networks. These brain regions that tend to show correlations. Um, normally, whether it’s the default mode or another one, we see a reorganization and a breakdown of these typical networks.

EMILY SENAY: Could that be an explanation for the experience, the mystical experience that people have?

ANIL SETH: It’s a step towards that explanation. Yeah. I mean, one of, one of the issues, one of the problems I think we face in, in neuroscience is it’s very tempting to put somebody in a brain scanner and then you see an area light up, or maybe even a few areas in the network and say, ah, that’s, that’s the area for jealousy. That’s the area for right wing political beliefs. That’s the area if you like tabasco. And that is, you know, that’s, that’s not how it works. Um, there are neural, I, I’m, I, yeah, as a firm materialist I believe every experience that we have has a basis in the activity of our, of our brain. Uh, but it’s not as simple as associating a single area or a single network with a particular experience. But it does speak to the issue because we can start to see, okay, how does our experience change under psychedelics? And then we look and we see, ah, these sorts of things like the integrity of the default mode network, uh, that in most other manipulations remains intact. I mean, you can see the Intact default mode network even under cases of loss of consciousness. If we start to see these things reorganize and psychedelics, that’s a big clue about how, uh, how to understand the, the distinctive phenomenology of psychedelics.

EMILY SENAY: Um, Stephen, you’re actually looking at mysticism in religious leaders using psychedelics to replicate or reproduce that. Tell us about some of those studies.

STEPHEN ROSS: Yeah, I’m leading the trial at NYU we’re doing in conjunction with Johns Hopkins and we’re administering several sessions of high dose Psilocybin to religious professionals like rabbis and priests and, and um, uh, it’s always the hardest question to answer what we’re doing in our lab because this one is just weird and different. It’s not a therapeutic thing they were, they’re not a sick population, but the, the backdrop has to do with this famous uh, there was a famous experiment conducted in 1962 led by Walter Pahnke who was at Harvard. He was a psychiatrist and uh, in the divinity school there. His supervisor was Timothy Leary and he had this idea that psychedelics, he looked at different branches of mysticism and religion and there seemed to be a commonality there. And then he looked at indigenous use of psychedelics. And they seem to like line up in terms of the experience. And his idea was that psychedelics could induce a mystical experience and what would it do to religious trainees? So he took a bunch of religious, uh, trainees. He put them all in the Marsh Chapel in 1962, half got high-dose psilocybin and half got a control niacin. And what he found is that a very high percentage of those that got psilocybin had full blown mystical experiences and they went on to follow these individuals over the next several decades and found that the majority found that one of the most spiritual and meaningful effects of their lives that informed, um, you know, the practice as a religious scholar. In our, uh, work with psilocybin in cancer we found that the mystical experience actually mediated some of the effects, the antianxiety antidepressant effects of psilocybin.

STEPHEN ROSS: There was an older literature that suggested that. And so we’re trying to see if religious professionals, given their background, perhaps in experience, uh, altered states or spirituality, can they make nuance discriminations about the mystical experience? Can we learn something qualitatively about their experience? And the other more complicated thing. And I have no idea whether this will actually have any effect on religion. Ultimately, we’re not doing this at any way to try to like dismantle organized religion. We’re just, um, we’re just looking. Uh, you know, the, another way of looking is that it could strengthen people’s faith in religion or it could help people have spiritual experiences that are outside the confines of religion. But the religious professionals we’re, we’re looking to see if they can unpack the mystical experience better for us.

EMILY SENAY: Eduardo, you have spent time in the Amazon again with shamans and, and uh, the indigenous people who are inducing a mystical experience with almost a religious like, um, mission. They have a message, uh, from your experience. Tell us, take us through a little bit of that and what they are trying to tell us.

EDUARDO KOHN: Well, the Shamans that I work with in the Amazon, and this is, uh, an image that of, of a trip we were on just, uh, about 10 days ago. Um, they feel that the Sapata nation is a, is a small nation. They were a much larger nation before the, the rubber boom of the 1920s, the early 1920s that almost decimated their society and their elders say, tell them that, um, that they’re in some ways the spokespersons of the spirit life of the forest to the world. And they have something to say. And in fact, uh, we spent a lot of time talking on that trip to the forest of what I’m supposed to be saying here,

EMILY SENAY: And what is that, what do they want us to know?

EDUARDO KOHN: They want to, they want us to know that, uh, the world we live in is, is a, is a living world where, uh, where mind is in a constant state of emergence, but that world is under threat. And we need to do something to learn to connect ourselves to that. And in some ways, um, if, if we, you know, as individuals may suffer from illnesses like depression, in some sense we’re entering into a planetary depression where our, uh, less expansive forms of thinking are, are leading us to treat these living spaces as resources and not the generation of a kind of emergent mind. And their message is to say, look, these are the, these are places of possibility and to, to, to, to, to continue to have a possibility as a human species. We need to be able to connect with these places and to preserve the possibility of connecting with those places. That’s their message.

EMILY SENAY: Define the shaman and how, how they get to that point, how they’re able to, to convey this message.

EDUARDO KOHN: Well. So shamans are, are an interesting kind of a doctor and psychedelics for them are an interesting kind of a medicine because we usually think of doctors prescribing medicines to patients. Um, psychedelics are generally the kinds of medicines that doctors take. Um, that’s what the, so oftentimes there are many different ways of taking psychedelics in the Amazon but one of the ways is that the doctor, the shaman, takes the psychedelic and the patient is there, uh, being healed by the person who has taken the psychedelic, not necessarily the way that we’re often talking about it here where we give it to the patient, right? Those boundaries are sometimes blurred, but their, their goal is to connect, is to connect with the, with this larger, to fall back to, to let go of some of the structures of thought that they usually hold us to fall back into this much larger realm of possibilities. And, and from there to find a direction forward to see connections we might not otherwise see. And then, to act.

EMILY SENAY: You worked with them to create a soundscape. Let’s listen to that and then you’ll describe what it is we’re hearing.

EDUARDO KOHN: So this is a, a soundscape of, um, deep in the forest. Uh, we’ve made recordings with various tape recorders that, Mati, the spiritual leader has one. I have one. A sound artist has one. And uh, you hear, what you hear are the incredible orchestra of a communicating universe. Um, on top of that, there’s also the shamonic chant, uh, in, uh, recorded during an ayahuasca ceremony. And this is the sort of chamt that sort of holds open the space of possibility in a, in a world that is rapidly dissolving and re, being recreated. On top of that, you also hear, um, thousand year old, uh, archeological instruments that we brought to the Amazon from a museum collection. There’s a, there you can see one of the instruments there. Um, and we are making, um, a soundscape that will allow people to hear how these instruments and what they were used for. These are instruments that were created in rainforest settings to connect with the mind to the forest. Um, and we’re trying to recreate that and allow people to experience that.

EMILY SENAY: One of the things we talked about a little bit earlier, and maybe each one of you can, can talk about this, is that we’re talking about, uh, uh, a sense of oneness, but it can be achieved without psychedelics. Isn’t that so in, isn’t that one of the things that emphasized in the, um, in Ecuador and with children? It’s not only psychedelics that can get us there. Is that fair to say, Allison?

ALISON GOPNIK: Yeah, I think that’s a really important point. So what psychedelics are doing is, is taking advantage of brain chemistry that we know is already there. And part of what that brain chemistry is doing is providing, as Anil said, a much richer range of states of consciousness than we typically think of. Uh, we were at a conference really recently where there was a panel about altered states of consciousness and someone quite sensibly said, what’s the altered supposed to be? Um, you could argue that the state of consciousness I think of as professorial consciousness when we’re sitting there at our desks and focusing very carefully on just one thing. Like that’s a really weird altered state of consciousness compared to most of the consciousness we have most of the time. But I think the more specific thing is that there seem to be these states of consciousness that track the kind of openness and flexibility and plasticity, whether they’re the result of meditation or the result of various kinds of religious practices or have been for a long time connected with the use of these substances.

ALISON GOPNIK: And I think another important thing to say, a point that Eduardo made is that those states of openness just create a possibility. They don’t solve things. What they do is provide people with a set of possibilities and what happens, what they learn, what they experience. Those are the things that actually seem to allow adults or communities to come to solutions or for that matter, children to come to solutions that they wouldn’t be able to come to otherwise. But it depends on what happens. It depends on what you know, it depends on, uh, it depends on what you learn. And that’s very vivid in the case of the substances were what’s called set and setting the context, what’s happening, the integration afterwards, the sense of preparation beforehand. Those all seem to be really crucial to the experience.

ANIL SETH: Yeah. That. That’s right. I think the end of ayahuasca ceremonies often emphasize that’s when the work starts, right? That integration. How do you take advantage of the sense of, of those experiences of the, of the openness, the dissolution, the rearrangement and reorganization that just provides material to, to, to later work with. And yeah, I think you’re right that there are of course other avenues to having different kinds of non-professorial experience, but it’s also I think-

ALISON GOPNIK: But, by the way, my recommendation is have tea with four year olds, just hang out with four year olds. That’s a very, very easy, legal psychedelic experience.

ANIL SETH: But I think it’s also, it’s probably an exaggeration to think that you can attain the same equivalent experience by meditation or by breathing very fast. Well, in my lab we do funny stuff with strobe lights. It’s really amazing to me actually, you shine a fast 10 hertz, very bright strobe light. You sit in front of it with your eyes closed, you will start having visual hallucinations very quickly, but they will not be of the same suit. And in fact, even within the different sorts of psychedelics we’ve been talking about, one of the, the mysteries there is, even though they work on pretty much the same receptor system, the phenomenology can be very different, the phenomenology of ayahuasca can be very different from the phenomenology of LSD or psilocybin. And so yeah, there are multiple ways to get us out of the, the, the, the, the professorial mode or whatever the mode that we’re used to experiencing things. Uh, but, um, but that they do do different things too.

EMILY SENAY: Alison, you have two hats. You are in the philosophy department and in the psychology department, how does psychedelics relate to what a philosopher would think about the mind is, do we need philosophy if we have psychedelics? Can we do away with all of that?

ALISON GOPNIK: Well, we always need philosophy. But I think there’s a, I think there’s a really interesting philosophical question that psychedelics raise, which is one of the impressions that people have. What, what James talked about as the noetic feeling is that the experiences that they have are true. They’re significant, they’re meaningful. They’re not just, you know, crazy hallucinations. And most of the time if we took a substance and we saw things really differently, we’d say, well that’s not real. That’s just a crazy hallucination. And that’s not the phenomenology that people report with psychedelics. So the question is, is there a way in which taking a chemical could tell you something about the truth, that seems kind of contradictory.

ALISON GOPNIK: And I think there’s two important ways in which that actually could be true. One of them is this point about plasticity, about openness, about having a wider range of possibilities. And as I said, what you do with those possibilities, how you make sense of those experiences might vary, but at least being more open to new experiences is an important mode by which people can get at the truth as opposed to being very reliant on the things that you already know. And I think the second point, which connects to something that, uh, that Eduardo said, um, as well, what Anil said is, you know, most of the time we go around with something that as scientists we know is a hallucination. And that hallucination is that there is a little homonculus inside of our head that’s telling us what to do. That’s very separate from the other people around us and very separate from the natural world that there’s this, that the self, the mind that’s in a completely different, uh, is a completely different kind of substance that’s cut off from other things.

ALISON GOPNIK: And as scientists, we know that that’s not true. We know that there’s causal interactions between ourselves and the natural world, that we’re part of the natural world. But to actually feel that as opposed to just kind of knowing it abstractly is difficult. And one of the things that, uh, uh, one of the effects that seems to be characteristic of these substances is to dissolve some of that hallucination. And there’s some sense in which that, you know, one with everything, uh, uh, uh, cliche is actually a better, truer picture of what the world is like than, than the usual hallucination we have about the guy inside of our head who’s telling us what to do.

EDUARDO KOHN: Hallucination is a, is a, is a real hallucination. It’s an effect of how we as humans think, We create a system of, mainly through this, this form of reference, which is language-like based that allows us to, to think ourselves separate from our bodies, to think about tomorrow, to think about something that happened in the Amazon last week, to do all these kinds of things. And that’s wonderful. And that’s what makes us who we are. And yet if we get too much caught up in that, we separate out from the whole rest of the, the thinking metabolisms, the thinking communicative systems that hold us. Um, and I think one of the things that becomes so interesting about psychedelics is they, for a moment they sort of break down that kind of a form of thought much the same way as dreaming does in fact Amazonians um, put as much importance to with, uh, to dreaming as they do to psychedelics because they do similar kinds of things. They allow for another kind of reconnection to many other kinds of thoughts that are less sort of top-down.

EMILY SENAY: Do they define depression or disconnection in, in your experience in the Amazon? Yeah. Do they, do they experience the way we do?

EDUARDO KOHN: I think that, I mean, I think that, um, all humans, they are humans and adults, like everyone else, they live in worlds of language, but they do many kinds of things to break that down. So for example, most of the language that we use are, is a very, you know, we have, we tend to use language in its full capacity. We use words like the word dog means dog in English, but chien is, has a complete different sound in French. Um, their words in Amazonian, the Amazonian languages have many words that are much more imitative that, I mean they also are fully symbolic, but they have this imitative aim, uh, registers to described very precisely things that happen in the world, like the word tsupuh, which means, uh, the describes, uh, uh, body making contact with and penetrating water, right? They have thousands of words like this, which is one way to sort of break down the separation that language creates.

EDUARDO KOHN: And they’re constantly developing these sorts of things. That sort of as a kind of, uh, it keeps things like depression and anxiety at bay if you think of depression and anxiety as ways of living too much in these tracks of thought. But, um, they do see, I mean they have other kinds of what they, we might think of as mental illnesses. They have a kind of illness that people, people, a real illnesses when you can’t dream anymore, when you are an unable to connect with the communicative universe. So hunters who somehow can no longer perceive animals cannot be conscious of other kinds of selves and persons in the forest. Those are the illnesses for them. The, the disconnect from this larger psychedelic world.

EMILY SENAY: Wow. Wow. Alison, you are also a psychologist and if psychedelics mimic a child’s mind, how a child’s brain works, can we as adults use psychedelics to recapture some of that, uh, ability to, that a child’s mind has to learn so easily and to process things and to constantly absorb? Is, is a, is that a realistic,

ALISON GOPNIK: Well, I think, I think it’s important to say that as we were saying before, you know, like you don’t want your department head to be a three-year-old, generally speaking. There’s big advantages to having a sense of self, to being able to project what you’re going to do in the future, um, to being able to narrowly focus your attention away from all the other things that are going on around you. To being able to act in this effective, in this effective way. And you can see this in the course of neural development. So you can see an early brain that’s very plastic that changes a lot where there’s many, many new connections being formed. And then as development takes place, some of the connections, the connections that are used. Yeah. You can see here in the first six years what’s happening is many, many new connections are being formed.

ALISON GOPNIK: And then later on what’s happening is the connections that are used a lot become stronger and more efficient. Um, and the connections that aren’t used are what’s called pruned. Now pruning sounds bad, but it’s actually imperative you have to do that if you’re going to be a functioning adult. So I don’t want to, you know, obviously my sympathies are sort of with the four year olds, but uh, but you, the challenge of adulthood is to be able to do both of those things. And the challenge is that it’s not really possible to do both of those things at the same time. And you need to have social institutions or social devices or individual devices that let you move back and forth from one of those, uh, from one of those states to the other. And these substances seem to serve that function. Moreover, I think there’s a good argument to be made, and Stephen can speak to this, that some disorders like depression and anxiety have the character of being sort of too far in the direction of rigidity.

ALISON GOPNIK: Um, self reflection, self consciousness, rumination for example, is something that seems to play a big role in depression where you’re going over the same thoughts or the same possibilities again and again. And the, the possibility of changing the fact that something might not be terrible in the external world just does, can’t even kind of get in because uh, because of the processes, the kind of rigid processes of an adult and those especially seem to be circumstances as individuals or maybe as societies and communities where these other kinds of practices, uh, can, can help loosen things up.

EMILY SENAY: And talk to us about randomness though. And, and, and how, um, you know, how the, how psychedelics affect neuro, the neuroscience of what’s happening in the brain and affect randomness.

ANIL SETH: Yeah. This, this gets us back to, I think we were talking about a little bit earlier about connecting the dots from what we know about the fine grain pharmacology of psychedelics at the serotonin receptor to their effect on the large scale patterns of the brain that may open up a larger repertoire. I think Michael Pollen has that nice phrase of shaking the snow globe. So you can, you can put the brain in different states that it wouldn’t otherwise be in. One way to try to measure that and to get quantitative about it is to measure, uh, the, the randomness, the diversity of brain activity. This is, I think what’s coming up here as sort of the way we did this in our lab. This is how to put a number on, on the complexity of, of brain activity. This would be something like maximally predictable. I mean you see this repeated pattern of, of ons and offs of blacks and whites.

ANIL SETH: In order to describe a pattern like that that’s so regular, you can do it very simply you just say on, off repeat until the end of time. And that’s, that’s a very simple thing. This is sort of maximally completely random now this is um, like white noise, snow on your TV when it’s not tuned to anything. This is actually the hardest thing to communicate, to transmit. There’s no predictable pattern at all. You have to, you know, to replicate this, you’ve got to replicate every, every point. And most of the, most patterns in nature and most patterns in things that we, we encounter, we’re somewhere in the middle. If we think about what your perception is right now, it’s a mixture of randomness and order and it’s capturing that balance between randomness and order that is quite difficult to measure but be, it’s also at this heart of this balance between explore and exploit.

ANIL SETH: You want to explore, you want to move the needle a little bit more towards randomness. You want to exploit, you want to move the needle a little bit more towards the structure that you already have in place. And so the idea is by using algorithms that actually, the same algorithms that would tell the difference between these three situations here, it’s actually the same algorithm that’s used when you compress an image in your camera and send it by email. We can, we can measure how under psychedelics you are increasing, you’re tipping the dial a little bit more towards diversity and that’s something that is distinctly measurable. I mean the other way to think about it is that under psychedelics also you tend to tip the balance a little bit more towards seeing patterns in things rather than just seeing things as they are. I mean, we can all see faces in clouds.

ANIL SETH: We all have a tendency to project our unconscious or conscious expectations or beliefs out there into the world. I like to think about perception as a kind of controlled hallucination. So all, all projecting things out and getting sensory data back in that refine and restrainer perceptions. And this needle too moves a little bit in psychedelics. This is actually uh, Sussex campus where I work and what we’ve done here is we’ve taken a kind of panoramic video of campus and we’ve used a machine learning algorithm, which is very good at detecting or classifying objects in scenes. It’s one of these so called deep convolutional neural networks. It’s very good. And what we do is we run it backwards. So we tell the network there are dogs and the network then updates the images. And so it’s not like just photoshopping dogs on I mean dogs are coming out of everywhere.

ANIL SETH: The whole thing is suffused by dogs so it’s not actually, there’s dogs in the sky that you know it’s a few too many dogs around there and it’s, I’m not saying this is equivalent to a psychedelic trip, but there are, you know, some people say there are certain similarities and the reason for doing this is A, it’s, it’s a lot of fun but we can use it for open days and things like this come to Sussex, you’ll have fun, but it gives us a way of getting, again, more details. So what might be going on within the brain that specifically leads to the sorts of phenomenology and that if to the extent that that is similar to a psychedelic experience we have, we have a hypothesis from there that what’s happening is again it’s, it’s moving the needle but this time the needle is moved towards, you’re more inclined, you seeing more patterns in things there’s more top down activity in the brain where your, your, your prior beliefs or expectations are overwhelming the sensory data so that you, your controlled hallucinations become a little bit less controlled.

EMILY SENAY: How do you actually measure that though in the brain?

ANIL SETH: Um, this is, this is the challenge. So for measuring just the randomness or diversity?

EMILY SENAY: Yes, randomness.

ANIL SETH: That we can do, we’ve seen that already. There are many ways we can try to measure whether the, there’s more kind of top down projection in the psychedelic brain. Um, this is an MEG scanner. This is where we get some of our data from. We don’t collect it at Sussex. I work with a group at Imperial College in London who collect the data at London Cardiff. Um, but it’s, it’s really it, the short answer is we don’t know yet. I mean we can, we can try to, we have to somehow fit computational models of brain dynamics that, that are doing something similar to that movie that I just showed you of Sussex and see whether those computational models also fit the psychedelic data quite well.

ANIL SETH: There’s an overlap here between what people are doing in what’s now called computational psychiatry. So for instance, in, eh, there’s often an association made and I don’t think it’s a particularly good association between psychedelics and psychosis. I mean, back in, in the beginning of this research, psychedelics were often called, were originally called psychomimetic drugs that they, they were simulating psychosis and, and maybe the extent to which they do is in this hallucinogenic property. And now in computational neuroscience we can build models of how psychotic hallucinations, uh, might be produced by the brain in terms of these expectations having a overly strong effect and we see they fit the data when we put people in brain imaging. And so trying to do that in the case of psychedelics would be, would be one way to approach that question. But we’re very much at the early stages of that.

EMILY SENAY: Very interesting. So we really have to talk about how psychedelics are becoming medicines, treatments for, um, a variety of conditions. Stephen, you’ve really, you’ve taken up the mantle here, you’re really on the cutting edge. Um, this has not been so easy to do, to pick up the thread of psychedelics that were dropped a number of years ago. What, how did you get into it? Uh, where are you now with this? Um, describe a little bit of the, the, the obstacles that you’ve faced when you wanted to explore this.

STEPHEN ROSS: Yeah, I got into this randomly. I didn’t know anything about it. It was like not part of my medical training at all. Zero. It wasn’t part of my psychiatry residency training and it wasn’t part of my, uh, addiction fellowship at NYU. The only thing I heard where some of the urban legends about it and all of the negative stuff. But, um, what I didn’t find out was that they were a huge part of psychiatry. And in 2006, a colleague of mine, just one day started talking to me about ayahuasca. I didn’t know what ayahuasca was, he told me that they were celebrating Albert Hoffman’s birthday, hundredth birthday, and why would anybody do that? And um, so he said no, Psychedelics were, you know, I think they are a big part of psychiatry and you, you didn’t have to look very hard, hidden in plain sight.

STEPHEN ROSS: I couldn’t believe that it was a huge part of psychiatry for about 25 years from the fifties and seventies. There were over 40,000 research participants and what really got me is the most studied indication with the best data was LSD treatment of alcoholism, and me being an addiction expert and alcohol being arguably the worst drug of them all from a public health perspective, that really captured my attention. And um, so, but I thought, well, so what, I mean that’s an interesting thing, but it turns out that psychedelics had restarted in the early nineties, Rick Straussman started it off. Even though Richard Nixon declared war on drugs and enacted the controlled substance act, there was always a route to do research with psychedelics and Rick Straussman got that going. And then Charlie Grove at UCLA and Roland Griffiths at Johns Hopkins, Francisco Marin at University of Arizona started like bringing it back. And Charlie Grove, I went to UCLA for medical school and he really encouraged me in 2006, you should do this and you should do an extension of our psilocybin advanced cancer trial.

EMILY SENAY: But meanwhile that wasn’t so easy practically. Is that fair to say?

STEPHEN ROSS: Well, you have to get what’s called a schedule one license. It took two full years to get the license. It was incredibly difficult. I’ve been working with the DA a long time as the head of our substance abuse division, but there were administrative hurdles. I didn’t think we would get very far. I thought leadership would say no way. But most of the leaders at NYU, um, kept allowing this to go on, except we hit a brick wall at Bellevue, my hospital that I totally love, where the head of the hospital said, we’re not, I’m not going to let you give psychedelics to dying African Americans in this hospital. He cited Tuskegee and just said, we’re not going to get in the media in a negative way. And so I was kind of heartbroken that my sort of beloved hospital did that. But then the NYU dental school reached out to us and I didn’t know we had a dental school at the time. Those dentists, I think that’s the only psychedelics study to ever take place in a dental college.

EMILY SENAY: Wow. Now you’re talking about psilocybin, but a lot of the original research that was mentioned in the introductory package used LSD, but so, so how do you use psilocybin today? What, what happened to LSD?

STEPHEN ROSS: Almost all of the research from the fifties and seventies was with LSD. Very, very little was with psilocybin, but in the modern era, when I looked at the data, I said, okay, we got to start with LSD and alcoholism. The data is incredibly robust there. There was a meta analysis in 2012 of 536 participants between five randomized control trials and it showed there was a clear treatment effect of single dose LSD, but LSD would have been a nonstarter. Those three letters are incredibly evocative. People think LSD, psychosis, jumping off of buildings, danger, bad chromosomal damage, and LSD for alcoholism would have created enormous cognitive dissonance. So there was a strategy to try psilocybin, which is a gentler drug. It didn’t have the political baggage and there was a further strategy to study advanced cancer and people who were dying and there had been an older, that was the second most studied indication after alcoholism so we decided to use psilocybin to treat end of life cancer distress.

EMILY SENAY: Okay. So that’s it. So, so it’s, it’s really a very specific population that it’s been studied in recently, not, not the older studies. And that is, describe what those patients are facing.

STEPHEN ROSS: In the modern era, by far the most studied indication is advanced cancer related psychological and existential distress. There have been three randomized controlled trials between UCLA, Johns Hopkins and NYU, it includes 92 participants. And between the three groups, what we found collectively is that single dose psilocybin produces rapid anti-anxiety and antidepressant effects that were a very large magnitude. In fact, after one day of getting single dose psilocybin, those in the psilocybin group, 80% no longer met criteria for cancer depression, and that endured at seven weeks and at the end, uh, at the end of the trial, eight months later. Compared to the placebo group where there, you know, it was a 20%, uh, had, were in remission. Um, and so we also found that, you know, single dose to last at least seven weeks, but possibly longer than that is, is a kind of breakthrough in psychiatry. We don’t have anything that works rapidly except ketamine. It degrades over a week. So to have something that can work so quickly and last so long, you know, could have enormous benefit. And in addition, we found psilocybin improved quality of life. It decreased existential distress. We measured cancer related demoralization and hopelessness.

EMILY SENAY: I think we have a graph that shows the, that really illustrates pretty well the difference that, that you’re talking about. Um, so tell us what this is.

STEPHEN ROSS: yeah, so, so you can see that the typical antidepressants, if you test antidepressants in the general population of people that have major depression, it’s actually now that a, the data from pharma that was suppressed has been published. It’s the 60% is lower. These are people that are responding, maybe more like 53 and the placebo is a little bit higher, maybe 45. So for severe depression, antidepressants tend to work, for other forms they don’t. Their medicines take a while to work, they have, they can have enormous side effects. Um, in cancer related depression the meta analysis show that the antidepressants don’t work any better than placebo. It’s about a 40%. So if our finding is real that one day after getting it 80% are in remission compared to 40%, if they responded several weeks, um, you know, it could have, um, you know, big implications in the treatment of people, you know, facing end of life distress who are depressed and anxious.

EMILY SENAY: We actually were able to interview two of the participants who were in that study on um, using psilocybin and I think we can take a look at that.

DINAH BAZER: I was diagnosed with ovarian cancer, stage 1C. My first thought was, now I know what I’m going to die of, which couldn’t have been true anyway. You still never know.

OCTAVIAN MIHAI: I felt a lump in my neck that came out positive for Hodgkin’s lymphoma.

DINAH BAZER: My life was just consumed by fear that this is coming back.

OCTAVIAN MIHAI: Things just really spun out of control.

DINAH BAZER: I was given the psilocybin.

OCTAVIAN MIHAI: I took the pill.

DINAH BAZER: I was in a space where nothing existed except me.

OCTAVIAN MIHAI: I became aware that this is probably what death would feel like. I’m still with my soul, but I’m not here anymore and it sort of gave me a lot of confidence because it really wasn’t that bad. It kind of gave me peace of mind because I had such a tremendous fear of this unknown that was death.

DINAH BAZER: I saw a large lump under my ribs and it was not the cancer. It was my fear. I just screamed (bleep) you, who the (bleep) do you think you are? Get Out. It was my real fear and it went away. I banished it.

OCTAVIAN MIHAI: I saw this black smoke come out of my body in like a mushroom cloud. I was thinking from now on, there is no more fear of death or cancer to terrorize me. I’m healed. I have everything to look forward to.

DINAH BAZER: And then I started to have very deep, deep feelings. The only way I could describe it, even though I’m an atheist and I still am, was just bathed in God’s love.

OCTAVIAN MIHAI: It was untainted. It was just pure happiness, pure harmony. It’s beautiful. I felt a different reality. It’s almost like hope.

EMILY SENAY: we actually have Octavian Mihai and Dinah Bazer here this evening, I think right up here in the front row, you’re both here? Octavian, where are you now? How are you doing? Thank you for coming and sharing your story.

OCTAVIAN MIHAI: Yeah. Thank you for having me. Uh, I’m doing great. Uh, my cancer is cured basically. It’s been over five years now. Yeah and I feel incredible. I mean, I haven’t had any more anxiety. Um, I’m just living life normally.

EMILY SENAY: And do you credit that with the, the drug?

OCTAVIAN MIHAI: Absolutely. I mean it, it basically all ended the moment the session ended.

EMILY SENAY: And it never came back?

OCTAVIAN MIHAI: No.

EMILY SENAY: Amazing. Really amazing. Dinah thank you for your explicit honesty in the piece. How are you doing?

DINAH BAZER: Um, I’m doing great. I have other anxieties. I mean, the state of the world is not really what I would wish for my grandchildren.

EMILY SENAY: Well, we’ve all got to work on that though.

DINAH BAZER: I’m not afraid of cancer. I have not been since that experience. It’s been nine years for me since I was diagnosed and treated. So I’ve been in remission all that time. And um, I was suffering such terrible fear and anxiety for the two years until I had the psilocybin. And I just, I just don’t think about it anymore. I don’t think about cancer. I don’t think about, I had ovarian, I don’t think about that coming back. I’ve had a few little episodes where I had genuine concern for my health and I went to the doctor and had it checked out and I was fine, and I didn’t freak out, you know, it was just, well, let’s just see what this is. So very, very different.

EMILY SENAY: Had, had you tried other therapies before this?

DINAH BAZER: I had not, except maybe eating a lot of candy.

EMILY SENAY: And you credit it as Octavian does with the single dose.

DINAH BAZER: Absolutely. Yes. Yeah.

EMILY SENAY: And what would you say to someone in your, in, in a position such as you, or who were, who was having the types of thoughts you were having?

DINAH BAZER: I wish that this drug were available therapeutically. Absolutely. And I know people that are in that situation now and I really feel for them and I wish they could have this.

OCTAVIAN MIHAI: Yeah, I agree with that. I actually, um, before I tried this, I actually tried Xanax, which was the typical thing. Someone, you know, the doctor was prescribed to me, uh, to kind of like help me with the anxiety and I have to say it really wasn’t working. Yeah. Except for those like six hours or so while it was in my system. After that, I would just wake up and it would all just be back to normal. So, um, yeah, that’s, that’s something I tried and that really didn’t work. So I really think that it would be important for this to, to become available because it’s pretty much, in my opinion, the only thing that’s actually getting to the cause of the problem.

EMILY SENAY: Thank you both so much. Really very interesting. So, so right now the most of the research currently being done that’s finished was in patients who had cancer. Is that correct? But we know that there are many other conditions such as, you know, PTSD, alcoholism, opioid abuse, um, and of course depression itself. And I think we have a graph here that shows, um, exactly how common it is. 300 million people globally. Uh, the World Health Organization says it’s a leading cause of disability worldwide and just here in the US it costs $210 billion annually. So when we’re talking about rolling out these drugs and looking at these different, um, conditions, if you can, for depression, where are we with using these drugs in depression, on not just in depression related to cancer and opioids and alcoholism and PTSD, so on and so forth. Can you break that down?

STEPHEN ROSS: Yeah, there’s a big push now to develop psilocybin to treat major depression. It’s uh, 10% of the US population. It’s one of the biggest causes of global disability. And, um, the, the data from the cancer work was taken up by several companies. One is the Usona Institute, the other is Compass and they’ve gone to regulatory agencies. In fact, the FDA has granted compass breakthrough status to study psilocybin and treatment resistant depression. The only data was a small trial done at Imperial College by Robin Carhart-Harris that didn’t have a control group. So the data on depression’s very small, it potentially is very promising in that area and we’re about to be involved in a multicenter trial using psilocybin to treat major depression. And um, I think that it’s a great idea to sort of go in that direction. What I like about psychedelics is that they are being tried on very difficult to treat disorders that do not have good treatments and of life existential distress.

STEPHEN ROSS: There is zero pharmacologic treatments for that. The treatments for depression tend to not work that well. They have lots of side effects. Addiction is in the other areas I mentioned. Um, the most studied indication was alcoholism with the LSD. In the modern era, um, that’s been taken up by our group at NYU, uh, is doing a trial that by Michael Bogenschutz using psilocybin assisted therapy to treat alcoholism. We’re almost done with, with that trial another, uh, 20 participants to go. And we’d done it about a year. Matt Johnson’s leading a trial at Johns Hopkins using psilocybin to treat tobacco addiction. That trial, it’s also nearing the end. There’s a trial at the University of Alabama lit by Peter Hendricks studying psilocybin to treat essentially crack cocaine addiction in African American individuals. And there’s promising data there. There’s a trial at the University of Madison, Wisconsin that just started, about to start using psilocybin treat opiate addiction. And our lab is also moving in the direction of opiate addiction as we have this horrible crisis. So there’s so many different directions to go and it keeps opening up. Hopkins a has designed a trial using psilocybin to treat anorexia, the most fatal psychiatric condition with no medications. So it’s, there’s so many different directions to go therapeutically. Um.

EMILY SENAY: So we’re at the beginning. Would you say?

STEPHEN ROSS: We’re at the beginning, but I predict over the next five years, psychiatry will be radically transformed because I think I would predict in three to five years MDMA will be rescheduled and made available for PTSD. And I think psilocybin soon after that, so in five years, um, you know, practitioners will be able to use ketamine, MDMA and psilocybin in highly regulated settings for very difficult to treat disorders and I think that will radically change psychiatry.

EMILY SENAY: Well, I want to come back to deliver a few key caveats on, on what we’re talking about, but Eduardo I want to ask you a question. You have seen this in a very different setting. Does it surprise you at all that, that psychedelics are now sort of, uh, possibly becoming key treatments for some of the major illnesses that were, we have.

EDUARDO KOHN: No, it doesn’t, it doesn’t surprise me at all. I mean, I think psychedelics, one can see the potential of them even in, in traditional settings. Um, you can also see that, um, that, you know, I think there, there are lots of things that are interesting that are happening here. One, there is a, uh, a fascination with psychedelics, right? Um, there’s of course the hard scientific interest in them because of all the reasons you’ve laid out, but we’re also sort of fascinated by this thing and I think that that fascination with psychedelics, although in many ways positive is also, is also a symptom of something. It’s a symptom of a kind of disconnection that we feel and I don’t necessarily feel that taking psychedelics is the cure to it. Something else. It’s finding other ways to be connected. So I see, I see, uh, possibilities and risks at the same time.

EMILY SENAY: Um, Denver recently decriminalized magic mushrooms, there is a trend, uh, to so called micro-dosing, apparently popular in Silicon Valley and on Wall Street, uh, where I guess, do they call them yuppies still? I don’t know. Um, um, use this to sort of get ahead, get an advantage. They’re more creative but, but I think I need to ask each of you there. This is first of all, what are the risks involved in psychedelics and how really should they be used? Um, should people freelance on this stuff now? What’s your, what’s your take on it? Eduardo, I want to start with you.

EDUARDO KOHN: Well, I, I’d like to go back to that video that we saw at the very beginning. In some ways the reason why psychedelics are so threatening to society. In some ways is a positive thing. Um, they do, they can disrupt the order and there is something wrong with the order today. It’s interesting that the Amazon, um, is a, is an area politically that has never been fully under the state. And it’s interesting that Amazonians are coming up with solutions for problems that in some ways are created, have been created by states, uh, the environmental crisis, the climate change. So there’s something interesting, uh, disruptive about psychedelics, which I think we have to in some ways accept even though it is a dangerous game. Um, but I think there are other, there are many dangerous, I mean there’s a, there’s a real problem with, uh, in the Amazon of ayahuasca tourism, this fascination with this leading people to go into the Amazon disrupting traditional-

EMILY SENAY: Meaning people traveling there. What, what is that exactly?

EDUARDO KOHN: Ayahuasca tourism is a, is a phenomenon. It’s very strong. It’s much stronger in Peru than it is in Ecuador with a lot of people searching for, feeling that this is the solution to their problems and bringing lots of problems to those areas because of that. Now of course, um, Amazonian folks who deal traditionally with the ceremonial use of these plants are not stingy about this. There are moments and places where it’s important for them that other people can be open to this, but it has to be done on their terms. And, uh, this is not, um, something that can be done that’s sort of at a mass scale.

EMILY SENAY: Yeah. I find that the tourism really interesting, Alison, thoughts on, on, um, how they should be used, how we should look at it. And also some of your caveats regarding what it means to have a child like mind and obviously separating out that none of this is being used in children at all. Um, explain, explain the difference there that we’re talking about.

ALISON GOPNIK: Yeah, so I think, I think a theme that comes up again and again is that, um, I mean there are some specific dangers. People who are prone to psychosis for instance, can have very negative experiences. Um, um, so it is extremely important that people be screened beforehand. Um, I think both in the kinds of settings that Eduardo was talking about and in the kind of settings that Stephen is talking about, the preparation beforehand and the integration afterwards and the fact that this is happening in a controlled kind of way is, is absolutely crucial for, uh, for it to, to have positive effects rather than negative effects, rather than to have risks. But also I think that the, the point is of the point of opening up these possibilities is then to do the adult work of actually implementing something that’s different. Of actually changing and having possibility as we know.

ALISON GOPNIK: I mean, children are wonderful because they’re open to possibilities, but they can have experiences that shape them in wonderful ways and they can have experiences that shape them in, in terrible ways too, um, and I think that’s true as well for adults in these circumstances. So figuring out what the right kind of cultural tradition, and part of the trouble is, we don’t have good cultural traditions for, for dealing with, uh, for dealing with these substances or for dealing with these experiences in general. And I think there’s some anxiety that what happened in the 60s could happen again because we don’t have the right kinds of contexts and traditions to, to, to make these things happen. And the kind of therapeutic uses that Stephen is talking about are a really good model for very careful and controlled kinds of, uh, kinds of uses of the substances.

EMILY SENAY: Uh, Stephen, I’ll ask you, there are some contraindications. Um, if people are listening to what we’re talking about tonight, tell us what some of those are regarding other medications they might be taking.

STEPHEN ROSS: Yeah, psychedelics are definitely not for everyone. They’re not miracle magic drugs that should be used by everybody. Um, they have real risks. There are some medical risks. So psilocybin is remarkably safe from a physiologic perspective, um, although it can mildly increased blood pressures. So we really, we rule out people with hypertension or you know, history of serious heart problems. Um, the main problem, the adverse effects are in the psychological realm. Uh, as Alison was saying, these are not drugs that people with psychosis should be taking. They can exacerbate psychosis or occasion the first onset of psychosis in a teenager that were to use it. So, uh, we rule those people out. They’re not for people that are psychologically unstable. Um, and so you really-

EMILY SENAY: Other medications?

STEPHEN ROSS: There can be medication interactions. I mean, so for instance, I don’t think many people know about this. All these people going to use ayahuasca who are on antidepressants, um, antidepressants, serotonergic antidepressants and ayahuasca can interact to cause a condition called Serotonin Syndrome because there’s an MAO inhibitor. And so I, I worry that if people get the idea that psychedelics, they can use them even if they’re trying to use them medicinally. Um, outside of a kind of structured therapeutic setting, I think bad things can happen and I, and I agree that history could repeat itself. This could go from miracle drug to demonic drug and I think we have to look to the history of all this so that we’re careful to not repeat the same mistakes.

EMILY SENAY: Anil?

ANIL SETH: I think the thing that’s coming out is freelancing is probably not the best way to approach, uh, the renewed interest in psychedelics. I mean if I, if I think on the, on the positive side if I project a few years out into the future, I really can see both in the basic science sense that research with psychedelics becomes a core part of our attempts to understand perception, consciousness and self in general, part of the toolbox that one of the most important parts of the toolbox that we can use to systematically manipulate, uh, conscious experiences and then study the neurobiological basis of that. And then in the clinical realm too, I mean I just to echo something that Stephen said, typically if you’re trying to find a pharmacological treatment for something, there are three criteria that you think about. Is it toxic, is it going to kill you? Is it addictive?

ANIL SETH: Does it affect the system in question? You want the answer to the first two questions to be no and the third question to be yes, and the psychedelics ticks all those boxes. Plus there seem to be plausible mechanistic reasons why it might have an effect. So for something like depression was mentioned, depression can be characterize to some extent as repetitive ruminative thinking. So the idea that you can open up new ways of thinking, break the ruts, shake the snow globe. That’s at least a plausible starting point. It’s of course not a fully fledged theory of the psychopharmacology of depression, but it’s a starting point. And the fact that maybe you only need one trial rather than loads. I mean that’s another great point. Of course, this is also why the pharmaceutical industry has been less, maybe not so keen. We can’t make many money out of it for Christ’s sake.

ANIL SETH: You want a drug that costs a lot, that people take every day. That’s not the psychedelic way. So I think there’s a lot of positives, but uh, as well as the pharmacological interactions, I think, I just want to echo this thing about ayahuasca and SSRIs, uh, it’s, it’s really important that, that those do interact but set and setting is, is critical. And so yeah, the back to where we started, the signature effect of psychedelics is that the malleable way with which they affect our experiences of the world and the self. You can take an antibiotic, it doesn’t matter what you take, it’s going to have the same effect on your system. Maybe much the same for some other psychoactive drugs, but the effects of psychedelics depends so much on the context you’re in. Which is why we have the, the shamans in the Amazon. Why we have the white coat shamans in the psychedelic trials of Stephen, to be guided through these experiences in a way that allows you to integrate them later on after the event. That’s where the risks, that’s where the caveats are. That’s why freelancing is not so good but done the right way. I, I’m really excited about, uh, where we might be in a few years time.

EMILY SENAY: Give me, give me your, your picture of a few years from now. Where do you think this is going?

ANIL SETH: In the neuroscience I think we’ll have connected the dots a lot more as Alison said we’re at the beginning. We know the pharmacology and we know to phenomenology and some of the large scale stuff we would be able to answer one of the questions you asked me earlier about for instance, how is it, why is it that the psychedelics have the specific effects they do on, on phenomenology, on the dissolution of the ego, on seeing patterns in clouds or, or, or, or, or seeing life where we don’t experience in the connectedness of all things. We’ll be able to connect those dots much more, much more, um, strongly. And I do think that barring some disaster barring some overreach, which causes the whole thing to be shut down again, there are increasing numbers of groups, uh, having, getting licenses to try well-controlled clinical interventions and I see that becoming much more embedded, much more widely available. I think that the application to depression, uh, will become a big, a big focus and I’m pretty positive.

EMILY SENAY: You had a message to deliver from the, from your travels. Can you repeat that message and tell me where you think things are going to be in the next few years?

EDUARDO KOHN: The call from the Amazon is to live psychedelically, which does not necessarily mean taking psychedelic drugs. It means living in full recognition that what life is about is to be in a state of emergent mind, connecting with the emergent mind that holds us and to learn that that’s where, that’s where that life force comes from. That’s the message that they’re wanting to transmit.

EMILY SENAY: Alison, project into the near future where, where do you see this going?

ALISON GOPNIK: Well, I think as Anil said it holds tremendous promise for actually understanding things that have been challenging forever in cognitive science. Like a understanding how consciousness works. Understanding this very basic question of how our experience is connected to what’s going on in our minds, in our brains, understanding the sort of computers that are inside of our skulls. But I also think that there’s at least potential for both clinical changes and perhaps for changes in our attitudes towards things like our relationship to nature. Which seem like particularly important attitudes to change at this particular, at this particular point in our history. And I should, I should maybe add, we have the great hope that we have new generations of children, new grandchildren who are, who are showing up, who just independently will give us the possibility of making those connections and making those kinds of changes. And I think you can already see that. You can already see that happening.

EMILY SENAY: Stephen, are we going to be writing prescriptions for these in the next five years? Are we going to see a major revolution in, um, treatment of mental illness with the psychedelics?

STEPHEN ROSS: I think so. I, I, we need to do more research. We need to replicate these findings. They’re almost too good to be true. And so we have to do, you know, really good science and then follow the data to find the truth. But my prediction is that the terminal cancer work will put psilocybin over the line within the next five years, the FDA is incredibly open to all of this. And, um, I think depression and addiction in parallel also gonna get, get close. Um, if it’s rescheduled, you’re not gonna be able to go to CVS and get it, they’re gonna be mandated through the FDA, through the REMS program that can only be used in licensed clinics by licensed therapists. We, I created a NYU psychedelic psychotherapy training program about a decade ago because it’s such a unique form of training. I think people will have to, you know, go through those. And, um, but I think it will dramatically transform psychiatry. I think it will transform the care of dying people who have this demoralization, existential distress that have nothing and die in a sort of pain and a horrible death that, that, that’s my biggest hope for it. Um, in terms of the, the cancer work that we’ve done, but I, I’m very hopeful to transform the care of addiction as well.

EMILY SENAY: Terrific. I want to thank Eduardo, uh, Alison and Anil and Stephen for this discussion this evening. Thank you all for coming.