Instant Genius - How psychedelics could kickstart the next mental health revolution

Episode Date: October 23, 2025

Hippies, the Beatles, flower power, magic mushrooms, raves and festivals – that’s what most of us associate with psychedelics. But there is mounting evidence that these drugs could also be used medicinally, particularly to treat mental illnesses such as depression. In this episode, we speak to Prof David Nutt, a psychopharmacologist who has spent decades researching how drugs affect the brain. Now a professor at Imperial College London, David has published more than 500 research papers, eight government reports, and 40 books – including one called Psychedelics, in 2023. In this conversation, he explains how psychedelics affect the brain, how they alter people’s sense of self and perception of reality, and why they could revolutionise the future of mental health treatments. Please note that psychedelics are Class A drugs according to UK law. Anyone caught in possession of such substances can face up to seven years in prison, an unlimited fine, or both. Information and support for those affected by substance abuse can be found at bbc.co.uk/actionline. The following conversation specifically concerns psychedelics when used in a clinical context, given at low doses and under medical supervision. Please don’t try this at home. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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That's what most of us associate with psychedelics. But there is mounting evidence that these drugs could also be used medicinally, particularly to treat mental illnesses such as depression. In this episode, we speak to Professor David Nutt, a psychopharmacologist who has spent decades researching how drugs affect the brain. Now a professor at Imperial College London, David has published more than 500 research papers, eight government reports and 40 books, including one called psychedelics in 20. In this conversation, he explains how psychedelics affect the brain, how they alter people's sense of self and perception of reality, and why they could revolutionise the future of mental health treatments.

Please note that psychedelics are class A drugs according to the UK law. Anyone caught in possession of such substances can face up to seven years in prison, an unlimited fine or both. Information and support for those affected by substance abuse can be found at BBC.co.uk forward slash action line. The following conversation specifically concerns psychedelics when used in a clinical context, given at low doses and under medical supervision. Please don't try this at home. David, thank you so much for joining me on the podcast. Welcome.

Oh, it's good to be here, thank you. So we're going to be talking about psychedelics today. It's something you know a lot about and you've written a book about. What are psychedelics? Well, in simple terms, psychedelics are a group of medicines, drugs, most of which were found in nature, or have been found in nature, which are used to produce profound alterations in consciousness. And they've been used for thousands of years to allow people to get different ways of thinking, to help transition from adolescence, so adulthood. to facilitate healing activities, often in a group setting, particularly in relation to ayahuasca.

So they're essentially drugs which profoundly change the brain. And I suppose the key thing is that they allow people to think differently. And in fact, the term psychedelic is a word made in recent times, but it's from two Greek words. It means mind revealing. and a lot of people who take psychedelics and get a sense in which their mind is now working differently and sort of free from the, I suppose, the habits and misconceptions that they had until they took them. So you mentioned ayahuasca there. What are some of the other main psychedelics that people tend to talk about?

So of course, the sort of one that most people know about is LSD, lysergic acid ethylamide. And that was a derivative of earlier psychedelics that were used back in ancient Greek times, which were essentially lysurgic acid derivatives. But LSD is an extremely potent variant of those, which was actually made to facilitate blood flow to the brain, but turned out to have much more powerful and possibly important effects in that. And then there's cylusybin, which is magic mushroom juice, which has been around since way before humans. And in fact, the earliest recorded image we have of a psychedelic experience is the Algerian mushroom man, which was painted on the wall of a cave in Algeria about over 7,000 years ago. And it's a man made up completely of mushrooms. And they look like magic mushrooms.

And we presume no one would have bothered to paint a man of a mushroom man if they hadn't taken the mushrooms. And then there are what you might call the sort of pure extracts of some of these plant or fungal products. So ayahuasca, we mentioned, is actually a very clever cocktail of two plants. The active ingredient is a psychedelic called DMT, dimethyltryptamine. But if you take that orally, it gets broken down by the liver, so you don't get in effect. But the indigenous peoples of the Amazon discover that if you brood it up with another plant, then it would work. You can have a drink, a psychedelic drink called ayahuasca. And it turns out the other plant contains a substance called harmaline, which prevents the breakdown of DMT.

Now, in the Western science, we tend to have to use the pure molecule, so the synthetic DMT. And therefore, we can't give it orally. We have to give it either intravenously or you can smoke it if you want. And then there's also another more recently understood and talked about psychedelic called 5MEODMT, 5 methoxy DMT, 5 methoxy DEMT. And that's often known as the toad because there's a particular toad, the Sonora Desert Toad, which secretes 5MEO through its skin. We don't know why, but I suspect it's to deter predators because it probably produces quite a profound state of alter consciousness in the foxes or the snakes who try to eat the toad. And then there's, of course, there's the quite famous one called mescaline, which is part of, which is where mostly originates in cacti. And it's used, it's the active ingredient in the peyote cactus, which is used in the North American indigenous rituals.

And there's also cacti in South America, which also produced mescaline. And that's been used for thousands of years as a way of helping people cope, particularly with the problems of living. at high altitude in the Andes where life is pretty miserable, but psychedelics seem to give you a bit of resilience and maybe give you something you couldn't get from other parts of that environment. Interesting. I think also in your book you wrote about MDMA and ketamine. To what extent are these psychedelics? So ketamine and MDMA are powerfully psychoactive and they're also being used therapeutically in similar ways to have. psychedelics are being used. But they're not true psychedelics, and that's because they have a different pharmacology. And also they produce slightly different mental experiences. So the nearest to classical psychedelics, the ones I've described already, is ketamine. Now, ketamine also produces similar,

not identical experiences. People can tell them apart. But when we do measurements of the brain, ketamine does produce very similar change in function of the brain as classic psychosophobic. psychedelics, and that's a state we call increased entropy. The brain becomes more flexible, more connected, and that connectivity is one of the reasons why the experience, the psychedelic experience exists, and also why it's therapeutic. So although ketamine produces a similar brain signature to psychedelics, it does it through a different mechanism. Ketamine actually was an anaesthetic, and it was used for anaesthesia for about 30 years before. it began to be used for other forms of therapy, particularly the treatment of depression.

And what ketamine does is to block a receptor in the brain called the NMDA receptor, which actually was a receptor that was kind of discovered in Bristol. And the first drugs to work on that receptor, to define it, were actually discovered by Jeff Watkins at Bristol University many years ago. So what ketamine does is block this receptor. And that receptor is critical for consciousness. If you block it, then you become unconscious, and that's what ketamine does as an anesthetic. But if you take a lower dose, then you change consciousness without blunting it completely.

And that altered consciousness is what we use when we're using ketamine therapeutically. MDMA is a very different molecule, because what MDMA does is to release neurotransmitters. And the one it releases particularly is serotonin. But the predominant effect of MDMA is to dampen down the fear centres in the brain and reduce fear. And that is why it's used therapeutically to help people overcome fear or trauma disorders like PTSD. So why are you personally and professionally so interested in psychedelics? Well, I'm a psychiatrist. I've been practicing for pretty much 50 years.

I think I've wrote my first prescription in 1972, so that's over 50 years ago. And I spent most of my life researching new ways of helping people with mental health problems. And we haven't made much progress. The last 20 years, it's been very barren. It turns out it's very difficult to innovate new brain medicines, partly because we don't understand how the brain works, partly because it's very costly to develop them. It can cost over a billion pounds to develop a brain medicine. So it's proved to be very difficult to innovate new psychiatric medicines.

And that has led to most companies pulling out. The investors don't want to spend a billion dollars on an innovation, which might not work. And companies have moved into areas like cancer therapy where the time from discovery to market is much shorter, maybe six years instead of 13 years, and the costs about a quarter to a third. And that's left a deficit, dearth of innovation. And psychedelics turn out to have real potential in filling that gap. Because to our surprise, and I think to many people's surprise,

they actually do have powerful therapeutic effects. They're not just something that makes you feel different, think differently. They're not just about giving you insight. They're actually about helping people heal. And that discovery is one that we actually started off making in Bristol, where we began this research over 20 years ago. And it's worth noting that our expectation was not to find a therapy. The reason we began this research was who actually asked the question,

what are these receptors doing? where does a human brain have so many of these receptors the psychedelics work on? In the parts of the brain, we actually define what humans are. And no one to that point has actually studied these drugs using modern imaging techniques. Why? Because it was difficult, largely because the drugs were illegal, and it took years to get permissions. And quite often it was impossible to get funding.

So we began the research to ask the question, what is the psychedelic state? And it turned out the psychedelic state was not only a very interesting state in terms of the brain images. They explain the psychedelic state and we can talk more about that later if you like. But also some of the changes

that particularly silocybin produced in the brain, the first studies we did were with psilocybin, those changes were similar to the ones produced by many different treatments of depression. The only difference is that they, kind of work fast, you know, within half an hour or so, whereas many treatments take weeks or months to work. And it was those what looked like signatures of an antidepressant effect that led us to go on and do the trials to see if psilocybin would lift depression, and lo and behold,

it did. And it also did it fast, rather than that conventional antidepressants, which should take six, eight weeks to work. Let's talk about then how the psychedelics seem to affect the brain. What did you find when you started imaging the brains of people taking these drugs? Well, the first thing we found was something we absolutely had not expected. Because we had assumed that the powerful experience of altered consciousness, of your altered vision, synesthesia, strange sort of mystical experiences, we assumed that that powerful change in the brain would be manifest by a, an increase in brain activity, and it wasn't. In fact, what we found, and it was quite difficult

to get this published, we found exactly the opposite. We found that psilocybin dampened down certain nodes and circuits in the brain. In fact, we were so surprised by that. We thought, have we done it wrong. So we repeated the whole study using a different sort of analysis of the brain images and came to the same conclusion. And then we had to rethink, okay, so these drugs don't turn on the brain, like Timothy Leary said, they actually turn off the brain. But it turns out that they turn off the brain nodes and circuits, which are critical for driving depressive thinking, which is why we then moved in to use them in depression

and discovered not only that they worked, but also that they change the depressed brain in a direction where it's much easier not to think depressive thoughts. They make the brain more flexible in the long term. So during the trip, the brain is very flexible. That is what a trip is in many ways. But afterwards, you can see that this increased flexibility lasts for weeks and weeks.

And people, our patients and also healthy volunteers, describe an ability to think differently, to feel more connected with themselves, with other people, with nature, with the world, with God, if they're religious, and more able to resist the drag that the brain puts on them to suck them back into the depressive thinking they had before. So it's a kind of reset to the brain, puts it back in a way to where it was before they were depressed. So let's get stuck in then to the specifics. Like what, when you say that it kind of turns off the brain, what does that actually mean neuroscientifically? So we were using fMRI techniques. And there were two measures we use. One was brain blood flow and then the other

was brain oxygen oxygen. Or so-called the bold technique, brain oxygen level dependence. And they both are measures of brain activity. Because when your brain is more active, you get more blood flow, obviously to get oxygen to the active neurons, and you can measure that in these two different ways. And both of those measures showed that a circuit in the brain, we call the default mode network, the activity was reduced by the psychedelic. Now, that was completely paradoxical because we knew from other preclinical work, if you record from their electrodes deep into the cortex, that psychedelics increased the firing of those neurons. But overall, the net effect is to switch off a circuit.

And that is probably through enhancing the release of GABA, which is the inhibitory neurotransmitter. But that switching off is interesting because it occurs in the network, which is the network in which humans do their thinking about themselves. So when depressed people are thinking, I'm a worthless person, I've let someone, people down, I don't deserve to live, when they're having those repetitive, what we call ruminations, the default mode network is overactive. And that's one of the reasons why depressed people struggle to do other tasks. So it's very classical that the press person

struggles to read a newspaper or watch a film for more than a few minutes because they cannot detach themselves from those inner, that inner monologue of worthlessness and self-criticism. and by switching off the network in which that monologue occurs, they can escape from depression. So it turns out that the default mode network is actually not just involved in depression. The default mode network is the network in which you, as a human being, with a sense of self and autonomy, conducts its business. It's where your ego is, if you're a Freudian, if you're a religious person, it's where your soul would be. seated. It's where you as a person really do or your personal thinking. By switching off the

default mode network, psychedelics allow the brain to work differently. It becomes more connected. And the analogy I like to use is that the default mode network is like the conductor of an orchestra. And if you switch it off, then the individual musicians can play what they want. So instead of playing Bark, they might play jazz. In that way, you think differently. If you've never been allowed to play anything other than Bark, well, then you can't play anything other than Bach. But if you're allowed to play, to experiment,

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So we've talked about kind of this flexibility. What about connectivity then? In the psychedelic state, there is increased connectivity. Parts of the brain which have not connected to each other since you were probably a child, now become connected. And in a way, what psychedelics do is that you put your brain back to that sort of innocent period before you would engage. in the education developmental processes which make you what you are. And one of the theories we now have is that education is a process by which, or maybe learning is a better, in a more global term,

learning is the process by which your brain gradually acquires a whole series of skills, which are actually very similar to the skills of other people. So, I mean, the example, of course, is language. It's really important if you're using words You use the words in the same way as other people In fact, once you've learned a word It's almost impossible to unlearn it If you think a word means this

It always means this Because your brain is a learning machine And it really makes it very deeply ingrained The content of the meaning of something But the problem is Suppose you learn the wrong thing Suppose there's a child you know, if you're a child and you're mistreated, but you believe it's your fault because children,

when they're very young, have a sense that they are the center of the universe, that they do have autonomy. In fact, they kind of believe that people work to their call. You cry and the mother comes, but if something bad happens, then you tend to think it's your fault as well. So if you deeply ingrain a thought that you're a bad person, because you're told you're a bad person, say, by your mother or your father, it can be really difficult. to un-ingrain a thought. And that then perpetuates into this depressive ideation as people get older. And psychedelics are the only treatments we know that can actually put the brain back to a state where it was before it was deeply ingrained, at least with emotional thinking. It doesn't stop you

remembering the name of words. You might use them differently in a trip. But it doesn't disrupt the sort of hard-wired, what we call declarative memory. But it definitely allows people to escape from hard, deeply entrenched, probably hardwired emotional memories. Okay, super interesting. What about hallucinations? Because I think often when people think about psychedelics, that's the first thing that comes to mind that psychedelics are known for these hallucinations

that you not only think in a different way, but you see the world differently. Why do hallucinations happen? So to understand what is going on in the brain and in terms of, say, visual hallucinations or with psychedelics, You have to understand how the brain creates an image. And your brain is not a camera.

If your brain was a camera, it would have filled up its memory banks before you were old enough to say camera. Your brain is a very sophisticated device for making inferences about the world. So the process of seeing is essentially taking electrical, impulses which are generated in the eye by light, sending them to a large chunk of the back of the brain, maybe a quarter of the brain is involved in orchestrating the reconstruction of those electrical impulses into a vision.

Now, under psychedelics, the neurons which do the reconstruction are pulling together data from all many, probably billions of neurons across the visual system. they're integrating inputs and creating a whole. We call that a percept. Psychedelics disrupt that ability to integrate and produce the same analysis, the same percept as before. And in fact, what you see as a hallucination under a psychedelic

is exactly what people predicted when they did the very early experiments of how the visual system reconstructs vision from electrical impulses. Ubel Invisal got the Nobel Prize for working out that the basically the neurons of the visual system start off by creating simple shapes.

They create edges, they create circles, they create colors, and they create simple movement. Under psychedelics, that is what you are seeing. You are seeing the primary processing of your visual system, which you've never seen before, except when you were a baby. before your visual system learned how to do all the processing.

So you eventually came to see a chair, but what it is, a chair, every time you saw a chair. So I think that's one of the most sort of thrilling accidental outcomes of this research, because we've kind of proved human and weasel right. The human brain does reconstruct images in the same way as other brains, and that's disrupted by psychedelics. What are some of the side effects or dangers? when people take psychedelics, all the things that people should be wary of. Yeah, so there's a powerful, powerful drugs.

And, you know, you should never take them alone. You should never take them anywhere where there is any risk of you doing something silly, like on the edge of a cliff or in a lake or something. There should always be someone with you who is not taking these drugs in case you get into difficulties. ideally you'd know what you were taking as well and the amounts you were taking and you would always start with a low dose just to make sure that what you were given wasn't accidentally stronger than you anticipated. The biggest negative is if you have anxiety during a trip, that's often called a bad trip. And anxiety before the trip often does lead to a bad trip.

So one of the things we try very much to do, particularly with our patients, is to. to reduce anxiety to prepare them so that they can maximize the benefits in the experience of a trip. I want to just say one important thing here. For most of our patients, the trip is not pleasant. Because for most of them,

they are going places where they've probably been actively avoiding going for a long time. One of the theories of depression is that people think a lot about themselves to avoid thinking about the persons or people or accidents and incidents in their lives which have traumatised them. Though it's a defence against reliving trauma, that defence is broken down during the trip.

So people will go back to the trauma. And that's the key reason why they can overcome the trauma because for the first time, maybe in decades, they can actually remember what the trauma was or at least access it and deal with it. So we don't call those bad trips. We call it challenging, but they're not bad because it's what you have to do.

It would be like saying, well, surgery for a knee replacement failed if you had pain. Well, obviously you're going to have pain if you chuck a bone off. Obviously, if you're reliving trauma, you're going to have psychological distress. So we're very clear that there is an emotional challenge

for people with mental illness, which they have to overcome and psychedelic didn't happen to do that. But people who use them recreationally can have bad trips, and those can lead to them, never wanting to take them again, which is perfectly fine.

Some people do get enduring anxiety afterwards. Some people feel worried that they've somehow damaged their brain, although there is no evidence that that happens. But some people do get what's called HPPD, a hallucin persisting perceptual disorder. And that's most characteristically sort of some flickering lights at the edge of your vision. Sometimes they have colours as well. People with that often think they've damaged their vision.

Again, they haven't. There's some change in the interpretation of visual inputs, which gives you this side effect. it rarely is problematic. They still live for real normal lives. Most of the issue comes from being anxious about having harmed themselves rather than actually harming themselves. So we all know that lots of drugs are addictive,

but how addictive are psychedelics? It's important to know that psychedelics, the serogenergic psychedelics, are not addictive. They are not addictive. If you take them more than three days in a row, the effect disappears. We have known that since the 1950s. When the CIA did studies to work out how to protect soldiers from psychedelics,

and they worked out if you gave the soldiers psychedelics for a few days, then if the Russians poured LSD out of the skies, the soldiers wouldn't be affected. So we know they're not addictive. In fact, there were six trials in the 1960s of LSD for alcoholism, a single dose of LSD produced outcomes, which are three times better than any modern treatment for alcoholism. but we've not been allowed to use it because it's an equal. And just on a bit of hope here,

we have just got funding from the NHS research arm to do the first trial of psychedelics in people who use heroin, who have been detoxified from heroin, and we're starting that trial to see if we can help people stay abstinent from heroin for longer than the few weeks, which is the current best outcome. There's also been a major study in the States replicating that psilocybin,

two doses of psilocybin can have profound benefits in treating alcohol dependence in the same way as LSD was shown back in the 1960. So we're very hopeful that for addiction, psychedelics may also be a breakthrough. And they have a particular potential in gambling because there are no drug treatments for gambling. It's not a drug,

so you can't block the effects of the drug. But psychedelics, we think, might disrupt the circuits that underpin addiction to gambling and help there. Okay, interesting. And you mentioned anxiety there, and we've talked already a lot about depression. What are some of the other mental illnesses that can or can't be affected by psychedelics? This is a field that's growing very rapidly. So having started and done now two major studies, depression, we began to think what disorders might these brain changes facilitate healing from. And we came to the conclusion there might well be disorders in which either there's enduring trauma like PTSD or their enduring thought patterns which the patient knows are wrong

but which they can't change. And that led us to do, I think, two major studies. the most important one so far. One is in a condition called OCD, obsessive compulsive disorder. People with OCD often have repetitive thoughts which they know are wrong and they often have thoughts which lead them to engage in repetitive behavior

which they know is pointless. But they can't stop. So someone with OCD knows they don't have to wash their hands 30 times to get rid of germs. But they can't stop. stop doing it. And we showed, and this was a very interesting study because it was not a psychedelic dose, it was a lower dose, what we call a psycholytic dose, a dose that made their

brain more flexible without hallucinations. We found that dose could give some benefit for a couple of weeks in people with OCD, a benefit equivalent to being on, say, an SSRI, which is the kind of treatment for several months. And now we're trying to raise funding to do that repeatedly, to see if we can carry on and get bigger and bigger effects if we use it, say, over six times rather than just once. And then the other disorder is anorexia nervosa. People with anorexia nova have a sense that they are too fat and the eating will be very damaging to them.

I mean, they know that's wrong. They know they're not too fat, but somehow they've got entrenched perspective on their body. And they have a habit, which is basically self-starvation. And again, we found that two trips could profoundly change. About a third, we had 20 women, female patients, about a third of them after the second trip. And this effect persisted for up to six months had quite a different perspective on their desire to be thin. They could see, and this is important, I think, they could see that during the trip.

they could think differently. Some would often say, I could see myself. I was outside myself, and I could see myself as someone defined by anorexia. But I am not that person. There is another side to me. And so we're very excited by that because I think this could be a really important breakthrough because anorexia has a very, very difficult disorder to treat. And it's got mortality rate equivalent to that of depression,

about 15% of people with anorexia. erexia nervosa will die as a result of the disorder over their lifetime. So what do you hope for the future of psychedelics? Well, my great hope is that people embrace the fact that these are a breakthrough. This is the biggest breakthrough in psychiatric treatments, certainly since the 1950s, when we accidentally discovered drugs like antidepressants and drugs for psychosis, antipsychotics. And we haven't really done more than just modify those in the last 50 years. and we need to do better.

We know that the cost of mentally illness are vast. We know that there are 5,000 people in Britain this year will commit suicide. Over a million people globally will commit suicide. And most of those have got a mental illness. And most of them, at least in the Western world, have been in treatments and the treatments haven't worked. So we do to do it differently.

Psychedelics, we know work where I, other treatments haven't worked. We've done a study on that. The anorexia study shows that. The OCD study shows that. The depression study shows that. And they do that because they work in a different part of the brain. So you do have hope. If conventional treatments don't work, you know, you can have a three-minute does. Thank you for listening to this episode of Instant Genius brought to you from the team behind BBC Science Focus. That was Professor David Nutt. To discover more about psychedelics, you can check out his book. psychedelics, the revolutionary drugs that could change your life. Please note that psychedelics are Class A drugs according to the UK law.

Anyone caught in possession of such substances can face up to seven years in prison, an unlimited fine or both. Information and support for those affected by substance abuse can be found at BBC.co.uk forward slash action line. If you liked what you just heard, then please consider subscribing to Instant Genius wherever you like to listen to podcasts. If you'd like to watch our presenters and guests speaking in person, then you can also check out our YouTube channel at Science Focus.

The current issue of BBC Science Focus magazine is out now. Pick up a copy wherever you buy your favourite magazines or download us on your app store of choice. You can also find us on Apple News or online at sciencefocus.com. This podcast is sponsored by name, audio and focal. The texture and emotional depth of music can be lost through digital sources or poor. signal. Name Audio believes you can have digital precision with analog warmth. Alongside French acoustic specialist vocal, name creates high-end audio systems combining innovation with craftsmanship so you can listen to music, just as the artist intended. Discover more at name audio.com.

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