Rewiring Your Brain for Better Mental Health: How Small Actions Can Transform Your Health with Dr Camilla Nord #543

Have you ever wondered why the same traumatic experience affects different people in completely different ways? Or why finding pleasure in life is so fundamental to our mental wellbeing? To answer these questions and a whole host more, I'm joined this week by Dr Camilla Nord. Camilla leads the Mental Health Neuroscience Lab at the University of Cambridge and is author of the best-selling book, The Balanced Brain: The Science of Mental Health. In this fascinating conversation, we explore: How everything that impacts our mental health ultimately works through the brain, and why we often artificially separate 'mind' from 'brain' and 'mental' from 'physical' health Why pleasure is so fundamental to mental wellbeing that a loss of it is a core symptom of depression, and how activities like social laughter can boost mood by releasing natural opioids The fascinating overlap between chronic pain and depression circuits in the brain – revealing why experiencing one increases your risk of developing the other How motivation varies throughout the day based on our individual body clocks, and why morning people and night owls have different energy patterns Interoception – our internal body awareness – and how practices like meditation, yoga and body scanning can enhance this crucial sense Why the placebo effect is so powerful and how a doctor's communication style can significantly impact treatment outcomes Throughout the conversation, Camilla emphasises that there is no one size fits all approach and that it’s the small, consistent actions that ultimately end up transforming our lives. Support the podcast and enjoy Ad-Free episodes. Try FREE for 7 days on Apple Podcasts https://apple.co/feelbetterlivemore. For other podcast platforms go to https://fblm.supercast.com. Thanks to our sponsors: https://drinkag1.com/livemore https://vivobarefoot.com/livemore Show notes https://drchatterjee.com/543 DISCLAIMER: The content in the podcast and on this webpage is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your doctor or qualified healthcare provider. Never disregard professional medical advice or delay in seeking it because of something you have heard on the podcast or on my website. Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:01Speaker 00

  If what you do is you deprive yourself of everything you love in pursuit of some kind of optimised health for most people, that will not be the route to best mental health.

• 0:11Rangan Chatterjee?

  Hey guys, how are you doing? I hope you're having a good week so far. My name is Dr Rangan-Chatterjee and this is my podcast, Feel Better Live More. Have you ever wondered why the same traumatic experience affects different people in completely different ways? Or why finding pleasure in life is so important for our wellbeing? Well, to answer these questions and a whole host more is this week's guest, the neuroscientist Dr Camilla Naud. Camilla leads the Mental Health Neuroscience Lab at the University of Cambridge and is

• 0:53Rangan Chatterjee?

  the author of the bestselling book, The Balanced Brain: The Science of Mental Health. During our conversation, Camilla reveals how everything that impacts our mental health, from our genes, to our diets, to our stress levels, ultimately works through one final common pathway, the brain. Yet, as Camilla highlights, we often artificially separate mind from brain and mentor from physical health, missing the crucial connections between them. We also discuss how pleasure is so fundamental to mental wellbeing that a loss of it is a core symptom of depression.

• 1:34Rangan Chatterjee?

  Camilla explains the brain's hedonic hotspots and how activities like social laughter can boost mood by releasing natural opioids. We also explore the fascinating overlap between chronic pain and depression circuits in the brain, revealing why experiencing one increases your risk of developing the other. We also discuss the importance of something called interoception, how and why our motivation varies throughout the day, and the incredible underestimated power of placebo. Throughout the conversation, Camilla emphasises that there is no one size fits all approach,

• 2:16Rangan Chatterjee?

  and that it's the small, consistent actions that ultimately end up transforming our lives.

• 2:28Rangan Chatterjee?

  You're a neuroscientist at Cambridge University. What would you say are some of the things we commonly misunderstand about our mental health?

• 2:40Speaker 00

  So in my lab, we study the neuroscience of mental health. And actually, when I tell people that, sometimes they're quite surprised. Because one of the assumptions that really permeates our kind of culture of mental health is in fact that mental health is something ephemeral, psychological, maybe not something that we can kind of tangibly understand if we understood biology. But I suppose, you know, my perspective on this is, in fact, even the most ephemeral sounding things are actually quantifiable, measurable. And so in the case of mental health, I think that the real sort of missing piece of the puzzle is understanding the brain and the things that the brain does that make us feel better or worse, mentally healthier or mentally less healthy.

• 3:25Rangan Chatterjee?

  Yeah, one of the themes throughout this entire book, which has really got me thinking, is that you go through the various causes or the potential causes of mental health problems, genes, cultural factors, economic security, stressful life experiences, the social world, diet, our physical condition, stress, all kinds of different things. But you make it very clear that the final pathway, the common final pathway for all of them to affect our mental health is via the brain, which I think, I guess, makes sense when you think about it logically. But I'm not sure everyone thinks about mental health issues like that.

• 4:07Speaker 00

  I get that. There are so many important factors, the things you've experienced, the world you live in, the way that your genes predispose you, and these all affect your mental health. I'm not dismissing them. It's just that two people with the exact same traumatic experience don't have the same reaction to that traumatic experience. Two people with the exact same genetic predisposition, at least when it comes to mental health traits, it's no kind of black and white binary you want to... Either will or won't develop a disorder. And the reason for that is essentially the complexity of the brain. So sometimes I use smoking and lung cancer as a counter example. So everybody knows that an environmental influence like smoking is quite important

• 4:51Speaker 00

  when it comes to thinking about your likelihood of developing lung cancer. You wouldn't want to dismiss it. But then if you really wanted to understand lung cancer, you would have to study the lungs. Because that is the final common pathway. Whether it's been some other environmental factor, a genetic factor, smoking, whatever has kind of led you there. The final place is the lungs. And to me, the brain and actually the wider nervous system is that place for mental health.

• 5:17Rangan Chatterjee?

  Why do you think that we've not thought about mental health or mental wellbeing through that lens before? Why do you think, I mean, as I say that, I want to explore even the term mental health shortly. But that sort of brain perspective on our mental wellbeing. Do you think that's been missing? And if so, why?

• 5:41Speaker 00

  I think we live in a kind of naturally quite dualistic society. Meaning we all feel there is a distinction between the mind and the brain. And even though I go around saying, and I do genuinely believe that there isn't really a distinction. It doesn't stop you feeling, oh, I am this way. And my brain is this kind of somewhat separate thing about me. Like, for example, you know, another bit of your body. But actually, that feeling of I, that is a consequence of your brain's processes. So in fact, that sort of, that gut feeling, that intuition, that these two things are separate is wrong. They are one in the same, or at least one kind of comes from the other.

• 6:22Rangan Chatterjee?

  I think we could even extend that one step further.

• 6:28Rangan Chatterjee?

  The body and the brain, well, I'm giving my perspective and I welcome yours. I think one of the, one of the problems when we think about our health in general, and let me broaden it out beyond mental health, is that we have separated body and brain. We even have these different terms. I understand why we have those different terms. But it's very clear to me, having seen many patients over the course of my career, that sometimes with some patients, let's say with a mental health issue, helping them do things that you would say are helping their body, it's incredible how many times it helps their mental wellbeing. So, I don't know, exercise or sleep, for example,

• 7:13Rangan Chatterjee?

  can have transformative effects on some people with mental health problems. Not everyone necessarily, but some people.

• 7:20Speaker 00

  I share that perspective entirely, but I didn't always, actually. When I first started doing this kind of neuroscience of mental health research, I, like any other neuroscientist, was really focused, you know, neck up. And actually, it was only maybe a couple of years after my PhD, and I thought to myself, actually, a lot of what the brain is doing is not processing the world around it, but processing the world inside of you, meaning signals from your heart, your gut, your metabolic system, all over your body. So that means necessarily that your physical body is consequential to the brain. So consequential, it's constantly receiving information from it.

• 8:02Speaker 00

  And so I began to kind of, I suppose, delve into body-brain research, and that's actually the major focus of my lab now. And I do think that one of the other ways we kind of get mental health wrong is by creating this artificial division between physical and mental health.

• 8:19Rangan Chatterjee?

  Yeah, so much to talk about there. I definitely want to get to that internal sensing, interoception shortly, because I think it's something that can have a profound impact for all of us if we start to tune into our body's own signals, if we're able to, and if we're able to, let's say, practise. So we can, we can come to that. I really want to talk about these various ingredients for mental health that you write about and you dedicate, you know, separate chapters to, pleasure, pain, motivation, learning.

• 8:53Rangan Chatterjee?

  Because I think we hear a lot about these things. Dopamine, for example, is, you know, the, I think it's the neurochemical of the moment online, right? Everyone likes talking about dopamine. I know you've got some thoughts on dopamine and where we perhaps get misled on our understanding of dopamine. But if we could just start off talking about pain and pleasure. You spend a lot of time at the start of this book, talking about pain and pleasure. And I love what you've written because it's, at its core, let's take depression, for example. There are many symptoms that we look at when trying to diagnose depression.

• 9:33Rangan Chatterjee?

  But, you know, a loss of pleasure or an inability to gain pleasure is one of those symptoms. So can you talk about pleasure and pain and why you think it's important for us to understand them in the context of our mental wellbeing?

• 9:48Speaker 00

  Not everyone knows this, but you don't actually need low mood to be diagnosed with depression. Instead, you could have, their second core symptom is just a loss of pleasure or motivation. So that is so fundamental. It is actually at the centre of the depression diagnosis. That's probably why I first became interested in it. I thought there is this central system, symptom, I should say, that is somehow neglected, both culturally, but also to some degree clinically. It's not as well treated by typical treatments like antidepressants. Often that's the kind of symptom that might remain, even if you see improvements in some of your other symptoms.

• 10:29Speaker 00

  And I thought to myself, but that is so disabling and could actually kind of have this real negative cycle where if you stop getting pleasure from things, stop being motivated to seek out what you used to enjoy, that's just going to self perpetuate. It's just going to make your symptoms worse because you'll stop experiencing the very things that could have helped you get out of a depressive episode. So that was the reason why I began my book on mental health with this kind of deep dive into pleasure and pain, because I think a lack of pleasure is so central to poor mental health. And in fact, experience of pleasure, in my opinion, is central to mental health. Now, pain may be a little more surprising and I think that's why I like it so much.

• 11:14Speaker 00

  People don't think of pain or chronic pain as a mental health syndrome, but I think they probably should because there is so much in common with your experience of chronic pain and your experience of depression. In fact, experience of, say, chronic pain in the past makes you more likely to develop depression in the future, maybe not surprising, it's really hard to have chronic pain. But the other way around is true too. So if you are someone who's experienced depression, you're more likely to go on and experience chronic pain in the future. And in my opinion, that is because there is this biological overlap between the circuits supporting chronic pain and those that we see are dysfunctional in depression.

• 11:58Speaker 00

  And they have to do with your perception of your internal world, your perception of negative beliefs about the world, and these other factors that can make your experience a bit more negative. So that's why I wanted to start with pain. I think it provides a kind of surprising insight into how the brain and the body could come together to change your experience of the world, to make it worse. And then I also think it could maybe provide some clues for how we could get out of it through roots-like pleasure.

• 12:28Rangan Chatterjee?

  Yeah.

• 12:31Rangan Chatterjee?

  It's so interesting. I'm thinking back to a conversation I had with Dr. Howard Schubiner a couple of years ago about treating chronic pain. And one of the things he was sharing with me when he came on the podcast was this idea that physical pain and emotional pain is often expressed in the same area in the brain. You know, I don't want to misspeak, but Howard, that's my recollection of one of the things he was saying to me, which is really, really interesting because you're saying that there's an overlap in the brain between the regions disrupted in depression and in chronic pain. And Dr.

• 13:12Rangan Chatterjee?

  Schubiner was talking about how there's an overlap in the brain between, you know, in those regions that express physical pain versus emotional pain.

• 13:22Rangan Chatterjee?

  It's just hard not to come away from these things with this idea that I feel we've lost a little bit in medicine, that the whole body and brain is interconnected. And whilst it's useful to try and separate things, to study them and see what impact they have, when you're dealing with this kind of three dimensional human being in front of you, as I've done for much of my career, you realise that a lot of these symptoms have multiple inputs, not just one. Does that make sense?

• 13:56Speaker 00

  Exactly. Even something that feels localisable, obvious, like pain. I feel pain in X region of my body. Actually, that sensation is already filtered and modified by so many processes in your body and brain. It's not like a straightforward signal that gets sent to your brain and perceived perfectly. Actually, it depends what else is happening in your environment. For example, if you're escaping a lion, you need to suppress any kind of pain signal as much as possible because your body, your brain, has a priority in its environment that kind of overrides any need to listen to a painful signal. And then in the real world, or in most of our real worlds, there are other priorities that

• 14:40Speaker 00

  can either dampen down or sometimes, you know, upregulate those sorts of symptoms. So it's not as obvious as you might think.

• 14:47Rangan Chatterjee?

  Yeah. Is that why, or is that one of the mechanisms? Let's say someone is an endurance athlete, or they like to do half marathons. So a half marathon, you know, roughly 13 miles, let's say someone's toe starts hurting at mile six, for whatever reason, you know, maybe the way they're running, or their shoe, or something. Endurance athletes will tell you that they can push through. So, you know, they're in the race, or they're, whether they're racing or doing it for fun. And I've been in this situation where you feel something, but through your mind, you just keep going, you get through. And then a few hours later, when you've got home,

• 15:30Rangan Chatterjee?

  Man, it's in agony, or you see something that's red and swollen, but you didn't, you didn't perceive it. It was still there. I'm sure that inflammation was going on, maybe not to the same degree, but it's, it's that perception of pain, isn't it, that's so important?

• 15:45Speaker 00

  Absolutely. And I'm, I'm not a marathon runner, but I suspect what happens in cases like that is two things. One, they have a priority, which is to finish the marathon. And so you can override other kinds of physical sensations. But the other is, they have practice. So often, when you're running long distances, you have various kinds of aches and pains. And actually, you sort of practice suppressing them. You keep going. Perhaps you learn that actually it wasn't that significant. It goes away. And so that sounds quite adaptive, but I think it can also be bad. Although I'm not a very long distance runner, I practice a quite intense form of yoga. And it's very physically intense, I should say. And what

• 16:26Speaker 00

  happens sometimes, I think in my practice, is that I can get injured because I'm so immersed in kind of exactly what I'm doing. Perhaps I'm sort of, you know, you get in sort of almost a meditative state. But also you have these kind of physical goals. And I think that's quite dangerous, because it can mean you're dampening down that sort of listening to information from your body, which could be significant and stop you from getting injured.

• 16:51Rangan Chatterjee?

  Yeah, absolutely. And just to be really clear, I'm not necessarily saying that what that theoretical half marathon runner is doing is necessarily good for them, because of course, you can, you know, cause more of an injury and maybe four months out of the sport and moving because you've pushed through. But I guess the point is, is that pain isn't always what it seems. And we can change our perception of pain in a variety of ways that we're perhaps conscious of and also unconscious of. So in that chapter on pain, you start off by talking about stress and stress induced

• 17:28Rangan Chatterjee?

  And orgesia, which I found really, really interesting. And you spoke about hot and cold bath experiments in the 1980s, skydiving, cold water swimming. So I think we should go into this area because I think it really helps to demonstrate this concept of pain being amenable and it can change depending on what's going on.

• 17:49Speaker 00

  Yeah, I mean, when I was writing that chapter, I had just had a visit by a friend of mine, Jen, who was an expert cold water swimmer. She loves it. She's great at it. And she convinced me to jump into the Cam, which is a very cold river near where I live, around maybe late March, early April. Oh my God, it was so cold. It felt like daggers all over my body. I probably lasted about a minute. And then I got out and I felt, just as she'd predicted, euphoria, like you feel incredible. And that's not just because of the relief of pain, though some of it probably is. It's also because ages ago, we've known for a really long time in neuroscience that kind of just brief,

• 18:33Speaker 00

  but temporary pain, discomfort, very cold water can induce opioid release in the brain. So just like opioid drugs, but endogenous opioids that we have in the body, which you sometimes call endorphins. So they are a reaction. And it helps you do things like push through pain sometimes. Maybe the more mundane experience is if you stub your toe, you feel very intense pain immediately. And then you get almost like a slight head rush and the pain dampens down. And that is an endogenous opioid release.

• 19:05Rangan Chatterjee?

  Okay. Okay. So you go in the cold water and many people enjoy, enjoy, is enjoy the right word? I think they do. I think some people really enjoy.

• 19:17Speaker 00

  They genuinely do, yeah.

• 19:18Rangan Chatterjee?

  Other people don't want to go anywhere near the cold. But how does that help us understand mental ill health? Right? It's interesting. This pain and pleasure concept, I think pleasure we get, right? I think most of us would recognize. Not being able to experience pleasure in life is not going to feel particularly good. But what's the relationship between pain and that cold water immersion and our mental health? I think it would be good to try and draw that link for people.

• 19:52Speaker 00

  Yeah, in many ways, I think it's kind of surprising because the general assumption is that pain is this really negative thing for mental health. And of course, it definitely is if you're experiencing pain all the time. But actually, this kind of very brief discomfort in this case can help acutely, like immediately, with mental health because of this very specific biological mechanism. So I think it proves, or you know, suggests that there are these kind of little short circuit ways that your brain can experience pleasure even from quite surprising sources.

• 20:27Rangan Chatterjee?

  Yeah. What is pleasure? Through the lens of the brain, as a neuroscientist, what is happening in our brain when we experience pleasure? Or does it depend what we're doing to get that pleasure?

• 20:45Speaker 00

  In some ways, it doesn't totally depend what we're doing. Those do change where in the brain is kind of interested in it. But there are very pleasure specific regions that become involved, no matter what the source of pleasure is. These are sometimes called hedonic hotspots, a phrase from Morten Kringlebach and others who are kind of pleasure neuroscientists. And this means that like volcanoes dotted across the surface of the earth, we have these little hotspots of pleasure dotted in our brain. It's actually not, they're not big, and there are not that many of them, but they are really essential and kind of quite characteristic of our experience of pleasure. Yeah.

• 21:24Rangan Chatterjee?

  And do we know what neurochemicals are being released when we experience pleasure?

• 21:30Speaker 00

  So they actually have multiple kinds of neurotransmitters involved in them. But one of the best examples is the opioid system. And there is actually a nice debate about opioids, whether you exactly feel pleasure from them in and of themselves, or whether it kind of depends a lot on the context, which is a fun example of where neuroscientists like to take things quite, yeah, quite literally.

• 21:51Rangan Chatterjee?

  Yeah, you, you mentioned that section on pleasure, that migraine sufferers, or a certain percentage of migraine sufferers, find that having sex actually reduces their pain, whereas you said that with cluster headaches, so that's a different type of headache, having sex can exacerbate their pain. What can we learn from those kind of bits of research?

• 22:15Speaker 00

  Well, what we can learn is that when I initially found out the migraine fact, I thought, this is great, I should tell my friends who get migraines. But in fact, I actually think it can be quite difficult to distinguish between a migraine and a cluster headache for many people. So you might want to be quite careful before you take that kind of advice.

• 22:32Rangan Chatterjee?

  But the fact that we can do something, let's say, pleasurable, right? And it can then change our perception of pain, that's really interesting, isn't it?

• 22:44Speaker 00

  Yeah, I think that is quite significant. And, and actually, sometimes, you know, when you're in a painful state, as we all have been at some point in our lives, it can feel inescapable. And that's part of what makes it so bad, I think, that it can feel eternal. Do you know, if you have even something like a stomach ache, if it goes on for long enough, you just start to, you start to think too much about it. You start to think, oh, my gosh, this is just the way I am. My stomach is just going to feel like this, this is it. And actually, if you can have even temporary relief from those symptoms, it might not necessarily reduce the kind of pain signals coming from somewhere in your body, but it will definitely change your interpretation of those signals.

• 23:25Speaker 00

  The moment you start to think of them as less permanent, less all encompassing, less kind of, this is who I am, then the, the, that's where you get the key to kind of overcoming them and making it through despite those symptoms.

• 23:39Rangan Chatterjee?

  Let's talk a bit about laughter and laughing with friends, because you've, you've been sharing in your book that laughing with friends actually reduces pain. Do we know how it does that?

• 23:51Speaker 00

  This is a good example of what pleasure can do. So what laughter does is it releases endogenous opioids. A really fun experiment that was done. People were watching comedy videos with friends. So this is a social laughter experience, kind of one of the most pleasurable things, I suppose, that humans can do. And so people engaging in this social laughter, not only did they show opioid release in brain scans, proving that there's this kind of biological, like almost painkiller mechanism, but you can even show that in literal painkilling effects, because people were able to do these sort of uncomfortable wall sits and uncomfortable exercise for longer afterwards.

• 24:32Speaker 00

  So that is an immediate effect of having experienced this pleasurable thing on a kind of, you know, a reduction or an overcoming, let's say, of painful inputs afterwards.

• 24:44Rangan Chatterjee?

  Yeah, it reminds me again of like this, this idea that I, I end up talking about quite a lot on the podcast these days is this idea that we can't really separate psychology from physiology.

• 25:01Rangan Chatterjee?

  And what you just said there, that if you are doing wall sits, that sort of like half squat against the wall and seeing how long you can hold it for, you're saying that if you're laughing with friends, watching something, you can actually go for longer. So instead of it being, let's say, 30 seconds that you can manage, that might go to 45 seconds or a minute. So your sense of well-being, what you're doing, your laughter, the kind of hormone and neurochemical release from that allows you to do something physically challenging for longer. And I guess people who do race, whatever sport that might be, and it's well known this when they've studied athletes, is that you can go faster in a race than you can

• 25:45Rangan Chatterjee?

  go by yourself. Because in, I don't know, in the last 200 meters of a race, you can push yourself mentally in a different way if you're trying to beat someone than you can do when you're by yourself. Or for example, in the London Marathon or in, in marathons around the world. If they look at the spread of times, it's really interesting. I think it's quite even and then but just to go just under four hours or just under five hours. There's a disproportionate amount of people who can do that. Presumably they're seeing the clock and they're like, actually, if I just, if I just go into fifth gear,

• 26:26Rangan Chatterjee?

  although I'm tired and I want to stop, I can actually beat this kind of milestone time in my head. It pushes them on, right? So there's this interesting idea about our psychology actually then changes. Or I don't know if you would say it changes our physiology, but it certainly has an impact on our physiology.

• 26:45Speaker 00

  Yeah, I think I probably would say it changes our physiology, at least indirectly by changing our behavior, which then can affect our physiology.

• 26:52Rangan Chatterjee?

  Yeah, and there's also this interesting thing about laughing. Laughter and pleasure is of huge interest, right? I came across some research a few years ago showing us that laughing. Well, it wasn't directly on laughter, it was saying regularly doing things that you love makes you more resilient to stress. And at the same time, chronic work stress makes it harder for you to experience pleasure in those day to day things. So again, this kind of bidirectional relationship. You know, in terms of pleasure, then, if you're someone who is not experiencing pleasure from things that you used to, like, is there a practical take home that people can say,

• 27:36Rangan Chatterjee?

  oh, well, I used to find this enjoyable. I've been diagnosed with depression, I don't anymore. What can I actually do about it?

• 27:50Rangan Chatterjee?

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• 28:33Rangan Chatterjee?

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• 29:12Rangan Chatterjee?

  All you have to do is head to drinkag1.com/livemore to claim this offer before it ends. Today's episode is sponsored by the daily health drink AG1. The clocks are about to change, the mornings are darker, everyone around you seems to be coming down with something and suddenly that wellbeing you felt in the summer seems a long time ago. I certainly know that feeling and that's why at this time of year, I remind myself to lean into the fundamentals. And one of those fundamentals is AG1. AG1 is a daily health drink that has been in my own life for over eight years. And one of the many things I like about it is the fact that many of the nutrients it

• 29:52Rangan Chatterjee?

  contains, for example, vitamin C, vitamin A, zinc and selenium, supports a healthy immune system. Some of the other things I really like about AG1 is that they are committed to continuous improvement and updating their formula as a scientific research involves. And each batch is independently tested for quality and safety markers, including heavy metals, allergens and banned substances. This is how they can guarantee what's in your scoop and what's not. Right now, AG1 is offering a free AG1 Flavor Sampler and AGZ Sampler to try all the flavors plus free vitamin D3 and

• 30:32Rangan Chatterjee?

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• 30:49Speaker 00

  So I suppose the most practical thing for someone diagnosed with depression is to kind of take that signal as being very important and significant, something that they maybe should seek treatment for, psychological treatment, pharmacological treatment, you know, whatever works for them. But I think a second kind of corollary of that that applies to everyone irrespective of their diagnosis is to maybe prioritize pleasure a little bit more than we do. Especially, I think people have this kind of this inclination that everything fun is bad for you. And some fun things are bad for you.

• 31:32Speaker 00

  But actually, when it comes to your mental health, there is a kind of inherent benefit of doing things that you really love, even if some of those things come with small consequences for your health. So I think, you know, it is actually about a balance. If what you do is you deprive yourself of everything you love in pursuit of some kind of optimized health, for most people, that will not be the route to best mental health.

• 31:59Rangan Chatterjee?

  Okay. I wonder if I can share with you an experience I had with a patient quite a number of years ago now. And I have told it, I don't think I've told it on this show for a little while now. Your work and your description of pleasure really makes me think about what actually happened with that patient. So are you open to this?

• 32:20Speaker 00

  Yeah, definitely.

• 32:21Rangan Chatterjee?

  So it was a chap who was, I think he was 53 from recollection.

• 32:28Rangan Chatterjee?

  He was the CEO of a local company. This is years ago now. And he came in to see me with basically a number of symptoms, including low moods and an inability to get pleasure. He was quite indifferent about his life. And I remember seeing him and spending a bit of time and trying to understand his life and what was going on. I asked him about his relationship with his wife. He said, yeah, it's fine. We'd be married for a while. So, you know, he wasn't that excited to talk about it. He said, yes, it's fine. I said, how about your relationship with your kids? He said, yeah, but I rarely see them. You know, they're busy. And what about your job? Do you like it? No, but it pays the bills. He had this very, yeah, nothing really excited him.

• 33:11Rangan Chatterjee?

  And he definitely had symptoms that you could quite reasonably diagnose them with depression. Okay.

• 33:21Rangan Chatterjee?

  And I asked him, do you do anything fun, you know, in your week? Do you have any hobbies? And he said, no, doc, I don't have time for hobbies. And he was basically just saying, I'm too busy. I said, what about the weekend? Oh, the weekend, I'm taking my kids to their clubs and their classes. I don't have time. I've got a busy job. I've got a busy weekend. I don't have time. And yes, I did some blood tests and we did some screening tests and all those sorts of things.

• 33:45Rangan Chatterjee?

  But one of the things I said to him was I sort of probed him about hobbies more. I said, well, what did you used to do? Were there things you used to enjoy? He said, yeah, when I was a kid, when I was a teenager, I used to enjoy building train sets. I said, okay, do you have train sets at home? And he said, well, I do, but they're in my loft. I haven't used them for years. I said, okay, what I want you to do this week, when you have some time or make some time, I want you to get down from your loft, some of those train sets and start playing around with them. Okay, there were other things as well, but I'm trying to just simplify the story to try and get to the point about pleasure. I didn't see him again for a few months, which is not uncommon.

• 34:29Rangan Chatterjee?

  You know, I saw him in NHS general practice. You see so many patients, you can't follow up everyone. But about three months later, I bumped into his wife. And I knew this family pretty well over the years. And she said, Doc, he's like a different person. Ever since he saw you that day, he got the train set down. He started playing with it. He now has subscribed to a monthly magazine. He's going on eBay to buy collector's items. And I actually then saw him about three months later for a well man's check. He came in to get some blood tests done. And I said, hey, look, you know, how are you getting on? He goes, Doc, everything's different now. I feel really, really good. His low mood had gone, his indifference had gone. When I asked him about his marriage, he said, yeah, my relationship's really good. I'm enjoying my job.

• 35:13Rangan Chatterjee?

  I'm closer to my kids. That was so powerful for me, Camilla, because I, it would be easy. Look, I'm always very holistic minded. I'm always trying to get to the root cause of a patient's problems. And I just felt with him, what would happen if we, in some ways, correct the pleasure deficiency in his life or try and address it? And it would seem to me that by engaging in pleasure, and again, I appreciate not everyone can do pleasurable things and feel that pleasure, but he was able to.

• 35:47Speaker 00

  Yeah, he had something.

• 35:48Rangan Chatterjee?

  He had something. He got into it. Everything else in his life came back online, his marriage, his relationship with his kids, his enjoyment of his job. So you're saying that pleasure neurochemically, as a neuroscientist, looking at it through the lens of the brain is very, very important for our mental wellbeing. Can you hypothesize for me what might have been going on? Why did him engaging with his toy train sets, you know, not the sort of thing I learnt at medical school, which is, you know, for depression, prescribe a toy train set? I didn't learn that.

• 36:22Speaker 00

  Yeah, no.

• 36:24Rangan Chatterjee?

  So it's an unusual prescription, but with him it worked. Why do you think that might have been the case?

• 36:29Speaker 00

  Yeah, it's remarkable, actually. And I think it's remarkable because of if you. You draw a line between train sets and mental health. Well, that's going to be a very complicated line. I think for many people, it wouldn't have an effect on mental health. For that patient, it did. And I think the reason for that is actually something that is in common with other, maybe more expected treatments for mental health. So what some pharmacological drug treatments for mental health do is they help you engage in the world a little bit better, perhaps with a little bit less anxiety, and help you re-access the sorts of, say, social pleasures that you used to get. Or what some psychological treatments for depression do is they help you, for example,

• 37:13Speaker 00

  take a little bit of a social risk, see some friends you wouldn't normally see, and essentially also give you a route to that pleasure, or, you know, help you engage with other kinds of activities that you might have previously not. So I think although trains is unique and special, what it is, is it's kind of facilitating that, for me, it's a positive prediction error. So in the brain, we have this kind of predictive model of the world. Otherwise, we wouldn't be able to kind of deal with all of the information that we have. So instead, we learn from what we've experienced. We learn to expect what's happening next. And when something deviates from our expectations, say, when something is better, we weren't

• 37:55Speaker 00

  experiencing any pleasure at all, and then all of a sudden, we have a little dose of pleasure. What that is, is it becomes a positive prediction error, a surprise, that we start, hopefully, to integrate into our model of the world, and eventually, our belief about the very nature of the world can be affected. It can start to become more positive because we've learned that perhaps not 100% of the world is quite so bleak.

• 38:23Rangan Chatterjee?

  Yeah, it's fascinating.

• 38:27Rangan Chatterjee?

  Do you think some of that would have been mediated through dopamine?

• 38:31Speaker 00

  Yeah, so that particular learning process, it's not that the train releases dopamine. That's a kind of, often a misconception, that sort of, if you were to see something you like, that causes some kind of huge rush of dopamine. It's not exactly how it works. It's more that the dopamine is this signal, a signal perhaps of significance, that means this is something you should learn about. So it helps your brain figure out what an unexpectedly positive event was. And when that event is sort of reasonable within your world, then it can get integrated into your wider model of the world. And it begins to affect your future expectations,

• 39:13Speaker 00

  such that actually eventually then it wouldn't have that same effect because it would be expected.

• 39:17Rangan Chatterjee?

  In your RSI talk, which has been seen by many people now on YouTube, you talk, I think, about, is it the early monkey studies on dopamine? About, is it a light and juice?

• 39:31Speaker 00

  Yeah, this is where this process that I'm talking about was first discovered. And it sounds so far away from pleasure and train sets, but it really is the kind of, yeah, the cellular basis of what's happening.

• 39:41Rangan Chatterjee?

  Could you just walk us through it? Because I think dopamine is very much misunderstood and overly simplified. And I think this helps us understand it. And I think then, if I could hear you go through it, I'm then going to try and put it through the lens of that patient to try and hypothesize what might have been going on.

• 39:58Speaker 00

  Yeah, I mean, dopamine gets, it's beloved in some ways or hated in other ways, if you look at it kind of in popular culture. And between those two ends, I'm on the love side. I think dopamine is a fascinating molecule. But perhaps I love it for slightly different reasons because it actually has a number of somewhat neglected functions outside of neuroscience. So things like our ability to initiate movement, that's dopamine. That's what goes wrong in Parkinson's disease. But another of its really central properties is its role in learning. And these are the experiments in the kind of late 1990s that were done, recording from dopamine neurons deep in the brain. And what these neurons do...

• 40:41Speaker 00

  Is if you give monkeys little drops of juice, which they love. Initially, the dopamine fires when they get the drop of juice. They're like, oh, something unexpectedly good. But what the scientists running this experiment did was they paired the drop of juice with a flash of light, like Pavlov and his dogs. So you'd get like flash of light and then drop of juice. And as the monkeys learned to expect the juice, the dopamine response moved earlier and it responded to the flash of light in anticipation of the later juice. And then if the scientists sort of meanly left off the juice one time, the monkeys got water instead, which is fine, but not as good as juice. Then there was a dip.

• 41:23Speaker 00

  So the dopamine cells reduced their responding because that was worse than what they were expecting. After a flash of light, they were expecting juice, they got water. So this is called a prediction error. And it's something that our brain does in all sorts of contexts. When you experience something that is different than what you're expecting. And in this context of kind of rewards and losses, dopamine is a really central player in sending this signal in the brain.

• 41:48Rangan Chatterjee?

  And is this related to one of the reasons we feel that a lot of these modern apps, let's say, social media apps, have the potential for people to engage in addictive behavior with or to have a compulsive relationship with those apps? Is because the reward is unpredictable. So you, you know, you may associate, you may initially really enjoy being on the social media app. So your dopamine is releasing and then it's in advance. You know, you're going to sit on the sofa in five minutes and have time to chill. So the dopamine release starts to come earlier. But then sometimes you go on and things are great. Sometimes you go on and they're not. So that unpredictability, that's all mediated through dopamine, right?

• 42:30Speaker 00

  I think the unpredictability does contribute to why people sort of keep scrolling, even if they haven't had fun so far. Because it might, I suppose there's always this chance that they might see something really enjoyable. But I actually think people use social media for lots of reasons. And probably the kind of reward addictiveness reason has.

• 42:51Speaker 00

  Maybe gotten all the publicity, but I think a lot of people use it because like they find boredom so aversive. There's a famous psychology experiment from maybe about 10 years ago, I think, where people were put in a room with a shock box, which is like a box where you can deliver yourself a painful stimulus. And they were told how it worked and then they were just left. And basically loads of them just set it up on themselves and gave themselves a painful shock. And that's because, one, humans are like incredibly curious. And two, because they didn't really just want to be there bored on their own with something that could give them something different, I suppose. So one of the interpretations of that is boredom is extremely aversive.

• 43:33Speaker 00

  And what people use social media for often is in those in between times. Yeah.

• 43:40Rangan Chatterjee?

  Let's go back to this patient for a second because I'm truly fascinated by our inability to feel pleasure. You know, why that happens then, how in this patient at least, engaging is something that he hasn't engaged with for a while that used to give him a lot of pleasure as a young boy or as a teenager, seemingly started to change his life around.

• 44:05Rangan Chatterjee?

  Might it be, for example, that he goes back to his house that evening, he gets the train toy set down. And then he surprisingly finds, actually, this is really good fun. I forgot how much I enjoyed this, right? So he, because it's, you talked about our expectation, that is maybe surpassing his expectation. He didn't think it would be that good, but it was actually really good. He's like, oh, wow. So it's better than he expected, which is a good thing for us. We feel happier. We feel more positive. And then let's say he played on that, that, that, that train set twice a week. Could it be that?

• 44:45Rangan Chatterjee?

  You know, he's getting to the point, because he enjoys it, that he's finishing work in the evening and it's, you know, it's five, five thirty PM, he's writing emails and he goes, hey man, just let's crack through this because in an hour I'll be home and I can start playing. So his dopamine starts to be released even at work in advance of him doing that. Does that sound reasonable, that this could be one of the, one of the mechanisms by which he started to turn his life around through pleasure?

• 45:12Speaker 00

  Yeah, and it's just kind of like one little tweak. And then I think it will have had, you know, a lot of knock on consequences. For example, it will have helped him feel perhaps some kind of fulfillment or connection, because if he started subscribing to magazines and feeling like this was kind of, you know, maybe he was part of a community that he hadn't been part of before. It also perhaps would have helped him access, you know, one of the other ingredients that I think is really essential for mental health, which is motivation. So it maybe will have given him a kind of invigoration for something that he didn't otherwise have. You know, an apathetic state is not a very pleasant one to be in. You feel, you know, maybe neutral, but actually it stops you from engaging

• 45:55Speaker 00

  in things in life. And that, no matter what it is, if it's something that really motivates you, gives you that kind of get up and go, then that is often a really important access to things that could give you pleasure and happiness and so on.

• 46:08Rangan Chatterjee?

  What is motivation?

• 46:10Speaker 00

  I think of motivation as, so I sometimes use the word drive for it throughout my book, because it can mean this ability to go from a state of passive reception to a state of kind of active engagement. But there's a cost to that. So motivation inherently comes with a cost. As soon as you exert effort, cognitive effort even in your mind, but especially physical effort, you have an energetic cost to the body. And our brain doesn't necessarily want to spend that cost. So everything that might take energy is something that we weigh up. Is it worth doing this thing for the possible either reward or alleviation of punishment? And these can be

• 46:54Speaker 00

  Very abstract, distanced things. And people have actually slightly different kind of models of this. So people are, some people are a little bit more sensitive to the cost of what effort might come, like the potential cost of effort. Some people are really quite sensitive to like little, small fluctuations and how rewarding something would be. And they would, you know, maybe give much more effort to something more rewarding and much less effort to something less rewarding. These are all kind of interesting differences in the population.

• 47:21Rangan Chatterjee?

  Yeah, I love the idea that motivation has a cost. I've never really thought about it through that lens before. And it makes me think of something Daniel Lieberman. Do you know Professor Daniel Lieberman at Harvard? He writes in his book Exercised about this idea that basically, you know, we're not born to exercise. Ultimately, if you go back to a hunter gatherer tribe or today, let's say you go to the Hadza tribe in Tanzania and ask them to run for an hour on a treadmill. I mean, they'd be totally confused. What, just run and not go anywhere and be on the same spot? Yeah, it's the most bizarre thing in the world, but obviously it's our way of trying to cope with the modern world where we're not moving enough.

• 48:05Rangan Chatterjee?

  Or we're certainly not moving as much as our ancestors used to move, right? So he makes the case in that book that actually, don't feel bad that you don't want to exercise. You're not meant to, right? It's not that there's a failing there from you because obviously the body's trying to conserve energy, right? If there's no reason for you to go and move your body, why would you? And I feel that it's a similar analogy, a similar theme through the way you're talking about motivation. Don't feel bad necessarily if you're not motivated to go and do all the things that you see the other people around you doing. And you go, why, why have I not got that motivation?

• 48:44Rangan Chatterjee?

  I think it's quite reassuring for people, at least initially to go, yeah, because maybe, maybe you're knackered and maybe your brain's going, actually. I'm not going to give you motivation at the moment because you need to rest. So I'm going to make you tired. So all you want to do is sit on the sofa and recoup your energy. Does that make sense through your model?

• 49:04Speaker 00

  Sometimes that's exactly what your body wants you to do. And I think one thing that's quite interesting is that there are actually a number of variables that go into this effort cost equation. And one of them is actually the time of day and your circadian rhythm. So we all feel a little bit lazier at night and a little bit more motivated during the day. But in my lab, my PhD student Sarah Merhoff did a series of experiments showing that actually this really depends on your chronotype. If you are a morning person, then that kind of person shows this very different equation, an equation really on the side of effort and motivation in the morning. And then that dips as the day goes on, exactly as you would imagine.

• 49:49Speaker 00

  But it makes them look almost apathetic. If you test them in the afternoon, it makes them look actually exactly like people who have high levels of apathy, high levels of anhedonia, which is that lack of pleasure. And then the flip side is true for people who have late circadian rhythms. I think we initially thought they would just look like people who were a little bit apathetic, had perhaps higher levels of depression, who also show this shift away from energy, away from effort. But they only look like that in the morning. If you test people who are essentially night owls, people who really get a lot of their energy later in the day, then they show this ability to engage in effort, engage in physical

• 50:34Speaker 00

  cost as the day goes on, more as the day goes on than they do in the morning.

• 50:38Rangan Chatterjee?

  Yeah, that was truly fascinating. It makes you think as a doctor, when you're assessing someone, it kind of depends on what time of day you're assessing that patient.

• 50:48Speaker 00

  Exactly what I thought from it, yeah.

• 50:49Rangan Chatterjee?

  Of course, the assessment on mental wellbeing isn't just about what happens in that moment. It's over the course of a few weeks and a few months. But I'm definitely that kind of morning person. I mean, no question at all. If I don't get my stuff done in the morning, my... You know, all the things that I like to do, my journaling, my meditation, my movements. You, once it hits 3pm, I ain't gonna do a lot of that stuff. I'm not gonna start working out, I'm not gonna go for a run. Whereas other people can, that isn't the time for me. And I think that has wider implications beyond mental wellbeing in terms of just our productivity, our work, you know, understanding yourself and when you are more energized and when that motivation,

• 51:34Rangan Chatterjee?

  I guess, comes a bit more naturally.

• 51:36Speaker 00

  Yeah.

• 51:36Rangan Chatterjee?

  It's probably good to know that about yourself, isn't it?

• 51:38Speaker 00

  I think so, and I think kind of harness that because many people sort of expect to be able to work at a consistent level throughout their day, throughout their week. But actually, that's quite outdated because most of us don't do jobs where you have to just do the same thing again and again, and it's really about the number of hours that you do that same thing. Actually, if you have the sort of job where what you produce is what matters, kind of the quality of what you produce, then you probably need to modify your working based on your best hours, and that's how you're gonna get the best output.

• 52:10Rangan Chatterjee?

  Yeah, and that's something I was speaking to Cal Newport about. He wrote a book about this last year about we need these new ways of working. The neuroscientist and i surgeon, Mitesh Steroni, I spoke to a few months ago about this idea that we're no longer in the factory where we need to clock in and just do a mundane task for eight hours, and when we're done, we clock out and go home. Like, a lot of this work now, this modern work, is using brain power. It requires creativity, problem solving. You cannot stay at the same pace and the same ability to do that for eight hours in a row, you know, you're gonna be better at certain parts of the day, which is why I

• 52:48Rangan Chatterjee?

  think a lot of companies who are able to give their staff a bit more autonomy, I think are probably gonna get better results from them and probably better rates of wellbeing, I would imagine.

• 53:02Speaker 00

  Yeah, for sure, yeah.

• 53:02Rangan Chatterjee?

  You know, there's a statistic that was published maybe about a year, year and a half ago in the UK, saying that 88% of UK workers have experienced a degree of burnout in the past two years, which I think is a pretty worrying state for modern society, at least in the UK. What is the relationship between chronic stress and chronic work stress, do you think, and our mental wellbeing?

• 53:37Rangan Chatterjee?

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• 54:20Rangan Chatterjee?

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• 54:59Rangan Chatterjee?

  All you have to do is head to drinkag1.com/livemore to claim this offer before it ends. Today's episode is sponsored by the daily health drink AG1. The clocks are about to change, the mornings are darker, everyone around you seems to be coming down with something and suddenly that wellbeing you felt in the summer seems a long time ago. I certainly know that feeling and that's why at this time of year, I remind myself to lean into the fundamentals and one of those fundamentals is AG1. AG1 is a daily health drink that has been in my own life for over eight years. And one of the many things I like about it is the fact that many of the nutrients it contains, for example, vitamin C, vitamin A, zinc and selenium, supports-

• 55:43Rangan Chatterjee?

  Healthy immune system. Some of the other things I really like about AG1 is that they are committed to continuous improvement and updating their formula as a scientific research involves. And each batch is independently tested for quality and safety markers, including heavy metals, allergens and banned substances. This is how they can guarantee what's in your scoop and what's not. Right now, AG1 is offering a free AG1 flavour sampler and AGZ sampler to try all the flavours, plus free vitamin D3 and K2 and AG1 welcome kit with your first AG1 subscription order.

• 56:24Rangan Chatterjee?

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• 56:42Speaker 00

  Yeah, that is a really, a really sad statistic because actually if you experience chronic stress, it has effects on mental wellbeing, but those effects come essentially physical by physiological processes. So it changes levels of cortisol, other kinds of important hormones. It also changes things like how exhausted you feel, which is part of your sort of brain's computation of your own mental health. It also probably changes the way and the time that you have to engage in, I don't know, playing with train sets or other fun things. So I think actually that kind of chronic stress and burnout can have direct and loads of indirect consequences on your mental health.

• 57:23Rangan Chatterjee?

  Yeah, and anhedonia, the inability to experience pleasure is also a sign or a symptom you will often see in burnouts, you know, although yes, it's a symptom that's used in the diagnosis of depression. It's not exclusive to depression. You see it in other things as well, and I've certainly seen it in patients chronically stressed, on the road to burnout or even at burnouts. That's just this apathy and this, you know.

• 57:54Rangan Chatterjee?

  Just this reluctance to want to do anything, which is pretty sad, really.

• 57:59Speaker 00

  Yeah, and how do you get around that? I mean, I think it's a real, I think it's a conundrum.

• 58:04Rangan Chatterjee?

  Yeah, how do you get around it? Okay, let's take this beyond burnout. How do you get around this when people are feeling as if they're in a really dark hole and they just don't know how to get out of it? We can talk about drugs in just a moment. I once had a suicidal patient for a variety of different reasons. And the way I helped them to get out of it was through five-minute interventions. And I really would love to hear your view as a neuroscientist on what might be going on here. I have found, whether with this patient or patients with depression over the years, there's not a feeling that they're making progress in life.

• 58:49Rangan Chatterjee?

  Okay, they're not moving forward. So years ago, I realized, okay, how can I help this patient feel as if they're making progress? Because a lot of the things they get asked to do, or they read online, the truth is when you feel really, really low, you know, you're probably going to struggle to motivate yourself to get to the gym and move your body in a way that's going to increase your endorphins, for example, right?

• 59:15Speaker 00

  Absolutely.

• 59:16Rangan Chatterjee?

  So I came up with this sort of five-minute concept that I use myself. So I have a five-minute strength workout every morning in my kitchen, in my pajamas. But with many of my patients with depression, I said, well, what is one thing that we can get you, what is one thing you might want to do? And I'd always personalize it to them. But I remember one suicidal patient, it was working out, right? They wouldn't go to a gym, they said they haven't got motivation. And I broke it right down. I said, what would it look like if you did five minutes every morning? And for that patient, they used to work out when they were a teenager. So they were quite familiar with that as a concept. So this person bought a kettlebell. Kept the kettlebell in their kitchen.

• 1:00:00Rangan Chatterjee?

  And again, this is not about the kettlebell. It's not about it being exercised. This is what that patient wanted. And you make it very clear in your book. There is no one size fits all, which I completely agree with as in terms of a solution. But we started off, we're saying, okay, what would it look like if every morning, the first thing you do when you come in your kitchen, you literally pick up that kettlebell and you just swing it on and off for five minutes. Right. And I think we started with two minutes and built up to five minutes. I'm not kidding you. That was the start of all the changes because by doing that every morning, because I made it so simple that he could never really say, he could do, but he didn't say, I don't have time or the motivation. I said, even put it in your sink if you have to.

• 1:00:44Rangan Chatterjee?

  So you have to at least move it to get it. You know, I was really trying to help him go, no, you have to pick that thing up. And my, my feeling was, was that doing that every day changed the way that he viewed himself. Instead of being someone who didn't have motivation and didn't have this ability to do anything. It's like, no, he started doing that within seven days, within 40 days, within 21 days. He's now someone who actually, yeah, man, I actually, I can do stuff. And then yes, it's working on his muscles, his hormones are changing, his dopamine will be changing, maybe his serotonin is changing. But that was me trying to help him as a clinician. Right?

• 1:01:27Rangan Chatterjee?

  I didn't need to know what was the neuroscience going on. I'm just like, how do I help this person? What do you think might have been going on from a neuroscience perspective?

• 1:01:37Speaker 00

  Yeah, I love that five minute idea because actually what you've just done in that effort cost equation that we are all kind of subject to is you've made the cost smaller and smaller and smaller. And in some ways, you've actually kept the reward constant, the reward of getting to do something, which he wants to do, like exercise, but you've made it even more accessible and even less effortful to do. So until the point where it's a kind of inflection point. Where it was worth it for him. And that will have been the initial cost for him. But actually, the cost will even have reduced over time. Because as something becomes a habit, it becomes almost easier to do than not do.

• 1:02:21Speaker 00

  So the hardest change is that first change, which you kind of enabled with that intervention.

• 1:02:28Rangan Chatterjee?

  That's interesting. When it becomes a habit, it's harder to not do than do. That's a really interesting concept, isn't it? I guess that's how I would even look at my morning strength workout now. It's been over five years since I've been doing this. And it's just five minutes while my coffee brews every morning. You know, you may not have heard me talk about this before, but essentially while the coffee brews for five minutes, I'm in my pajamas and I'm doing a strength workout in the kitchen. I'm not going on email or Instagram in those five minutes. And I actually think my morning would feel really weird now if I didn't do it.

• 1:03:07Speaker 00

  Do you ever skip it?

• 1:03:09Rangan Chatterjee?

  Very, very rarely. Even when I travel, and I've been traveling a lot recently, I even take my cafetiere with me. Right, and my coffee.

• 1:03:19Speaker 00

  That's your timer, so you've got to.

• 1:03:21Rangan Chatterjee?

  Yeah, but what it does is when I'm on the roads and I've been doing a lot of interviews for my book recently, so I've been on the road a lot, in a hotel room in the morning, because I drink black coffee. It's easy, you just boil a kettle and you make it and I put the timer on and I do it in a hotel room. So for me, it's actually this little habit that I take around with me to sort of ground me and center me every morning. And yeah, I'm just wondering, because you know, we started off this conversations talking about this idea that permeates your entire book, which is whatever's going on, whatever we're doing that's improving our mental wellbeing, it's always happening through the brain and the nervous system. So I'm truly fascinated as to what these five minute actions are doing.

• 1:04:03Rangan Chatterjee?

  Can you hypothesize what kind of brain chemicals might be changing?

• 1:04:08Speaker 00

  What will be changing are specific circuits in the brain that are involved in this kind of instantiation and then maintenance of habits, which are sort of. Of two different circuits. So the first time you do something effortful, it involves regions in the brain that work on that computation. How costly is it? How rewarding is it? Is it worth it to me? And those are the regions we know from animal experiments and also human experiments that say if you have an injury in them, it can really change this cost benefit calculation. So that's how we know that they're related. And it does involve neurotransmitters like dopamine, but not only. So it's really about the kind of communication between these different regions that help you make that decision.

• 1:04:51Speaker 00

  But as something becomes a habit, actually, the circuits change from kind of decision making circuits, which often involve, you know, weighing up possible options. It's a little bit more effortful for the brain, that is, to these quite automatic circuits that make something a habit. You hear actually most about these circuits, places like the nucleus accumbens, dopamine-rich regions of the brain, because of their involvement in drug addiction. But it's not just drug addiction. These are the circuits that help us do things again and again without using all of our cognitive resources to focus on them. So we move into this other kind of mode of processing in the brain,

• 1:05:34Speaker 00

  something that can be ongoing, almost in the background, while our brain is doing other things or can be focused on other things.

• 1:05:40Rangan Chatterjee?

  So this is the same process that when you're learning to drive a manual gear car, or for the transatlantic audience, a stick. In those first few driving lessons, you're utilizing, it's hard work. You know, you're trying to figure out how to time the clutch with the gear changing without stalling the car.

• 1:06:01Speaker 00

  Yeah, like the speed of coming up.

• 1:06:03Rangan Chatterjee?

  Yeah, so that's presumably quite a lot of effort for your brain.

• 1:06:06Speaker 00

  Boy, can you not think about anything else when you're learning to drive a manual car?

• 1:06:10Rangan Chatterjee?

  Exactly. But then at some point, it becomes automatic. And then when you have to teach someone, how do you do that? You don't actually, you don't actually know how you do it.

• 1:06:19Speaker 00

  Yeah, in fact, you might become worse if you start thinking about it. Like when you're walking downstairs and you kind of forget.

• 1:06:23Rangan Chatterjee?

  Yeah, it's like, you know, golfers when they choke in the final few holes of a major. You know, one of the theories which I think makes the most sense to me is that instead of doing something that's just habituated and automatic, they're just looking at the hole, they're swinging the club, they're now trying to control every aspect. This matters, I've been training for this since I was four years old. And suddenly they can't actually swing the golf club anymore because they're now overly thinking about it. This is the same principle, right?

• 1:06:51Speaker 00

  Exactly, yeah. It's a shift to a... They're often actually very proximal next to each other anatomical brain regions, but they are involved in these two kind of complementary action processes, processes that support our action. One of them, very effortful, involves lots of cognitive control, things like that. One of them, automatic, habitual and so on.

• 1:07:14Rangan Chatterjee?

  When we think about these four brain processes, which of course are linked, pleasure, pain, motivation and learning, I'm just thinking that a lot of people are trying to change their habits, okay? At various stages in their life, they're trying to implement certain things. And so initially, when we try and implement those things, it can feel hard. So let's use that five minute workout for that patient, right? As a model.

• 1:07:46Rangan Chatterjee?

  The patient feels apathy.

• 1:07:50Rangan Chatterjee?

  They feel indifferent, they don't have motivation.

• 1:07:54Rangan Chatterjee?

  They start doing something where together we've lowered the cost right down. Hey, hey, this is super easy, even just do one minute, okay? Right, so they do that, so we've lowered the cost. So they start doing it. And presumably at some point, those endorphins from, you know, swinging kettlebell will start to be released, you know? So it's going to help you feel good. So it's going to perhaps give you some pleasure?

• 1:08:19Speaker 00

  Yeah, and it may become much more kind of self reinforcing than it would have been before. Because before, you had to kind of imagine that it would be good. You probably didn't even have that solid a concept of how good it would be, whether it would be at all, you might have been actually quite uncertain. And as you experience it, if it is good, your estimate of that kind of future feeling becomes more and more and more precise statistically. And so you are able to predict just how good it will be and the likelihood that it will be good much better. That makes it more rewarding.

• 1:08:54Rangan Chatterjee?

  And presumably that then speaks to this idea that if you want to increase the movement in your life, whether it's for your mental wellbeing or your physical health, not that we could separate them as cleanly as that, ultimately you want to find something that you do find enjoyable.

• 1:09:10Speaker 00

  Yeah, I think it's a much, much harder road to try to engage in something that you kind of conceptually know is good for you, but that you get literally no enjoyment out of. It's possible, you know, you really have to work your kind of motivation system hard. There are some highly, highly like motivated people who can ignore the cost of that, who engage in it, but boy, is that a rough road to go down.

• 1:09:35Rangan Chatterjee?

  Why that movement snack concept is something that I'm so passionate about.

• 1:09:40Speaker 00

  Movement snack, yeah, I love that term.

• 1:09:42Rangan Chatterjee?

  Yeah, because it's, A, it simplifies movement right down. It's helped me, no ends, it's helped, I'm going to say thousands of my patients over the years, because I think it does something beyond what we might hypothesize that movement is doing. So we often look at these things, oh, you know, when you move, it's going to release myokines in your body, it's got an anti-inflammatory component, it's going to help your muscles, which is then going to help your insulin sensitivity. I don't disagree with any of these things.

• 1:10:10Speaker 00

  Sure, but you think it does this kind of self-efficacy thing where it like makes you realize you can do it.

• 1:10:16Rangan Chatterjee?

  Yeah, I think for me at least, my observations are that that might be the gold behind some of these things. But don't get me wrong, those other biochemical changes for your physical health are fantastic, but I think that's what it does, you know, and I think it maybe targets that motivation piece and makes people feel that they can do stuff.

• 1:10:38Speaker 00

  Yeah, I think you're right about that. I think it is motivation that becomes the crux, you know, the, the kind of, maybe it's a little bit, a little bit of pleasure, a little bit of a prediction error, but actually I think that getting people able to do something that they want to do, kind of finding access into their motivation system could make, it could be really black and white, it could make you all of a sudden realize you can do things, you can feel motivated, you can change things and so on.

• 1:11:07Rangan Chatterjee?

  In your book, you talk about this term, mental health, and you also sort of split it up at various places to, you know, mental health is this broad term, there's mental illness within that, but I guess there's also mental wellbeing. I don't know how you feel about this. I've always struggled with the term mental health. I know it's commonly used and I've used it as well, but I would say it never really connects with me. Like, I never really intuitively know what does mental health mean? And of course, that will be because of my perception of the world and what associations I have with that term. How do you see that term? And how do you see the differences between mental illness, mental wellbeing?

• 1:11:51Rangan Chatterjee?

  And, you know, how do you sort of parse those all together in your brain?

• 1:11:56Speaker 00

  I thought very deliberately about whether or not to use the phrase mental health. I think it gets thrown about in all kinds of different ways and sometimes used interchangeably with mental illness, which is really unhelpful. But I also have some problems with the idea of mental wellbeing or wellbeing in general, which is probably why I went with mental health. Because actually, I think there is value, for example, if you are in a really low state, into feeling just healthy. Not necessarily great, not necessarily splendid, not any of those other kind of, you know, wellbeing type terms. But actually, the ability to function is the biggest difference

• 1:12:40Speaker 00

  between mental health and a lack of mental health. And I actually think that boundary is the kind of critical boundary. And that's where I wanted to write my book. So it's also about, within mental health, how you can feel better. But really, a lot of what matters to most people, all of us will have either, you know, known someone who experiences a mental health condition or experienced one ourselves, is how to get over that boundary into mental health.

• 1:13:08Rangan Chatterjee?

  Many people would say that our mental health is currently declining.

• 1:13:14Rangan Chatterjee?

  You've written this wonderful book on mental health. Do you think it's fair to say that as a society, things are getting worse? Or do you think there's other things that explain that?

• 1:13:27Speaker 00

  I'm very torn on that. There is data to suggest that more and more people are diagnosed with a mental health condition all the time, especially younger people. But there are a lot of problems with that data. So some of it is a good thing. It means people are accessing services, accessing diagnoses when they might not have in the past. Some of it means, you know, perhaps you might have felt shame for feeling this way before. And now people are able to kind of come forward, seek help, get treatment for it. And that looks like a rise in rates of mental health diagnosis. So that explains some of it. But I suppose if you really dig down, I don't think it explains all of it.

• 1:14:11Speaker 00

  There is still data suggesting that if you ask people the same exact questions, especially young people, especially young females, over time, their general wellbeing, general sense of mental health does seem to be worse than it used to be. So it's perhaps not as dramatic as some of the graphs would show, but it is happening. And I think we don't really know why.

• 1:14:36Rangan Chatterjee?

  Do you have any hypotheses as to what the big things are in society that might be contributing to this?

• 1:14:43Speaker 00

  I think it may be a lot of little things, in fact. So many of the young people tested at the moment are people who experienced the pandemic at very critical ages in brain development, which means they were deprived of socialisation at really critical periods. It means they experienced something quite traumatic at a very critical period. And so that will definitely have had a knock on effect on long term mental health. So I think that's kind of one contributor, maybe in that case, not a very small contributor. I also think there is a role, you know, potential role for the conceptualisation of mental health problems. In and of themselves. So it sounds very complex, but this is an idea that has gained

• 1:15:28Speaker 00

  traction in my field, that actual awareness of mental health can sometimes make mental health problems worse. So it can make you aware of your symptoms, but it can also make you kind of focus on your symptoms, consolidate your symptoms, perhaps enhance your symptoms, especially in social settings in adolescence. So this is a kind of testable hypothesis that I would say has not been proven by any means, but is a kind of one reasonable explanation for why there might be especially kind of concentrations of mental health problems emerging in some people.

• 1:16:03Rangan Chatterjee?

  Yeah, it's really, really interesting. I think it's pretty reasonable to think that for some people that may well be the case.

• 1:16:08Speaker 00

  I think it's reasonable, and I think one of the reasons why it's kind of plausible is because this can happen even with physical symptoms. So we know that in certain social settings, if, for example, you know, the kind of classic example is often teenage girls, but it really doesn't have to be. It can be kind of any concentrated intense social setting, often in adolescence. You can see a transmission of physical symptoms in certain communities, pejoratively sometimes called like mass hysteria, but actually it's a real process that is not conscious, that can just happen in experiencing someone else with very, very like kind of profoundly different physical symptoms. You can have a kind of contagious effect.

• 1:16:53Rangan Chatterjee?

  Yeah, and we see this in all kinds of different things. You know, we are social animals and that we respond to what the people around us are doing and what they're feeling. You know, there's studies showing that when you walk or run in groups, your cadence and rhythm starts to become more and more similar.

• 1:17:11Speaker 00

  Yeah, synchronized.

• 1:17:12Rangan Chatterjee?

  Synchronized, yeah, which is fascinating. And, you know, that idea that we're social animals and the fact that

• 1:17:21Rangan Chatterjee?

  In the lockdowns, there may well have been and still be a serious impact on certain people from that isolation. I know you mentioned it in certain young people, but we've seen this in a lot of the elderly as well, in older people who literally changed in those few months of lockdown and they've never returned. I remember so clearly, maybe between the first and the second lockdown, I went to my local leisure centre to go for a swim and hadn't seen that manager for months. We had a chat and he goes, man, people have changed. He says, I used to see six months ago, these like 15, 16 year olds that come in, they'd be chatty, they'd be talking. He says, A, they're not coming in and when

• 1:18:03Rangan Chatterjee?

  they do, they're withdrawn, they're not looking them in the eye. You know, we, we, we sometimes don't think enough about how important that social interaction is for our physical and mental wellbeing. And it reminds me of what you were saying before about laughter, laughing with friends can make you go longer on a wall sit. Laughing with friends, you write about in your book, reduces pain. And you, you put in a hypothesis, I think, for one of your colleagues, that opioid activity may be a safety signal, calming and relaxing people to facilitate social cohesion. I thought that was fascinating. Do you remember who that researcher was?

• 1:18:44Speaker 00

  Yeah, I love that hypothesis. So I think that was written by Sophie Scott, Carolyn McGeadigan and Nadine Levann.

• 1:18:49Rangan Chatterjee?

  Yeah.

• 1:18:49Speaker 00

  Yeah, who are all these kind of laughter neuroscientists, speech neuroscientists.

• 1:18:53Rangan Chatterjee?

  Can I just say, laughter neuroscientists.

• 1:18:55Speaker 00

  I know, I know. They've got such a good gig. But I particularly loved that idea, that laughter is this kind of mechanism to enhance social cohesion. And there was a study that they wrote about in that paper that I still kind of use in my day to day life now, which is that when you're having a fight with your partner, it turns out that people who laugh during their arguments with their partners, they kind of made couples fight in this experiment, very, very cruel. And the ones who laugh report higher levels of marital satisfaction, kind of less importance of the fight, and then crucially show fewer physiological signals of stress during the fight, things like cortisol, hormones like cortisol.

• 1:19:36Rangan Chatterjee?

  So basically, what I got from that was that couples who laugh together regularly, when they then have a bit of conflict, which for whatever reason, You know, the stress is lower, they recover from it quicker, I think, all these sort of things. Is that, is that your recollection?

• 1:19:53Speaker 00

  I think that's true too, but I actually think it was people who managed to joke a little bit during the argument, because that it has this, I think it has this immediate effect on your physiology. That's why you see those physiological signs. So it would be, yeah, people who can kind of find a way to take a step back. But I think what you said is also true in this experiment, that people who kind of laugh together do have a kind of better response to argument.

• 1:20:19Rangan Chatterjee?

  So one of the take homes from this conversation, whether it be for mental health or mental wellbeing, or just generally improving your satisfaction and your sense of wellbeing in the world is laugh more. Right? Is that reasonable?

• 1:20:32Speaker 00

  I think it's reasonable.

• 1:20:33Rangan Chatterjee?

  And do we think from your laughter neuroscientist friends, man, I'm going to have to get a laughter neuroscientist on the show, that's, that sounds wonderful as a job.

• 1:20:45Rangan Chatterjee?

  Do you know from your interactions with them, what laughing by yourself does?

• 1:20:51Speaker 00

  So I am interested in this because often they use, you know, in this field in general, they use social laughter as the kind of example, but then they use single laughter as the, you know, as the stimulus. Like in an experiment, you put people in the scanner and they might be listening to, for example, real or fake laughter, you can see brain differences there, or they might even be laughing themselves, although that's actually quite difficult because the brain can't move in the scanner. But you can sort of measure what ends up happening with vocalizations when someone is laughing. So I'm always quite interested that the way experiments have to be done as a scientist are sometimes solo.

• 1:21:32Speaker 00

  But then the implications that that has kind of for our communities, for our societies are not solo at all. They're conjoined, they're all together.

• 1:21:41Rangan Chatterjee?

  Yeah, I mean, it'd be, it'd be interesting to know the difference. I mean, I know on a personal level, if I'm ever feeling a bit overworked or. You know, I just put on YouTube and watch a comedian for 10 minutes. Then you just laugh and you get taken to another world. You feel completely different. You know, you feel like you've gone to a different place. My perception, I haven't measured this, but my perception is that my stress levels are lower. I feel better about the world.

• 1:22:08Speaker 00

  Oh, that's definitely true. I think, but what's interesting is that that's hard. It's harder to laugh on your own. People laugh much more easily at much less funny jokes when they're with other people. So social after is more accessible. I don't know if it's different, but it's easier.

• 1:22:24Rangan Chatterjee?

  Wow, truly fascinating. Okay, we can go down a laughter rabbit hole.

• 1:22:27Speaker 00

  Yeah, we could, yeah.

• 1:22:28Rangan Chatterjee?

  Stop us from doing that. Right, let's think about some things that we can do treatment wise, okay? And I really, really love, because it, because it so aligns with my view on the world, that there's no one size fits all for improving our mental health. You make that point at multiple times throughout your book. And you also say, we need to get away from this idea that something works or it doesn't work for mental health. One person's miracle is another person's snake oil. I thought that was really interesting. I wasn't expecting to read that from a neuroscientist. What do you mean by that?

• 1:23:06Speaker 00

  I genuinely think this is what we now know in neuroscience, in kind of the science of mental health more generally, which is that treatments that in the past we maybe had a binary view of, antidepressants in general work, other things might not work in general. Today, we have a much more nuanced view of what it means to work and also what it means to not work. So there's, there's a general acceptance that kind of nothing works for everyone. But I think also there is a real kind of growing understanding of there's a reason why for that, that in fact, there might be, the thing we call depression might actually be caused by different mechanisms.

• 1:23:50Speaker 00

  And so that's why one thing might work to treat one person's depression, but a totally different thing might work to treat someone else's depression. Because actually, the processes in your brain and body that are kind of causing that state are different and so are differentially affected by treatments.

• 1:24:12Rangan Chatterjee?

  I would argue that that goes beyond mental health problems and actually that's kind of rationale is what we should be applying more to all chronic disease. I believe that from what I've seen and from the research I've read, that chronic illness, and I put mental health within that, so non-acute things like a heart attack or a chest infection, for example, these sort of more long-term symptoms and afflictions, there's very rarely in my experience only one cause, there's multiple things. So I could have 10 patients with a headache and they could have 10 different contributing factors.

• 1:24:53Rangan Chatterjee?

  The end symptom is the head hurts, but depending on what the cause is, the treatment's going to be different. And so, you know, we said earlier on about all these different things that, you know, our genetics, our social world, our diet, our physical conditions, like depending on what's driving the end products of low mood and anhedonia in the brain, well, the treatment's then going to be different depending on what the cause is, right?

• 1:25:21Speaker 00

  Exactly. Which is to say that, you know, that the train intervention that worked so well for that person who needed one source of kind of motivation, one source perhaps of pleasure, might not have worked for someone else for whom their kind of contributing factors for depression were just different.

• 1:25:39Rangan Chatterjee?

  Yeah, exactly. Okay, so in terms of some of these treatments then, people are familiar with the term antidepressants. One of the most common ones are SSRIs, selective serotonin reuptake inhibitors. In your view, do they work? And if so, how?

• 1:26:00Speaker 00

  In my view, SSRIs work in the old definition of the term, which is to say they work, you know, mostly, they work more than placebo for a large group of people. But that doesn't mean that they work for everyone. And I think to understand why, we need to understand how they work. There was a kind of old fashioned idea that came about through the discovery of SSRIs, that what SSRIs were doing was fixing a deficit of serotonin in the brain. Actually, in the beginning, it was serotonin, dopamine, and noradrenaline. And then they sort of modernized the drugs and modernized the explanation. And that's a compelling theory because it's so sensible.

• 1:26:44Speaker 00

  And it's how other disorders work, things like Parkinson's disease. It's a deficit of dopamine. You treat with the precursor to dopamine and then that remedies the symptoms. Unfortunately, it turns out depression is not so simple. So there is very mixed evidence to support a deficit of serotonin in the brains of people with depression. Some studies, but nothing kind of really definitive or convincing. The only thing I would say is convincing is that if people are on SSRIs and it's working, well, then if you deprive them of serotonin, you can give them a kind of really disgusting milkshake that depletes the amino acid precursor to serotonin, they get depressed again. So it is the route by which SSRIs are working when they're working,

• 1:27:30Speaker 00

  but it's not necessarily kind of how they work. They don't seem to be remediating a deficit in serotonin. So we've known this for at least a decade, probably more. But what they actually do, I think, is really interesting. And we might have to kind of think about the brain at a slightly different level than just these kind of, you know, general global levels of brain chemicals. So these were experiments done by Catherine Harmer and Phil Cowan in Oxford. And they discovered that while your mood doesn't improve from a single dose of SSRIs, one of the kind of conundrums is like, oh, it raises your serotonin right away. But then why doesn't it affect your mood right away? And it doesn't do nothing after that dose. It does something.

• 1:28:13Speaker 00

  What it does is it changes your perception of the world around you. It almost shifts your perception in a more positively valenced direction. So ambiguous things that happen to you, ambiguous information that you see in the world around you, you know, a colleague ignoring you in the corridor. An email with a title that could be like quite foreboding, but could also mean nothing. Your interpretations become more neutral or even more positive. Instead of having this kind of negative bias. That's very common in depression and other kind of related conditions. So by doing that, what antidepressants do is they enable you to experience the world in a slightly less negative way.

• 1:28:56Speaker 00

  And for people for whom this is the kind of core driver of their depression, they work. For people for whom changing this isn't a core driver, or even perhaps they don't quite change this in those people. Then I don't think they work.

• 1:29:12Rangan Chatterjee?

  And so let's say that is one of the main mechanisms by which these SSRIs work when they do work. And there's a lot of patients who they don't work for. That's for sure. I mean, there's there's different rates if you look at the published studies. And I don't know if you know the latest stats on that or not, in terms of how many people they work for.

• 1:29:32Speaker 00

  I often say 40%, but they don't work for. So 60% they do work for, but even that 60% often involves trying kind of more, more than one version. And, you know, so that it could even be, it could turn out to be about 50 50 when you turn up to your GP.

• 1:29:47Rangan Chatterjee?

  Yeah. So given the potential side effects of these SSRIs, of which there are many, including suicidal ideation, you know, it's published as a rare side effect. But nonetheless, it's, it is a well-recognized side effect.

• 1:30:02Speaker 00

  Yeah, and a really important one, obviously.

• 1:30:04Rangan Chatterjee?

  Yeah. So if the mechanism by which they work is they help to change our perception of the world. Could one argue, well, you can change your perception of the world in a variety of different ways. You could perhaps see a therapist or do CBT or do some other exercises that can help you reframe and look at the world differently. Without all the potential negative side effects.

• 1:30:31Speaker 00

  So I think yes and no. There are some things that SSRIs do that I think are quite difficult to do intentionally. So what psychological therapy can definitely does help you do is it can help you engage with the world more, it can help you reevaluate where your beliefs about the world come from. But actually, if your everyday life experiences and you know, the kind of mass of interpretations that you have of everything that's happened in your day, in your past, in tomorrow, if all of that, the bulk of that information disagrees with what your therapist is telling you, with what you're working on therapeutically, then there may be a point at which to access

• 1:31:13Speaker 00

  the benefits of that therapy or other interventions, changing that underlying perception could be critical. So for some people, therapy works after they've taken a drug or while they're taking a drug. That doesn't mean that antidepressants do something completely unique that nothing else can do. It might just mean that for some people, they are a kind of slightly unique pathway towards accessing those other interventions.

• 1:31:39Rangan Chatterjee?

  Yeah, on that theme of taking something that then perhaps changes or gets or helps jolt us out of our current viewpoint and helps us see the world through different eyes, that's something that people who take psychedelics will often report, and you do cover this in the book. What do you think about psychedelic therapy? And I know you've got some interesting thoughts on placebo and the placebo response and psychedelics.

• 1:32:10Speaker 00

  So on the kind of pro side, I think psychedelics can work in this kind of rapid way that antidepressants don't, but they might work on more similar systems to something like therapy. Things like your beliefs about the world around you, your beliefs about yourself. These seem to be able to be modulated by even like a single dose of some psychedelic drugs. And the research supporting that goes. Goes back many, many, many decades. But I do have one kind of really big pause when it comes to psychedelics. I very much support research in that area. I think it's been kind of suppressed for far too long. They certainly show potential.

• 1:32:51Speaker 00

  But my biggest worry is that so many of the big trials, trials showing like huge effects of what a psychedelic like psilocybin, active ingredient in magic mushrooms could do for depression are impossible, impossible to dissociate from the placebo effect. Because when you take a psychedelic, you know that you're taking a psychedelic. You just do. And the problem is the placebo effect is so powerful. And people probably underestimate just how powerful it is. It's even dependent on what you think the drug you're taking. So when you think you're taking a painkiller, and it's say, a sugar pill, your, the brain

• 1:33:33Speaker 00

  networks changed by that are different than when you think you're taking an antidepressant. But it's a sugar pill. So it's not like you just get sugar pill brain networks. You get what you expect. So in psychedelic drug trials, because almost all of them have this problem where people can tell they're taking a psychedelic and they've also been reading everywhere in the news about how great psychedelics are for mental health. It's really difficult to pull apart how much is placebo and how much is a true effect. There are ways to combat this. So there is another kind of class of drugs, so ketamine, which is not a classic psychedelic. In those trials, for a long time, they've been using as their placebo condition, a

• 1:34:16Speaker 00

  drug that also causes like somewhat similar effects. So if you're kind of drug naive, you haven't taken ketamine before, you could easily be fooled by midazolam, which is their control condition.

• 1:34:27Rangan Chatterjee?

  What did that show?

• 1:34:28Speaker 00

  And those, oh, those studies are generally quite positive, but they

• 1:34:32Rangan Chatterjee?

  For ketamine?

• 1:34:32Speaker 00

  For ketamine, but they reduced in the kind of size of the effect dramatically when they started using this good placebo. So I think that's what we'll see in psychedelics. Not necessarily that the effect just goes away entirely, but that it's actually more subtle, probably more variable between people than what it looks like right now.

• 1:34:51Rangan Chatterjee?

  And for people who don't know these terms psychedelics, ketamine, psilocybin, can you just break it down simply? Because I think there's people who, you know, read all this stuff and are very familiar what those things are, but there's other people who just wanna improve their mental wellbeing. They're hearing a little bit about psychedelics, go, well, you know, are they all the same? What's the difference between ketamine and psilocybin? So if you could just walk us through how to think about them.

• 1:35:15Speaker 00

  Yeah.

• 1:35:15Rangan Chatterjee?

  That would be helpful, I think.

• 1:35:17Speaker 00

  I mean, it's been a really interesting trajectory, actually. You know, when I started my PhD, drugs like psilocybin, active ingredient of magic mushrooms, classic psychedelic, another one would be LSD, these were drugs that people had used in scientific trials in the 1970s and earlier, but were really kind of out of fashion, you might say, but more than fashion, also kind of for legal reasons, for political reasons, very, very difficult to access for even totally scientific, robust trials and experiments. But there were some groups who'd started working on them at that time, and those groups have truly been proven right, I think, in their kind of radicalism at the time, because these

• 1:36:02Speaker 00

  drugs that had been neglected scientifically, clinically, by the establishment, if you will, actually seemed to have some kind of clinical potential, possibly for a wide range of conditions. Doesn't mean they're without side effects. So you mentioned antidepressant side effects. Psychedelics have side effects, too. Some people have really bad reactions to them. But it does mean they might hold promise. And you've seen a lot of excitement about that. Now, kind of in between falls drugs like ketamine. It's a dissociative drug. It's like an anesthetic, but it's not a classic psychedelic. It doesn't cause kind of hallucinations, or it also doesn't have the kind of drug properties that we

• 1:36:44Speaker 00

  associate with psychedelics. And that earlier had been shown to cause a rapid remission of depression symptoms. And today, there are ketamine clinics, including on the NHS, at least one I know of in the UK. So this is a kind of special way of treating depression for people for whom nothing else has worked. This anesthetic drug can sometimes deliver really rapid relief of symptoms.

• 1:37:12Rangan Chatterjee?

  Via this mechanism of resetting of view of the world and, you know, our perceptions.

• 1:37:20Speaker 00

  Well, that was my kind of hypothesized mechanism for psychedelics. I actually am not sure that ketamine works the same way. It could work a little bit. I know there's some data suggesting it might work a little bit on the kind of motivational side of things that we were discussing. But there's also, pharmacologically, it's so different than SSRIs. It's very different from psychedelics. It may have something to do with neuroplasticity mechanisms. It seems to work on things related to that. But who knows, really? We don't have a solid answer.

• 1:37:49Rangan Chatterjee?

  Yeah, it's fascinating, this whole idea of the placebo effect. And again, you really delve in detail in your book on the placebo effects and just how powerful it is. And I for many years have thought, we've looked down on the placebo effects. We've almost been a bit derogatory about it, but I think we should be harnessing it again. No, no, the placebo effect is really, really powerful. Some people may be thinking, well, yeah, I get it for drug trials or when you're taking a medication, but come on, Camilla, for a psychedelic, surely you're gonna know because you're not gonna get all of those wild experiences when you're taking the placebo. But you're writing, actually, that some people do get fooled.

• 1:38:32Speaker 00

  Yeah, exactly. So this just shows just how powerful expectations can be. So I said that in psychedelic trials, the placebo condition does feel very, very different than the psychedelic condition. So people can tell. But actually, in other studies, if you only give people a placebo, but you really big it up, you say like, this is a new psychedelic that we've discovered, it's gonna make you feel this and that, it's gonna feel a little bit like magic mushrooms. A good proportion of people, not everyone, but over 50%, experience some kind of psychedelic-like effect. Oh, I loved reading that study. There was even one participant in it who loved it so much, they didn't believe it when they were told it was a placebo.

• 1:39:14Speaker 00

  And they said, you've got to help me get my hands on this placebo again, then.

• 1:39:19Rangan Chatterjee?

  My God. So that's how powerful the placebo is. And why do you think the placebo is that powerful?

• 1:39:27Speaker 00

  I think it has to do with the strength of the role of expectations in the brain. So we talked a little bit how pain can be dampened up or amplified by brain mechanisms. And that's, you know, one thing that the placebo effect is an example of. It's an example of how your brain can kind of turn that dial up and down. But it's not just on pain, it's on everything. So what we expect to see constrains our visual perception of the world. That's what causes visual illusions, is essentially a kind of visual placebo effect, a visual effect of our expectations. But of course, our senses are not just seeing.

• 1:40:08Speaker 00

  So what we feel in the body emotionally and physically is also subject to our expectations. So that is the route by which the placebo effect can change things all over the body. You even see differences in the spinal cord when people take a placebo. So it's not just in the brain, which then transmits signals to the body in the spinal cord. You can even see literally differences in the spinal cord.

• 1:40:33Rangan Chatterjee?

  Yeah, it's absolutely incredible. But then when you think about placebo, it goes so much further than this. Because let's say with talk therapies, for example, or therapy,

• 1:40:44Rangan Chatterjee?

  we know that actually your relationship with the therapist is very, very important in terms of whether that therapy is going to work and it's going to be effective for you. You know, that patient with the toy train set,

• 1:41:03Rangan Chatterjee?

  I have to acknowledge that my interaction with that patient, my belief and what I said to that patient about hobbies and how important pleasure was going to be for their mental wellbeing. And give this a go, I honestly think it's going to help you. That is altering his expectation because then when he's going up the ladder to his attic that evening, if I had a good rapport with him, which I did, and I'm, I as a clinician have always tried to be very empowering to make sure people walk out the door feeling, oh, there's something I can do about this. Well, that's also going to play a role, isn't it? It's not just the train set, it's the idea I put in his brain about what that train set may or may not do.

• 1:41:46Speaker 00

  Exactly. This is a problem, actually, for kind of psychological therapy trials and really sort of developing and honing new therapies. It will always be influenced by the therapist themselves. But there's an optimistic side of that as well, which is that if you're like, oh, I've tried CBT before, it was crap, it didn't work for me, might have actually been your particular relationship with that therapist and you might, you could try again and it could be slightly different.

• 1:42:10Rangan Chatterjee?

  The flip side is, um, let's take back pain. Back pain is a leading cause of disability around the globe. We've covered this a little bit on the podcast with Howard Schubiner and this amazing physiotherapist from Australia, Peter O'Sullivan. And just sort of piggybacking off what we're talking about, expectation and the placebo response. If you are, let's say 35 and you've got backache and then your doctor scans your spine, let's say they send you for an MRI. The way we report those MRIs is actually potentially very, very problematic.

• 1:42:50Rangan Chatterjee?

  So it's very common to say degenerative disc disease, which frankly is a normal finding. But if you think about that language, degenerative disc disease, who wants to be told that they've got degeneration in their spine, right? So you're then this kind of fit 35 year old patient who has got back pain, you know, you don't think it's serious, but it's really bothering you. After a few months of trying things aren't working, you persuade the doctor to send you for an MRI scan. The doctor goes, oh, there's nothing serious. You know, and you see the result and you read a degenerative spine. What does that then do to your perception of your movement, your pain? I think it's massive.

• 1:43:34Speaker 00

  Yeah, I think so too.

• 1:43:35Rangan Chatterjee?

  I think it's absolutely huge. And I don't think as doctors, we, I don't think we've been educated enough into how we communicate with our patients. If the placebo effect is as powerful as you're saying, and I believe it to be. Actually, the way we communicate anything to our patients is of the utmost importance.

• 1:43:56Speaker 00

  It absolutely is. I even know of trials testing this directly where the same intervention, because even treatments, kind of normal biological treatments, they partially work from a placebo effect. So actually, they could be boosted potentially by the kind of communication that you're talking about. So I think in these trials, they're tweaking like what exactly patients get given in manuals, but also probably what the clinicians say to them. So they're tweaking just expectations.

• 1:44:24Rangan Chatterjee?

  Yeah, so just as 10 people with depression could have 10 different driving factors that's causing their depression, which might mean they all need subtly different treatments, right? It also makes you think then, as a clinician, and there's loads of doctors who listen to this show, pharmacists, nurses, physiotherapists, right, and osteopaths and beyond, actually, when we think about the tools that we have in our toolbox to help a given patient, we probably need to upgrade our view of our manner, our emotional state. How are we, you know, how much are we smiling? How much are we being positive

• 1:45:06Rangan Chatterjee?

  and empowering, right? It's not just about the blood test and then the prescription we can write. It's the way we write it, the way we communicate also has to be upgraded to be thought of, I would say, at a similar level.

• 1:45:20Speaker 00

  I think so. And I think it actually, it explains a really interesting phenomenon in medicine, and this is kind of outside of mental health. But if you look at many disorders, things like multiple sclerosis, stroke, ideas where you have exactly, you have a good prediction of how disabled someone should be based on their pathology. Actually, it corresponds poorly. There's a relationship.

• 1:45:46Rangan Chatterjee?

  Yeah.

• 1:45:47Speaker 00

  But it doesn't account for all the variability in how disabled someone is by their specific lesion, by their specific degeneration. And in my opinion, that's at least partially because of this interceptive sense that we have, the perception of the internal state of the body, which is powerfully modulated by expectations, of course, because that's how we know what to attend to, what's important, what's meaningful, what's negative, what's positive. And that is the bit that I think clinicians are working on in this manner, in this relationship that you're talking about. It's changing the way you interpret your symptoms.

• 1:46:28Rangan Chatterjee?

  I want to talk about interreception. And this idea that our expectations or our understanding of the world alters the way we interpret that symptom. So a very simple example might be,

• 1:46:45Rangan Chatterjee?

  and actually, this is hypothesized to be one of the reasons why exercise is so good for us is because it enhances our interreception. Right, that's, I don't know if you've seen that research. Certainly, I find that fascinating. This idea that if you don't move your body regularly or you don't move it much at all, if you have an elevated heart rate, for whatever reason,

• 1:47:06Rangan Chatterjee?

  it may not feel good. You may think, what's going on? Am I sick? You know, you start to feel anxious, right?

• 1:47:11Speaker 00

  Exactly.

• 1:47:12Rangan Chatterjee?

  But if you're running on a treadmill in the gym, your heart rate's going up, but you associate it positively. It's, oh, yeah, my heart rate's up. Like, yeah, I'm working my body, I'm moving it. So maybe not quite the same thing's happening, but you're, from an increased heart rate, you're interpreting it in two completely different ways because of your perception. So what is interreception? How is it related to our mental health?

• 1:47:40Rangan Chatterjee?

  And what can we do to improve it?

• 1:47:42Speaker 00

  Interception is the sense of the internal condition of the body. So extraception is the sense of the outside world. So hearing is an example of extraception. Seeing, even tasting, is an extracceptive sense because you're tasting something you put on the tongue. But as soon as something is inside our body, whether that is our heart beating or something we've eaten that we're digesting or our bladder, these are all sending signals up through the brainstem into the brain and we're processing these signals all the time, like a cacophony of signals. And that is interception. But interception is more than just listening to the body. It actually is predicting what the body will feel, processing those signals

• 1:48:27Speaker 00

  with knowledge of how the body has felt in the past and what those signals have meant. So that's how we can predict, you know, if we're about to get ill. So we're interpreting even things like inflammation in the body, a very generic sense of all around us. We're interpreting that with meaning. We might interpret those same signals slightly differently. I don't know if we just run a marathon. So you might say, oh, I'm not getting ill. I just, my body feels this way because I've just run a marathon. But I think in your example of how important interception is and why exercise might help kind of harness that interception, there is an additional thing happening. Yes, you get a new context for an increased heart rate. It's not necessarily bad.

• 1:49:12Speaker 00

  It's not necessarily anxiety, fear or a heart attack. It's something, maybe something good. But you also often get the ability to control that signal. So as you exercise, you experience these heightened physiological signals and you also the experience the ability to maybe slow your breathing, maybe slow your pace. And actually you discover that you have probably better control of your bodily signals than someone who's experiencing that increased heart rate purely as a reactive signal to the world around them.

• 1:49:44Rangan Chatterjee?

  So do we know from the research that people who struggle with their mental health have?

• 1:49:52Rangan Chatterjee?

  Poorer levels of interception, does that, does that make sense? Can you even say poorer levels?

• 1:49:57Speaker 00

  Yeah, so there is a general decrease in your accuracy of interception in a number of mental health conditions. So that might mean, for example, that you're slightly less good at telling when your heart beats. Or you can do this in breathing as well. So some of the experiments in my lab, we restrict people's breathing very subtly and we ask them when they can feel it. So people might be slightly less kind of able to detect these subtle differences. But to be honest, I think that's actually just one end of the spectrum. I think some people have very, very good interception and that's not necessarily for benefit. So I think if you have a really kind of harnessed sense of your body,

• 1:50:40Speaker 00

  but perhaps something awry in your interpretation of that body. So you might be perfectly able to detect your heartbeats and other symptoms from the body, but your interpretation still might be somehow dysfunctional. That is also an interceptive problem, but it's not necessarily good or bad interception. It's at that other level, at that interpretative level.

• 1:51:03Rangan Chatterjee?

  Yeah, it reminds me of a conversation I had a couple of years ago with this wonderful chap who runs a company called Physiology First in America. And he basically trains children and teenagers, adolescents. He gets them in saunas, cold plunges, he gets them on exercise bikes, he teaches them breathing techniques. And one of the things he tries to do is teach these teenagers what an increased heart rate feels like and how you can control it. And then teach them how with their breathing, they can control their sensation of pain and discomfort. And I guess one of the things he must be doing is helping them.

• 1:51:48Rangan Chatterjee?

  With that interoception.

• 1:51:49Speaker 00

  I think that's exactly right. He's essentially doing a kind of interceptive training where very kind of old psychological therapy, they might have exposed someone with panic disorders to carbon dioxide inhalation, because that's what happens when you're having a panic attack. And if you experience it and you learn to kind of control it and control your breathing, control your response to it, that can kind of stop a panic attack in its tracks. But you have to train for it. So that's what I think he's doing.

• 1:52:18Rangan Chatterjee?

  Yeah. And incredibly, since that podcast, he got contacted by so many people in the UK. He's actually opened up his first centre in the UK in Sale, which is not far from here. And he's pretty incredible what he's trying to do. And I think it's, some of it at least is via this interoception mechanism. Given what you know about interoception, and people want to learn more, there's a whole chapter on interoception in The Balanced Brain.

• 1:52:44Rangan Chatterjee?

  What's your take on

• 1:52:47Rangan Chatterjee?

  certain practices that can

• 1:52:52Rangan Chatterjee?

  perhaps train us in interoception? So body scans, meditation, yoga, I believe you're a keen practitioner of yoga.

• 1:53:02Rangan Chatterjee?

  Do you think those things are generally helpful for most people as a way of improving their mental health?

• 1:53:09Speaker 00

  I do. So we're actually running a big study at the moment, looking at whether interoception is the crucial bit of mindfulness-based therapies that makes them work for anxiety and depression. So we're very lucky that Welcome invested in this long-term study to look at whether or not interoception is kind of the key of this intervention. And if it is, which we think it might be, then actually boosting interoception via very simple things like training people to attend to their heartbeat could actually help things that we already know work for many people, like mindfulness-based therapies. But I also think kind of outside the maybe more clinical realm, that other things also affect interoception.

• 1:53:50Speaker 00

  So I don't even think I'd heard of interoception when I started practicing yoga regularly, but it really had a Profound effect on my interpretation of signals from my body. Partially because when I started, I was practicing hot yoga. So it's really, it's like incredibly hot. You're sweating buckets and your heart is going out of control. You really feel like you might pass out. And I'd actually, as a teenager, I'd had a couple of panic attacks, which were really scary. I didn't know what they were. And then in my kind of early twenties, late teens, early twenties, I started doing hot yoga. And I realized I felt just like those panic attacks, but I never passed out. Actually, I could kind of keep going and it wasn't the end of the world.

• 1:54:34Speaker 00

  And it actually wasn't necessarily negative. It was kind of a cool thing that I could overcome. So I really feel that was a sort of interceptive training that I experienced. In that case, it was a kind of interceptive interpretation training, but also probably control. Because one of the things yoga teaches you is how to control your breathing and so on.

• 1:54:51Rangan Chatterjee?

  Yeah, there's, there's just, it's so fascinating, interception, that sixth sense that maybe many of us have lost touch with. And there's some really good studies that I've seen on drug and alcohol addicts. And I think those who were trained to increase their interception through, I think mindful breathing practices, reduced their rates of relapse and reduced their rates of depression as well, which is pretty remarkable. So I think interception is something that's very, very important. One thing I think a lot about is this idea that these days we've lost the art of paying attention to our internal signals and our bodies.

• 1:55:36Rangan Chatterjee?

  I think one of the reasons is because it's never been easier to distract ourselves, right? So it's easy now to wake up in the morning. And instead of paying attention to anything internal and in terms of how you're feeling, your mood, your heart rate, your breathing, any tightness, we can distract straight away on these devices, emails, podcasts, music, news, whatever it is. So my feeling is that we're constantly out there in the world, you know? So I, I often say that even if you're consuming really good content, like I hope this podcast is for people.

• 1:56:14Speaker 00

  Like a podcast, yeah.

• 1:56:15Rangan Chatterjee?

  Even if you're doing that, if you're doing that all the time and you're not having any time to listen to yourself, I think that's a problem. You're a neuroscientist at Cambridge. What's your take on that?

• 1:56:30Speaker 00

  I think people fall on that end of the spectrum more and more, perhaps. The end of the spectrum where actually a deficit in interpreting internal signals of the body can get you to a really dysfunctional place. That might mean a place that leads to anxiety or interpreting sort of physiological signals of anxiety kind of hyperactively. But it also, you know, we interpret these physical signals constantly to suggest really critical things like, should we eat? Are we full? These are signals that end up having huge repercussions for our physical health, but they depend on our interceptive ability.

• 1:57:10Speaker 00

  So if you're someone who isn't really listening to hunger or fullness, well, you might well not be eating when you should, how much you should, and so on.

• 1:57:19Rangan Chatterjee?

  Yeah, and you talk about that in the book, don't you, about being hangry, right? So let's talk about being hangry because it's something I think many people experience. And that is, in some ways, I think, interception gone wrong?

• 1:57:33Speaker 00

  Yeah, or right. It's the nature of interception is that we use the insula, a region in the brain that helps us interpret signals from the body, also to tell us what we're feeling. So that means that signals from the body are one way of telling us our emotions. And so the very same signals that are telling us that we're hungry could actually, in another context, have been telling us that we're distressed. So this region is saying there's this homeostatic disruption, this disruption to the balance of my body. And actually, that could have been because of some kind of emotional disruption.

• 1:58:13Rangan Chatterjee?

  So when someone feels hangry, so, you know, for people who don't know that term, you actually are hungry. Your body wants food and, let's say, needs food, but you don't know that.

• 1:58:26Speaker 00

  That's right. You don't know it yet.

• 1:58:27Rangan Chatterjee?

  And so you're moody and you're angry, hence hangry. But you don't realise that actually it's not really anger. Well, I guess it is, but actually, your mood is because you haven't eaten.

• 1:58:42Rangan Chatterjee?

  I'm saying that's interoception gone wrong. You're saying it could be that it's gone right. Can we just tease that out because it's fascinating that?

• 1:58:48Speaker 00

  So what I'll say about hangry is that actually not everyone feels anger. It's often closer to irritability. Maybe you feel easily frustrated by things. Maybe you actually just feel kind of quite emotional or sad. So these are all things that you can kind of mistakenly interpret the symptoms of hunger for. And the reason for that is that the way you interpret hunger, the signals that are sent to the brain, the way the brain interprets that is actually very similar to the way the brain interprets how it's feeling emotionally. So if I ask you how you're feeling emotionally, you're using these interoceptive senses to listen to your body. So that's the way that it's going right.

• 1:59:31Speaker 00

  Because if you were to say, well, right now I'm feeling a bit anxious, you would have been listening, using your brain to listen to your heart, to maybe your muscle tone, it's feeling very tense right now. So that will have been what the brain is doing to tell you how you feel. Or disgust, one of my favorite emotions, actually, not to experience, but to experiment with. That involves signals being sent from the stomach. So the brain, to interpret something as disgusting, part of what it's doing is it's listening to the stomach.

• 2:00:06Rangan Chatterjee?

  For someone who then experiences hunger regularly, who ends up in a situation where they feel irritable, frustrated, moody, whatever it is, whereas actually it's, let's say their blood sugar's dropping a little bit and they actually need to eat.

• 2:00:26Rangan Chatterjee?

  Can they retrain that so enhance their interoceptive ability to detect what's going on and how do they do that?

• 2:00:35Speaker 00

  I definitely think people can get better at detecting the sort of true source of hunger. Some of it is with sort of knowing it's been a kind of certain amount of time since your last meal, but some of it is probably through getting slightly better at detecting the sort of subtle physiological difference. Between feeling hunger and feeling irritable. For example, in this case, also the involvement of the stomach. So if you feel angry and irritable, but you're good at telling my stomach is quite empty right now. It's maybe rumbling a little bit. That's going to help you tell you the source of those feelings and that the source is hunger and not, in fact, your emotions.

• 2:01:13Rangan Chatterjee?

  Yeah, you're studying interception a lot, so I'm going to, again, put something else to you, which I've discovered.

• 2:01:20Rangan Chatterjee?

  Health trackers and wearables, okay? So I don't think they're for everyone. I think some people can have quite a dysfunctional relationship with them, become anxious. Every little figure that goes slightly wrong, it can stress them out. I definitely think that is real and people can become so dependent on them that they can't function without them. At the same time, I think there are some people who thrive wearing health trackers and health wearables. So let's take a CGM, for example, so continuous glucose monitor that traditionally has only been used for people with type one and type two diabetes. More commonly now in health and wellness, some people are using it to help them understand how they respond to different foods.

• 2:02:04Rangan Chatterjee?

  Now, what I've seen with some patients and what I've experienced myself is that wearing a CGM now and again actually can help you with your interreception because you start to then go, oh, wow. Oh, I can see that the sugar's dropping there and that correlates when I feel tired and a bit low. And again, to be really clear, I think things can be overused, but I think if they're used intentionally and carefully, I believe that they can enhance your interreception and your ability to detect what's going on. I've been experimenting with this whoop band for a few months.

• 2:02:46Rangan Chatterjee?

  I spoke to Kristen Holmes, the chief scientific officer there a few months ago, had a great conversation with her on the show. And I thought, yeah, you know what, let me try this. It's been really fun for me, and I can't say that's for everyone, but for me, I feel I understand my body's signals now much better than before using this. So heart rate variability, this marker of the state of my nervous system essentially, and how much stress it is under, how well recovered it is. I am starting to pick up now, like I can predict quite nicely, not 100% of the time, but I would say, I'd probably say 90, 95% of the time, I can predict roughly where my HRV is going to sit because of what I've learnt.

• 2:03:31Speaker 00

  That's very cool. You've done essentially some kind of biofeedback training on yourself where you've like begun to tell what the signals are that are leading something to respond in that way. I love that. Also, I love the example of the CGM, something that people, you know, has a clear medical purpose, but has also kind of given you information that you use crucially when you're not even wearing a CGM. So you kind of learned what it feels like, thanks to the CGM, which is very cool.

• 2:03:56Rangan Chatterjee?

  Yeah. So anyway, maybe that can factor into some of your research in the, in the coming years. Cause I'm always thinking, well, how do you help people with their interreception? Wearables are here and they're here to stay. I don't think they're necessarily for everyone, as I say, but I think for some people, if you're quite intentional, I think they can be pretty profound. So, you know, let's see where that field goes.

• 2:04:16Speaker 00

  I also think it depends what information your wearable gives you. So we were having a chat in my lab the other day about if your wearable gives you kind of like maybe more negative information, it says like, oh, you had a really bad quality sleep last night, sometimes even more than you would have perceived. That actually could have negative repercussions. So you might want your wearable to be like a little bit biased positively.

• 2:04:37Rangan Chatterjee?

  That, that study's been done, actually. There was one study where they, they took people, well, there's been multiple studies on this, they took people into a lab. And I think from recollection, one half, one group was slept for five hours. The other group was slept for eight hours. But then the group who slept for eight hours, they told had only slept for five hours and vice versa. And you could actually see a difference later on in the day in their subjective feelings. And I think some physiological findings, which again speaks to what you've been saying about the placebo response and how powerful our mind is and our expectation.

• 2:05:15Speaker 00

  I'm slightly annoyed that someone else has already done that experiment because I wanted to, but that is really cool.

• 2:05:20Rangan Chatterjee?

  Well, do it. Repeat it. I'm gonna share. I'll share you the link to that so you can see it. But maybe you can repeat it. I think it'll be fascinating, that sort of stuff.

• 2:05:27Speaker 00

  Yeah.

• 2:05:27Rangan Chatterjee?

  Okay, just before we got into the studio, you were talking to me about some new things that you've been really excited about recently. Metabolism and our mental health. Can you share anything about that?

• 2:05:38Speaker 00

  Yeah, my lab has taken this like slightly surprising turn recently because we've become interested in, we've always been interested in kind of signals from the gut. But actually, the signals that we get from the gut are very complex. It's not kind of, there's, you know, some electrical signals that you get just from the contraction of the stomach, which we've studied before. These are the signals that are involved in things like disgust, nausea, fullness. But actually, another kind of signal that we get are the sorts of signals we get eventually from the gut, from the things that we eat, that then get transmitted to the kind of large metabolic system all over our body.

• 2:06:19Speaker 00

  And what we found is that there may be interesting consequences of having metabolic differences in the body. So as people, we looked at people's kind of diabetes risk score across people with and without diabetes. And we found that people with a higher risk for diabetes and then people with type 2 diabetes show differences in that effort cost decision making that I was discussing. So there's actually a kind of a bias towards conserving energy in people with, you might think, worse metabolic health. So the kind of, the better your metabolic state, the more likely you are to engage in effortful behavior that involves some kind of effort cost.

• 2:07:02Speaker 00

  So just quite interesting, a sort of brain implication of your metabolic health.

• 2:07:06Rangan Chatterjee?

  Yeah, and I guess if we think about that theme of bi-directional communication. Do we know which one comes first?

• 2:07:13Speaker 00

  No, we don't. So I think it's totally plausible that these might be natural brain differences in the population that lead us to behave differently, eat differently, exercise differently, and then that leads to metabolic consequences.

• 2:07:26Rangan Chatterjee?

  Yeah, it's absolutely fascinating. Wow. I mean, look, Camilla, there's just so much in your book we haven't even got to yet. And I don't think we'll have time in this conversation. I'm sure there's an Afro part two at some point later on in the year. We were talking about drugs before. One drug we didn't mention was cannabis. And I think it's worth just pausing on that for a moment because there's a lot of people out there who are smoking weed. I know a lot of parents are concerned with how much their children or their teenagers are smoking weed and cannabis. What is the latest research saying about the effects

• 2:08:08Rangan Chatterjee?

  of cannabis on our brain and our risk of mental health problems?

• 2:08:13Speaker 00

  I think it's such a relevant question because more and more places are legalizing cannabis. And what consequences will that have on health? I think in some ways, we don't entirely know. What we do know is that there are kind of quite important chemical differences between the cannabis that people are smoking today and the cannabis that people were smoking several decades ago. And that has to do with the constituent parts. THC versus cannabidiol, which are the two chemicals that people focus on in cannabis, have a particular ratio. And as time has gone on, the ratio of THC has gone up relative to

• 2:08:55Speaker 00

  cannabidiol. And this seems quite important when it comes to abuse of cannabis, but also possibly side effects. So I even know of a clinical trial treating cannabis dependence with cannabidiol. So with one of the ingredients. And so that's how significant these two constituent parts are.

• 2:09:19Rangan Chatterjee?

  People have heard of CBD.

• 2:09:20Speaker 00

  CBD, yeah, sorry. I should have said that.

• 2:09:21Rangan Chatterjee?

  No, no, I'm just trying to make sure people are following along in the sense of cannabis is shortened to CBD because I think people are seeing that that's coming out more and more for pain and and other reasons. So you're saying the balance has changed over time. So colloquially, the weed of the 1960s is not the same as the weed of 2025.

• 2:09:42Speaker 00

  Yeah, totally. But what can this tell us? It's not just a bad thing. It could actually help us understand how even the same drug could be more negative or more positive depending on how it's made. So in places like states in the US that have legal cannabis, they should be using this information to inform sort of what kind of cannabis is legal. I don't know if they are, but that would be sort of one thing I would do based on that line of research. And I think the other thing to bear in mind about the risks of cannabis, of which there are definitely some and they're worth talking about, is that sometimes those risks should be looked at relative to other legal drugs like alcohol.

• 2:10:24Rangan Chatterjee?

  Yeah.

• 2:10:24Speaker 00

  So alcohol is actually quite a dangerous drug. And just because it's legal, people sort of neglect that. And I suppose in my book, I could be accused of being a bit like pro recreational drugs, but that's only relative to alcohol.

• 2:10:38Rangan Chatterjee?

  Yeah.

• 2:10:39Speaker 00

  So if we have a standard of legality with alcohol, I think we need to kind of change which other drugs are legal. And I, my hope would actually be that this would reduce people's consumption of alcohol, which can have really long term negative consequences, but also immediate negative consequences on health.

• 2:10:57Rangan Chatterjee?

  Yeah. I don't think you could be accused of that. I see what you're saying. I think you've managed that chat so really well. And, you know, you mentioned Professor David Nutt, who I hope to speak to later this year on the, on the podcast. And in terms of his views on drugs and alcohol and how we, we've kind of got a bit messed up with how we've classified these things legally and, you know, alcohol really is, it has a huge potential for harm, yet it's legal. Um.

• 2:11:24Rangan Chatterjee?

  Given what you've said about cannabis, and then obviously the logical line from that is when we talk about cannabis and its impact on the brain and mental health, we can't really, because we have to specify, well, what percentages are we talking about?

• 2:11:38Speaker 00

  Yeah, true.

• 2:11:39Rangan Chatterjee?

  Because actually, that balance is going to have a different effect. Understanding and acknowledging that complexity, are you able to give a more broader guidance for anyone who's concerned either with their own cannabis intake, or their children's, or family members, for example, of which I know there are many? Are you able to sort of give a general take on what you think regular smoking of cannabis is doing to our risk of mental health problems? Or is it too hard to say?

• 2:12:11Speaker 00

  No, it depends. I cannot say completely blanket, but there are some very interesting possible risks, especially depending on the age that you smoke cannabis. So people have for a long time, and I'm sure many of your listeners will be aware, that there is a relationship between smoking cannabis and development of symptoms associated with schizophrenia, like psychosis. So this is a really important association to understand. But the association does actually run in both directions. So one of the reasons that correlation exists and is relatively strong is because if you have a genetic propensity for psychosis, you are more likely to smoke cannabis and

• 2:12:56Speaker 00

  to do it earlier than people without. So it does run in both directions, but if anything, it's kind of stronger in the if you have a risk for psychosis, you smoke cannabis direction. So it's not something worth neglecting, it's something worth bearing in mind when we talk about that association. I would also say dependence on lots of different substances is bad. It's not the substance itself necessarily, it's not like somehow being addicted to cannabis is worse than being addicted to alcohol, you could probably argue the other way around, but that actually if you feel you have a problem with functioning because of a substance, any substance, that's something you need to seek help for, you or a loved one.

• 2:13:35Rangan Chatterjee?

  Yeah, it's not the drug, it's your relationship to the drug.

• 2:13:38Speaker 00

  Yeah.

• 2:13:39Rangan Chatterjee?

  Yeah. Okay, look, we've covered so many different things, these kind of brain pathways of pleasure, pain, motivation and learning. We've covered this idea that there's no one size fits all. We've gone through various drug treatments, antidepressants, how they potentially might work, the power of the placebo response, interreception, you know, all the different causes. I mean, I think, I think we've covered a lot. Is there anything that we haven't covered that you think is really important for people to know?

• 2:14:09Speaker 00

  I suppose there is one thing we haven't talked about, probably because it's weird and many people won't have heard of it or thought about it in the context of mental health.

• 2:14:17Rangan Chatterjee?

  I'm excited already.

• 2:14:18Speaker 00

  Yeah, all right. And that's brain stimulation. So this is an area that I think emerges mired in controversy in mental health because people think of ECT, electroconvulsive therapy. But actually, the way that it's used today, very, very rarely is something like ECT used only in the most extreme cases and for them it is often effective. But for most people, they wouldn't be appropriate for ECT, but they might not be responding to other kinds of treatments. And that's where I think non-invasive brain stimulation approaches like transcranial magnetic stimulation or TMS hold really quite significant promise.

• 2:15:01Speaker 00

  There are now substantial studies, big meta-analyses, looking at all those studies' effects, showing that something like TMS has about the same effect as antidepressants, meaning it doesn't work for everyone, but it works for a large proportion of people for depression. And it feels like a sort of quite intense tapping on your head. What it does is it increases the activation of brain cells underneath where you're putting this, it's called a TMS coil. So it's a quite localized effect, although it also kind of changes the circuitry related to that location. And it sounds weird and sci-fi and so on, but what I can say is that I think the evidence is convincing enough that more people should know about it and be able to look into it and access it, should they not respond to other treatments.

• 2:15:46Rangan Chatterjee?

  And is this commonly available now with psychiatrists?

• 2:15:50Speaker 00

  I think not commonly available enough. So there are a small number of clinics, some NHS clinics, but at least in the UK, there really isn't widespread availability, despite kind of quite high efficacy rates.

• 2:16:04Rangan Chatterjee?

  Absolutely fascinating. If we were to have a conversation in 12 months, I'm fascinated to see where this field would have moved on, where all this research that your lab is doing and other labs are doing is going to be. Honestly, I think you've written a wonderful book. It's so rich in information. It's quite a unique take on various aspects of the brain, which really got me thinking. And I've tried to explore a lot of those ideas with you today. To finish off then, if anyone's listened to this conversation, Camilla, and is thinking, well, I need to, not I need to, I'd like to do a little bit more for my mental health, dare I say, my mental wellbeing.

• 2:16:49Rangan Chatterjee?

  With the understanding that everyone's different, do you have some general guidance for people, given that you're a neuroscientist and you've been in this field for a long, long time now?

• 2:17:01Speaker 00

  Yeah, I would tell you what I would do, which is, I think, one of the most important messages you can take from my book is not the sort of depressing generalization that nothing works for everyone, but actually that I think something works for everyone. And that something, I hope for you, it already exists. But it is possible that that is still in development, that we still need more science to discover that. But it's coming, it's coming quickly. There are huge resources dedicated to developing new innovative mental health treatments, working as we speak. So I think that kind of diversity of treatments is a good thing, as well as, you know, sometimes a bad thing.

• 2:17:43Rangan Chatterjee?

  Yeah, very empowering. And are there two or three kind of general

• 2:17:49Rangan Chatterjee?

  practices that you think, actually, whilst you can't say for sure this is going to work for you, these are generally good things to be doing? For your mental wellbeing and your physical wellbeing, I guess, from your research, you know, where would you go if you were going to recommend some general practices for people?

• 2:18:06Speaker 00

  Yeah, the two biggest things I would say, one is obvious, one is less obvious. So one is to focus as much as you can on things like sleep hygiene and also exercising, if you can. These sort of basic things can often be the difference between resilience in the face of great mental health challenges that we all sadly experience at some point in our life and not. So I think focusing on those kind of crucial fundamental aspects of health if you can. And then the second thing I would say is pleasure. Even if you feel that a life of austerity is like on a pinnacle, something we all need to be aspiring

• 2:18:47Speaker 00

  to, I think actually you need to look at what is pleasurable in your life and don't neglect it.

• 2:18:54Rangan Chatterjee?

  Yeah, I love it. Camilla, you're doing great work. Thank you for writing such a wonderful book and thank you for coming up to the studio. I can't wait for our next conversation.

• 2:19:03Speaker 00

  Oh, thank you so much for having me.

• 2:19:09Rangan Chatterjee?

  Really hope you enjoyed that conversation. Do think about one thing that you can take away and apply into your own life. And also have a think about one thing from this conversation that you can teach to somebody else. Remember, when you teach someone, it not only helps them, it also helps you learn and retain the information. Now, before you go, just wanted to let you know about Friday Five. It's my free weekly email containing five simple ideas to improve your health and happiness. In that email, I share exclusive insights that I do not share anywhere else, including health advice, how to manage your time better, interesting articles or videos that I've been consuming, and quotes that have caused

• 2:19:53Rangan Chatterjee?

  me to stop and reflect. And I have to say, in a world of endless emails, it really is delightful that many of you tell me it is one of the only weekly emails that you actively look forward to receiving. So if that sounds like something you would like To receive each and every Friday, you can sign up for free at drchatgy.com/friday5. Now, if you are new to my podcast, you may be interested to know that I have written five books that have been bestsellers all over the world, covering all kinds of different topics, happiness, food, stress, sleep, behaviour change and movement, weight loss and so much more. So please do take a moment to check them out. They are all available as

• 2:20:36Rangan Chatterjee?

  paperbacks, ebooks and as audiobooks, which I am narrating. If you enjoyed today's episode, it is always appreciated if you can take a moment to share the podcast with your friends and family, or leave a review on Apple Podcasts. Thank you so much for listening. Have a wonderful week. And please note that if you want to listen to this show without any adverts at all, that option is now available for a small monthly fee on Apple and on Android. All you have to do is click the link in the episode notes in your podcast app. And always remember, you are the architect of your own health. Making lifestyle change is always worth it. Because when you feel better, you live more.