Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Recently, the Huberman Lab podcast hosted a live event at the Sydney Opera House in Australia. The event was called the Brain Body Contract and featured a lecture followed by a question and answer session with the audience. We wanted to make the question and answer session available to everyone, regardless if you could attend. So what follows is the question and answer session from the Sydney Opera House in Australia. I also would like to thank the sponsors for the event. They are eight sleep and ag one. Eight sleep makes smart mattress covers with cooling, heating and sleep tracking capacity now, one of the key aspects to getting a great night's sleep is to control the temperature of your sleeping environment. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up in the morning feeling refreshed, your body temperature actually has to increase by about one to three degrees.

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The EU and Australia. Again, that's eightsleep.com huberman the other live event sponsor, ag one is a vitamin mineral probiotic drink that also contains adaptogens and other critical micronutrients. I've been taking ag one daily since 2012, so I'm delighted that they decided to sponsor the lab event. The reason I started taking it, and the reason I still take it every day, once or twice a day, is that it ensures that I meet all of my quotas for vitamins and minerals, and it ensures that I get enough prebiotic and probiotic to support gut health. Now, of course, I strive to consume healthy whole foods for the majority of my nutritional intake every single day. But there are a number of things in ag one, including specific micronutrients that are hard to get from whole foods, or at least in sufficient quantities. So ag one allows me to get the vitamins and minerals that I need. Probiotics, prebiotics, the adaptogens and critical micronutrients. To try ag one, go to drinkag one.com huberman and you'll get a year's supply of vitamin D, three k two and five free travel packs of ag one. Again, that's drinkag one.com huberman thank you to the Sydney Opera House for hosting us and for making this event possible.

What are the latest findings on the physiological mechanisms behind stress's impact on the body and brain? And what are some practical tools or techniques for managing stress effectively? Well, thank you for that question. I'll deliberately not repeat what I said earlier about physiological size, panoramic vision, etcetera, and raising stress threshold, because we covered that already. But I think that one of the most interesting findings, two most interesting findings in the field of stress in the last five years or even three years, I think the work from my colleague Allie Crum at Stanford, she's been a guest on the podcast. She works on mindsets, is the following result. Students, Stanford students, that is, come into the laboratory. They view a, I think it's a five minute movie about how awful stress is for the mind and body. All the things it does, like, deplete your immune system, make you miserable, deplete certain aspects of the reproductive axis and on and on. And then a separate group comes in and watches a video, also five minutes, also true about all the things that stress can do to enhance performance, both cognitive or physical, like or additional energy, additional cognitive power, access to certain memory sets, albeit narrow memory sets, etcetera.

And what you find is that the results point directly to the fact that whatever you believe about stress, provided the information you have, is true, is what happens. So if I tell you that stress improves your memory, focus attention, one observes that. If I tell you that stress depletes your immune system, et cetera, one observes that. So this is something that we don't quite yet understand as neuroscientists. And the psychology of it, it makes more sense, frankly, than the mechanisms. But it's becoming very clear that what we believe about a given phenomenon strongly impacts how it shapes our response to that. So I find that very interesting. Now, of course, you can't delete information about stress being bad for you. So what does that mean if you want stress to be enhancing, as it's called? There's literally now called the stresses enhancing mindset, that the thing you can do is to learn more about how stress can be enhancing. We're not talking about lying. We're not talking about placebo effect. We're talking about real knowledge based in fact that one can absorb, and I find it amazing and wonderful that the mere learning of something can actually change how we respond to something at a core physiological level.

The second, I think, very important set of findings on stress relate to a structure that I've talked about recently on the podcast, and I talked about with the one and only David Goggins. Most people presumably have heard, like, he's on his way. He's running here right now from Central America. Yeah, that guy. I'll tell you, that guy is every bit as intense as he comes across. I met him for the first time in 2016 at a gathering. It was in Silicon Valley. We're just doing a little bit of work for this company. At the end of the day, he leaves for a minute, and he changes into his shorts and his shirt. He's like, I'm going running. I gotta go to the airport. I'm thinking, I'm gonna go running. Then I'm gonna go to the airport. He was running to the airport. Seriously? It went like 14 miles from the airport, which I realized 14 miles from a marathon are no big deal, but he's got his bags, and I'm thinking to myself, this guy is nuts, and I love him. I mean, he's really that guy. It's actually very refreshing. I think one reason we love the Rick Rubins and the David Goggins is they truly are different.

But from one basic standpoint, they just don't give a shit. They just do what they're gonna do, and they trust that they're doing right for them and for the people around them. And it's awesome. It's really awesome. I think that it, again, brings about that word that doesn't come about very often for me, but you just kind of stuns you into, like, behold David Goggins. Rick Rubin, the cuttlefish. Whatever. But I talked about this with David. There's a structure in our brain, and these are recent discoveries. Not by my lab. I wish I had discovered these, but actually, a colleague of mine at Stanford, Joe Parvizi, who's in the department of neurosurgery, has made these beautiful discoveries about the anterior midsingulate cortex. The anterior midsingulate cortex. There's a structure in the brain that has a lot of subdivisions. But when Joe put a little stimulating electrode into this area, because he had patients that needed neurosurgery, and they probe around asking questions, what do you feel? How do you feel? What are you going to do? And sometimes they hit an area. I've seen these experiments. They're unbelievable. Stimulated an area. And the person says, you know, I feel like I'm about to go into a rage.

They're like, okay, let's back off. Let's move over here. Anterior mid cingulate cortex, they stimulate, and the patient, the person says, I feel like I'm heading into a storm. You go, oh, that doesn't sound good. And they say, no, but I'm ready. I'm leaning in a different patient, you stimulate their anterior mid cingulate cortex. And the person says, I feel like I'm going to get up out of my chair and do something really, really difficult. So this is interesting. Across multiple people, you're seeing the same general kind of forward center of mass kind of response, leaning into challenge, and challenge specifically. And then there's now scores of studies in just the last three to five years showing that, for instance, people who successfully overcome a challenge of any kind, fitness challenge, cognitive challenge. Anterior mid cingulate cortex expands, or at least increases its baseline levels of activity. You see people that fail to meet that challenge, less anterior mid cingulate cortex activity. So there's a bi directionality of the response and on and on. And it seems that doing things that are difficult, that we don't enjoy, or that we have to push ourselves to do, grow and enhance the activity within this anterior mid cingulate cortex.

And the beauty of it is that it generalizes that the anterior mid cingulate cortex can be applied, or the growth of it can be directed towards lots of different things, which is, I think, a call for, of course, seeking pleasure, seeking comfort, seeking relaxation, seeking sleep every night, seeking sunlight in the morning, etcetera, but also deliberately seeking out challenges, that is, challenges for us. The importance of doing hard things in a safe manner, psychologically and physically safe manner, of course, is truly beneficial toward our ability to manage ourselves in what would otherwise be called stress. So I think those the work of Ali Crumb and the work on the interim cingulate cortex by Parvizi and a bunch of other labs, I think, are the two areas where I feel like things are happening really quickly. We're making big strides as a field, and we're moving away from kind of conjecture about how to better ourselves in lots of different ways. Can you talk about time perception? Why is it that in some instances, time moves very slowly, while in others, it seems to move very fast? Thank you. Tonight has been so fun. Thank you.

I've had fun, too. This is something I'm trying to do more of, not necessarily live that, too, but someone recently, who I love and admire very much said to me, we're going to have so much fun. And I thought, oh, like, behold, no one's ever said that to me. No one's ever said that to me all my years growing up. I mean, I love, with all due respect to my parents, I can't remember anyone ever turning to me and saying, we're gonna have so much fun. So I'm trying. That, to me, just kind of blew me away. I'm thinking, yeah, like, you're allowed to have fun. So time perception is a topic that I am, you know, as obsessed by as I am many other topics, but one that is really near and dear to my heart, because I've always been struck by this observation that is certainly not uniquely mine, that, you know, if you're sitting waiting for an appointment at the doctor's office, it feels like time goes by really slowly, like, really slowly. Whereas if you have a really full day with lots and lots of activities, it seems like time went by really fast.

Like, oh, my God, I can't believe that so much time has gone by. Sorry. So much has happened. Excuse me. But not a lot of time has gone by, which means that our frame rate on life is highly dynamic. And in fact, it is. And in fact, it's set by, you guessed it, our visual system, at least for sighted folks, for people who are low vision or no vision. And by the way, I always reference that because my laboratory has worked on low vision, no vision issues for a number of years. It's through the auditory system. But for sake of generalizing now and simplicity, we'll talk about the visual system. So it is a fact that when we focus on things up close, think a watchmaker. Think about looking into your phone. Our perception of time is more fine grained. That is, our frame rate is higher. Okay, so more frames per second than when we view things at a distance. You might think, well, how could that possibly be? How can that possibly be? But it makes perfect sense. You know, when we think about the time space coding in the brain, we need to anchor ourselves to something.

The rising and setting of the sun, of course, the, you know, I mean, unless you're a flat earther, you know, we're going around the sun. Yeah, what's that? We got no flat earthers. One flat earther in the audience. Okay, cool. I don't think that's what they were saying, but. But we need to anchor ourselves in time. And our visual system is the way that we anchor ourselves in time. We have facts about past, present, and future. So we have knowledge, but at an unconscious level, we need to anchor our frame rate, set our frame rate. And so this is why if you go down to Bondi and you lie back and you look up at the clouds, and the clouds are kind of moving in an unpredictable way whenever we're looking at a landscape which has some lack of predictable features, like waves or rustling of trees, where you could predict that if the wind's blowing this way, that the tree's going to go this way and then back again. But you're not really in a mode of trying to anticipate just how far. In the same way that, for instance, if you call an Uber, you're waiting on a text message.

You know, if you're ever waiting on a text message, you notice, you'll find, slice, okay, dot, dot, dot. When's that thing coming? When's that thing? You're fine. Slicing time. As your level of autonomic arousal goes up, your frame rate goes up as your level of autonomic arousal goes down, so you're sleepy. Or if you're viewing things that have kind of an unpredictable aspect to them, then your frame rate expands. The passage of time changes, or your perception of the passage of time changes. This is why. One of the reasons why I love Aquaria, you know, and one of my favorite things to do, since I don't have a fish tank at home right now, but that's going to change soon, is I'll go on YouTube, and there's this beautiful live video of this aquarium in Japan, and I'll just zone out. It's like the most relaxing thing ever. And every once in a while, a whale, they have a whale shark in an aquarium. Every once in a while, a whale shark will go through and go like, whoa. And then it disappears. And then the little fish and the kelp and things like. And it's immensely relaxing.

What it does is it slows your frame rate down. And then I find that resets me after just five or six minutes to go back to doing this, you know, high frame rate type stuff, which is what we're doing when we're texting, when we're typing, when we're social media, by the way, is tuned to a frame rate that's really interesting, that keeps us engaged just up into the point where then we want to swipe to the next thing the algorithms are designed. And by the way, I have a somewhat benevolent, semi benevolent view of social media. I think it would be used for good. I think it would be used for not good. I think limiting one's time on there is good, but there's some good content on there for sure. A lot of my life is spent on there. Indeed. So frame rate is set by where you're looking. The further out you're looking, the larger, the longer sort of time bins you're capturing. Bigger time bins, okay. Less resolution, closer in, and the more you're trying to predict the next outcome. Sort of fine grain analysis, predicting what we call dpos, duration, path, and outcome.

What's going to happen for how long, and what's going to happen is something that you're thinking about and wondering about. Then frame rate goes up, and there's actually a wonderful movie, a Hitchcock movie. The name escapes me at the moment in which Hitchcock understood this. And it's a movie that's only about 90 minutes long, but in the background, the sun rises and sets. And the way that people move through the scenes of this movie gives you the feeling by the end of this 90 minutes movie that a full 24 hours passed. It's really interesting. You feel it in your body as if it was a much longer movie, even though if you look at your watch, that happens. And now the cannabis smokers again are thinking like, yeah, like, where you sit there and you're like, whoa, that was a really long time. You look and it's like three minutes went by and you're like, whoa. Like, wow. Psychedelics will do this as well? They certainly do. They distort our time perception mainly through the deployment of large amounts of the neuromodulator serotonin, which is intimately involved in our kind of clock perception mechanisms. There are a bunch of other things that can set sort of intrinsic rhythmicity of our auditory system that also adjust our frame rate.

I think one of the reasons why 40 hz tones can be valuable for doing cognitive work is that they tend to entrain certain circuits within the brain for doing the kinds of work that most people call work, where you have to type things out, think logically, kind of if then kind of analysis very different than, say, writing new sheet music or coming up with poetry where, you know, here again, we can think back to the, you know, the Rick Rubin thing or being stationary, right? Like the wall we're sitting with a movement and the brain going forward. There's something about adjusting frame rate for capturing new ideas versus implementing ideas. Implementation of ideas tends to be carried out on higher frame rate type time perception. And now you can understand why visual perception set about the distance of a laptop or phone would be good for that. Or a conversation. Remember that whole thing of looking at somebody's face and having a conversation, as opposed to looking off into the distance, walking and allowing one's gaze to go panoramic. So hopefully, now you're starting to sense some themes. So that's all I'll say about time perception now.

But of course, humans have throughout history, and still now, frankly, also embarked on a lot of pharmacology, if we're honest, in order to try and adjust frame rate for sake of productivity. But caffeine will adjust frame rate in the predictable direction, but also things like alcohol and various drugs like cannabis in order to adjust frame rate. I'm certainly not suggesting you do those things. I'm not a cop. You do what you want. Just know what you're doing. Can you please talk about the jet lag protocol you followed when arriving in Sydney? Oh, yeah. Well, this one was a little bit easier for me because obviously it's not that far off. It's just you're a full day ahead from where I live back home in California. But nonetheless, I suffer tremendously from jet lag. And once, actually, in 2017, I went to Abu Dhabi. Twelve hour flip from where I was living at that time in the Bay Area, and I was a wreck. I could barely make it to the meeting. I was crying. It really messes me up. I slept great the first night and then just didn't sleep for two days. I was a mess.

So jet lag is something that I really had to work hard on. And there are a couple things worth noting, and we've done a whole episode about this, but I'll kind of hit a few key bullet points. And maybe it's relevant to you even if you're not traveling at any point soon, because many people are jet lagged without traveling because of the way that they stay up late. In fact, most everybody in the world now qualifies as a shift worker. Did you know that? And here, no disrespect, only reverence and gratitude to the actual shift workers that stay up all night doing emergency work and hospital work and caring for children and things like that throughout the night. So I'm not trying to take anything away from them. But we are all shifted enough, by virtue of artificial lighting and electronic devices, that we are effectively shifted and shift working because we're staying up, engaging our cognitive systems in ways that, frankly, we didn't evolve to. Which I'm not saying is bad, but it's just the reality. Okay, what to do for jetlag the key thing is this. And actually, this is very valuable in general for sake of sleep.

So, this is something I haven't talked enough about on the podcast. Ask yourself what time you normally wake up without an alarm. I realize there's some variants from day to day, but, you know, for me it would be about, let's say, 06:00 a.m. So let's say for you at seven, you know, just pick your typical wake up time if you subtract from that number. So, for me, 04:00 a.m. That almost with certainty is what's called your temperature minimum. Your temperature minimum. We could measure it. You could put a thermometer in your mouth, or if you come to the laboratory, unfortunately, they have to do it rectally. 04:00 a.m. Would be my temperature minimum. Maybe for you, if you wake up at seven, typically or around seven, it's gonna be 05:00 a.m., okay, so we're not actually measuring your temperature in this kind of, in this thought experiment. What we're doing is we're trying to find a time. So here's what's interesting. If you expose your eyes, not your skin, but your eyes, to bright light in the 2 hours or so, maybe 3 hours prior to that temperature minimum time. So if you wake up at 07:00 a.m. 05:00 a.m. Is your temperature minimum.

So in the 2 hours, maybe 3 hours prior to that, you're going to shift your wake up time and your to bed time, what's called a phase delay, a shift in your circadian rhythm by about an hour. Interesting, given that if you view bright light in the two to 3 hours after your temperature minimum, you advance your clock, meaning you pull back your clock to want to wake up a bit earlier and go to sleep a little bit earlier, by about an hour. For every time you do that, you think, well, okay, I wake up in the morning at seven. Let's say I'm using you as an example, or me at six, and I usually try and get some sunlight in my eyes, especially on overcast days, etcetera, etcetera. You've heard me blab about this many times before on the podcast and elsewhere. So how come I'm not going to bed earlier and earlier every night and waking up earlier and earlier every morning? And indeed you would. You would keep phase advancing your clock if you did that. Except that in the afternoon, if you got sunlight in your eyes, as presumably you did today, it was a beautiful sunny day.

On your way here, you phase delayed your clock a little bit, and as a consequence, you wake up and go to sleep at more or less the same time every day. It's an amazing mechanism. And guess what? Viewing sunlight in the middle of the day does not do the same thing. It doesn't shift your circadian clock. They don't tell you that in school, but they should. They're telling you, like, all the other stuff. The reason it doesn't do it is that middle of the day period is what's called the circadian dead zone. Sounds very dramatic, very ominous. Getting sunlight in your eyes during the middle of the day is great for mood. It's evident that it's also important if it gets on your skin and healthy, not burning amounts, levels that would induce burn, that it can enhance testosterone and estrogen levels, et cetera, in healthy ways, healthy ratios. Nonetheless, that morning sunlight viewing after your temperature minimum advances your clock makes you want to get up earlier, go to bed earlier. Viewed before delays, your clock makes you want to get up later, go to bed later. So this is very useful if you ever want to shift your clock at home before you travel to get onto a new schedule for work or school or if you're traveling, what it means is that when you arrive in a new location, like I did in Melbourne the other day, believe me, I practiced that for, like, at least an hour and with two Aussies, and they kept telling me I was doing it wrong until finally they're like, no, I'm just joking with you.

You got it right, like the fourth time. You guys have a wicked sense of humor down here. The I'm tougher than I look. The key thing is that if you land, you have to ask, let's say at 08:00 a.m. Local or noon local time. The key is to ask yourself, hmm, what does my body think? What is my temperature minimum from back home? So, for instance, if you land at 05:00 p.m. But it corresponds to time before your temperature minimum, and you go outside and like, whoa, beautiful setting sun. I'm supposed to get sunlight in my eyes? Well, guess what? You might delay your clock. If you want to go to bed earlier, that's probably not a good idea. Whereas if you want to, if you want to advance your clock, you would view sunlight at a time that is corresponding to the 2 hours after temperature minimum. I realize it's a little bit tricky, but that's all you have to ask yourself for the first three time days, first three days that you travel to some location because then you can shift very fast. So what that requires is sometimes saying, oh, I don't want to shift myself.

So I'm actually going to wear sunglasses and a brimmed hat to avoid shifting because I'd like to be on the local schedule or in some cases think, oh, I really want to wake up here. And I'm in the perfect opportunity to wake up because it's the middle of the afternoon in Sydney, and back home, I would have just hit my temperature minimum. And so I'm gonna get sunlight in my eyes. Well, that's going to wake me up and it's going to actually make me want to go to bed a little bit earlier so I can go to bed at local time. So I'm not going to be up until, you know, 03:00 a.m. So you might have to work this out a little bit on paper, but this is the way that military and this is the way that shift workers who are educated in the, in the mechanisms of this stuff, that's the way they do it. It also helps to eat on the local schedule because food is another what we call Zeitgeber, another one of the timekeepers for the circadian clock. So if you force yourself to eat on the local schedule, that can help you shift.

Activity can help you shift, and social rhythms can help you shift as well. But that temperature minimum and the role of light before or after the temperature minimum, either delaying or advancing your clock, that's the heavy hammer in this whole process. So I did that. And these days I do a lot of red light time in the evening when I want to go to sleep. And I don't mean red light panels, like the expensive stuff that has a whole other set of uses. What I'm talking about is just getting a red light, like a party light. We turn off the lights and put in a red light. And that is known to reduce cortisol levels as opposed to other kinds of lighting. So it only takes about half hour before you go to sleep or so you want to just mellow out, you just switch over to red light. It's actually very pleasant. Right. As long as you can go about the activities you want to do safely. Just put a red light up. And by the way, Rick's house is like all red lights at night. No artificial lighting past sundown, guys, like a plant.

Can you elaborate on the science between psychedelic psilocybin and neuroplasticity? Yes. You know, this is a topic that just a few years ago I was like, too frightened to talk about. I was afraid to lose my job, frankly. You know, these are still scheduled drugs in the United States, although they are being explored for. For therapeutic reasons, mainly for the treatment of severe depression, but among other things, smoking cessation, eating disorders. By the way, anorexia nervosa still is the highest morbidity of any psychiatric challenge. It's just really tragic. So there's a real need for treatments that work. And psychedelics like psilocybin, LSD, to some extent, MDMA, which technically is not a psychedelic, it's an empathogen. We could talk about that. Also called ecstasy. So these sorts of compounds have been explored quite extensively in the last few years, and I've completely revamped my stance on them for a couple of reasons. I'll just come clean. You know, as a kid too young, I explored these things. I do not recommend that. I had some pretty bad experiences on LSD as a young teenager, and I don't recommend it. I think the brain is highly plastic that time.

In fact, being an adolescent, a kid, or a teen, is a psychedelic experience. You do not need psychedelics, and I don't recommend them unless some very qualified clinician can convince you otherwise. And there I would also seek a second opinion, but they clearly have their role, and I think a couple of things have changed my stance. First of all, there are a lot of federally funded studies taking place at Stanford and elsewhere on these compounds. Second, for whatever reason, and I don't quite understand the sociology of it, but for whatever reason, psychedelics are no longer associated with the kind of counterculture the way they used to be, and are in fact, heavily associated with some of the veterans groups that are using these for PTSD, with groups in the states, groups like veterans solutions, which are doing amazing work with different psychedelics, including ibogaine, eboga, which is a 22 hours long psychedelic journey. I've never done it, truly, where you close your eyes and you get essentially real life like recollection of your experiences, but you have agency inside these experiences. There's some cardiac issues with ibogaine that require constant monitoring of the heart, but they've got some really impressive outcomes.

This is all work by my colleague Nolan Williams, Stanford. So things like psilocybin, we view a little bit differently nowadays. What is psilocybin? Psilocybin, if you look at it chemically, looks a lot like serotonin. A lot like serotonin, and it tickles. That is, it binds nearly selectively to a specific serotonin receptor. And it seems to create more what we call resting state lateral connectivity, which means more brain areas connected to other brain areas, or at least talking to those brain areas after the psilocybin journey, as it's called, as opposed to before now these journeys, and I have done them as an adult. I did this as part of a clinical trial. I participated in a psilocybin trial, and I participated in MDMA trial. They can be terrifying while they're happening, but often there's great insight from those experiences, provided the right support is provided. And they always say set and setting. So I'm not providing all these caveats about safety for no reason or to protect me. I'm saying to protect you. I mean, it can be, and it was, for me, absolutely terrifying. And then you do it again as part of these trials.

The second time, I'm like, okay, this time it's gonna be good. Boom. Terrifying. It was horrible, but I learned a lot, and there does seem to be an antidepressant effect. I wasn't clinically diagnosed with depression, but prior to that. But we're after, thank goodness. But I think what we're seeing with these compounds, and from my own experience, if I may, is that they allow us to see relationships between events of past and present, and hopefully anticipate certain actions and changes into the future while experiencing the fullness of the emotionality of those experiences in real time. So, as somebody who's done an immense amount of therapy, I can tell you that I find great value in talk therapy. I do, especially of the. I think what's called insight oriented psychoanalysis or psychotherapy doesn't have to be classic psychoanalysis. Not just support. You need that. Not just rapport, you need that. But insight as well, is the goal, those three things. But one of the issues is, unless you get on the phone with your therapist or you talk to them in person, in a moment where something is really acute, like it's really getting you right at that moment, sad or happy or whatever it may be, it's hard to experience the fullness of that issue in that moment while also parsing it cognitively.

And it does seem that the psychedelics and to some extent, MDMA allow people to get into the full amplitude, maybe even enhanced amplitude, emotionality of an experience, and at the same time, allow people to reflect and with the help of a so called guide or the therapist, take notes in a way that lead to specific, actionable outcomes. And I think that's the real value. You can get real time experience with insight, and of course, you need support as well. And of course, set and setting and safety are absolutely key. So psilocybin seems to do that in one manner. MDMA does it in a different way. MDMA, by the way, we know, dramatically increases serotonin and dopamine, but it seems to be the serotonergic effect that is responsible for most of its therapeutic effect. By the way, MDMA is methylene dioxymethamphetamine, which isn't necessarily saying that it's bad. What's actually interesting is that MDMA ecstasy, provided that it's pure and in the appropriate dosage range, does not seem to be neurotoxic as it once was thought to be. The paper claiming that was retracted, they accidentally were giving the subjects in that study methamphetamine, not MDMA.

And. Right, yes, right. And they retracted the paper, but nobody talks about that paper. But do you know, it's kind of interesting. Do you know where most of the data on the lack of toxicity of MDMA comes from? There's a beautiful set of studies that were carried out on subjects who were exclusively from the church of latter day Saints, sometimes referred to as Mormons. Right. Mormons are an excellent test population for a study like that because they don't do other drugs. But MDMA is not on the no fly list. So apparently, according to these papers, and by the way, I have a lot of friends who are LDs, and they're wonderful people, according to these papers, which I believe because they're published and peer reviewed and they still are in the literature, you can find subjects in that community. Not all LDS folks are taking, I don't think. But presumably. No, but people who have taken anywhere from one to two to 50 to over 100 doses of MDMA in a short period of time. And aside from a mild deficit in attention in the people who have taken the large doses or frequent doses, that is, there do not seem to be many cognitive deficits that are detectable and certainly no apparent neurotoxicity, which is not to say go do MDMA as much as you like.

I think there is the potential for neurotoxicity if it's taken too often and things of that sort. So a lot to still figure out. But MDMA seems to have a slightly different trajectory than psilocybin. It tends to be less scary, although it is very sympathetic arousing, that is, so people can get afraid, or if they have elevated heart rate, etcetera. But the empathogenic component is really interesting because ultimately, with PTSD, it's really about developing empathy for one's self. It's really about developing empathy for oneself and resolving one of the core issues of trauma, which is often not discussed, which is that at an unconscious level, at an unconscious level, trauma seems to be a confusion to the nervous system about who's responsible, so that even if somebody knows and understands, hey, that was them, they're the perpetrator, I'm the victim, somehow the nervous system gets confused about responsibility in a way that leads to triggering of some of the negative feelings around that event, or events, as the case may be. And MDMA seems to be able to intervene in that confusion and short circuit that confusion through this self empathy. Self empathy is something that I think deserves more exploration in the years to come.

So lots happening there in the United States. MDMA is now being registered with the FDA for additional, perhaps for legalization. Right now, it is still illegal. So if you take any of what I said tonight and go buy MDMA, I'm not at fault. Getting in the sauna about 2 hours before going to sleep really improves my quality of sleep. What's going on here? Ah, love this. This one can be pretty simple. The relationship between temperature and sleep is a well established one. To fall asleep, you need to cool down by one to three degrees. You've probably heard me say that before. To wake up, you need to heat up by about one to three degrees. And when you get into a sauna or you take a hot bath, or even to a lesser degree, you wash your face with warm water in the evening, hands with warm water. Because of the way that the body thermoregulates, you actually end up cooling yourself off. You think, no, I got in the sauna. Actually, I've been going to the sauna at this place here, recovery, they have a wonderful sauna, cold plunge, and then they have this bed where you float on the thing.

Have you tried this thing? This thing is so cool. It's like a waterbed, but it, like, floats you. That's amazing. Amazing. By the way, they don't pay me to say that. I'm just grateful that they let me, like, sit in this bed. I've been sleeping in there as much as possible, but they shut down at night eventually, and I gotta go home. So the sauna's a great tool before sleep or warm shower or hot bath or warm bath for the following reason. The brain area that controls thermoregulation is the medial preoptic area, which operates like a thermostat. So if you warm the external portion of the body. The brain has to then what? Cool down your core body temperature. It doesn't happen right away, but it happens as you get out of the sauna, and maybe you take a warmest shower or cool shower. So what ends up happening is that you warmed up, which allows you to cool down internally, and then you're able to fall asleep and stay more deeply asleep. That's probably what's improving your sleep. In fact, a kind of mantra that I learned from the great Matt Walker, who wrote the great book why we sleep.

And by the way, we have a sleep series with the mighty Matt Walker coming out later this year. We record six episodes. All, every aspect of sleep you can imagine. He says, and I hope I'm getting this right, he says, you need to warm up to cool down to go to sleep, or to fall. Warm up to cool down to fall asleep. Stay cool to stay asleep. Warm up to wake up. There you go. That's a straight bite out of Matt Walker's mouth, so he deserves that citation, not me. So that's what's happening when you get in the sauna. Now, when you get into the cold plunge, you're cold. But guess what? Same thing. The surface of your body is cooler. Those thermoreceptors transmit information to the medial preoptic area of your body, and your core body temperature eventually goes up, provided you don't stay in there. Get hypothermic, of course. Okay. People are always asking me, I have a good friend who just so happens to be straight edge. He's like, never. Never even has sip of caffeine. I don't know. It's a good thing because he's extreme. And he got a cold plunge, and he went in for a minute, and then the next day, he's like, I did three minutes, and then pretty soon he's like, hey, I got a sick.

I was like, what do you do? He's like, I got naked in the cold plunge for 45 minutes. I was like, well, listen. I'm like, first of all, thank goodness you don't do drugs. Second of all, like, easy does it. Easy does it. Cold is a very powerful stimulus, as is heat. So, you know, minimal effective dose. You know, have some fun with it, but don't go wild. I still don't know why you got in there naked, but who knows? If we expose ourselves to the same stress over and over again, do we release the same amount of adrenaline and its positive negative impact and just becomes less receptive? Do we release less adrenaline? And hence, it's less harmful? It's a great question. Depends on the context. Typically, you'd release less and less adrenaline. And actually, this relates to a really important fact about the ever famous structure, the amygdala, which means almond. I don't know why I told you that. It happens to be shaped like an almond. The amygdala people associate with threat detection and danger, but it's actually a novelty detector, essentially, and it's involved with a bunch of other brain circuits that anytime we experience something novel, you know, we have an elevated level of autonomic arousal.

Like, earlier tonight, before the show, there was a kind of a repeating dong, ding, ding. And the first time it happened, I'm like, is there a fire alarm? Like, what's going on? By the time it happened five times, I was kind of like, eh? So that's sort of we. I'd be willing to bet both amygdalas, if we recorded from my amygdalas, it's got one on each side of the brain. You would find that. That the first time there's a big increase in activity. Lesser, 2nd, 3rd, 4th, fifth, and you attenuate, you habituate. So if the stressor is one in which you don't care, it doesn't have much relevance to you. Like that alarm, probably less and less adrenaline. I'd be willing to bet, however, if with each subsequent exposure, like somebody you really can't stand or something like that, it's decreasing your life satisfaction and increasing your level of cognitive or psychological stress, then it would go in the opposite direction. I think that's. That's fair to say. Hey. Hey, Andrew. Holly. I like that. Hey, that's cool. Yeah, the other day, it was really interesting. Every once in a while, someone will walk up and be like, hey, listen to the podcast.

Which is always nice. It's always nice to meet people. And this kid walks up to me, this was in Melbourne, in the gym. Like, this has never happened to me before. It was really cool. He just walks up. He goes, hey, Andrew. I'm like, cool. He just said, that's it. And he just walked away. I was like, right, like, cool. And I was like, that kid is so mellow. It was really cool. Like, I was like, we would have been friends. Actually, I was friends with all the wild ones, but it was a really interesting phenotype. Again, human phenotypes fascinate me. So if we run into each other on the street and I ask your name, and we talk, I'm genuinely interested. I'm not studying you. I'm not taking notes or data, but people are so different. But hey, Andrew. Okay, so maybe it's him. Hey, Andrew. Hey, Adi. I found that I'm able to focus far better when I bounce my legs up and down while sitting on the balls of my feet. What's going on? You got a lot of energy. That's what's going on. No, I think, you know, there isn't a ton of science on this, but it's very clear, as I mentioned earlier, that people have different spontaneous movement rates.

And some people, you know, some people are a little bit more jittery. If you look, if you go into a classroom, young children see them sitting around, boys and girls, let's say somewhere between four and six. Oftentimes, you'll notice that some of the kids can sit extremely still, and then some of the kids are like, really? Like. And there is a chromosomal difference there. It's known that boys have a slower development of the so called top down inhibition from the forebrain, the prefrontal cortex, which, frankly, we hear about over and over again, many podcasts. A lot of description of prefrontal cortex, its main job, the best description I've ever heard of it, anyway, is from a friend who's a neurosurgeon at Neuralink who came up through my lab, Matt McDougall. He's been on the podcast. He said the job of the prefrontal cortex is to send connections to the rest of the brain and say sh basically to the appropriate circuit. So it's. That's why people with damage to the prefrontal cortex for any reason or neurotransmitter degeneration of the prefrontal cortex find themselves doing things, or we find them doing things that are a little bit context inappropriate and in some cases, dramatically inappropriate, but in most cases, just kind of context inappropriate.

They don't suppress behavior very well. So, you know, it may be that a certain level of autonomic arousal brings us into that optimal. You know, some people call it a flow state. Flow state is a little bit of a nebulous thing. I mean, I have great respect for Steven Kotler and those that have talked about and written about flow, but what I really can just say about flow as it relates to neuroscience is that, like, backwards, it spells wolf. Like, we don't really know that much more about, like, the neural basis of a flow state, but for each of us, we have these kind of tunnels that we like to be in where we find that our level of focus and action is just right and so I don't think I'm going too far out on a limb here. Adi, by saying that if you find that you focus best when you can dispel a little bit of that energy by moving your body, that you're able to do your best work. That makes sense to me. I don't do them so much anymore, but for years, I would do, you know, surgeries, lots and lots of surgeries down the microscope, dissecting retinas.

Dissecting retinas. Like, if you got an eyeball, I can dissect it. I'm good at it. I can do them in my sleep. And I would find that if I had a little bit too much energy, that the forceps would jiggle a little bit. And it wasn't a caffeine thing. And a friend of mine who's a world class neurosurgeon, Eddie Chang, who's chair of neurosurgery at UCSF, he's been on the podcast, he said, ah, there's a solution to that that we learn in neurosurgery. They're like the astronauts of medicine. He said, you know, you tap your foot. I thought, that's kind of cool. Why would that work? He said, well, basically, you've got some sort of anticipatory activity in an area of the brain called the basal ganglia, which is involved in these go no go type actions. Like all of our actions are yes go and no go. Don't do something else. No flexor, extensor. There's all kind of stuff very complicated, but it's seamless for most people. And when you have a bit too much anticipatory activity, you're getting ready to go like a sprinter out the blocks, and you're doing something that's very important, like a brain surgery in his case, or microsurgery in my case, for research purposes, that if your activation state is too high, that you can dispel some of that energy by just simply tapping your foot or doing some sort of rhythmic activity with another part of your body appropriate to that context, of course.

Okay, last question. I don't know. Hey, Andrew. Yeah. Oh, oh, they skipped that one. I guess that's the new thing I'll never forget when I got my lab for the first time. You know, I came up in an era when it was still pretty formal neuroscience. You know, like, you'd say, hey, professor so and so. And then they say, you can call me Barbara, and I'd be like, hey, Barbara. But before that, no one you know, hey, or that. And I'll never forget that in my lab. One of my first graduate student, who now a professor, very, very talented scientist at the University of Utah, and I got a text from her and just said, she called me Andy. She said, hey, Andy, when are you going to buy us an espresso maker? It was like the second day and I was like, whoa, times have changed. So I think it's good. I think the lack of formality is actually good. At first I was like, wait a second. I waited my whole life to become a professor and now it's, hey, Andy. But I think, you know, with the years, I've realized that it's actually kind of nice.

I'm 17 years old. Congratulations, man. I wish I, you didn't want to know me when I, I was a nice kid, but I was just a lot of confusion. I'm 17 years old. So you're in a psychedelic experience of youth. What is your biggest advice on finding your passion? Oh, well, goodness gracious. I think, you know, I, if I'm honest, I think we talked about it a little bit earlier. I think your passion is rooted in a feeling state that you've already accessed, hopefully many times, but at least one time earlier in your life when, for whatever reason or circumstances, you weren't thinking about what your parents wanted you to do, what was cool or not cool in school, you were in a pure feeling state of yummy. That's really cool. Behold. And so I can't answer the question for you, but I'll tell you. Yes, continue to forage. I do believe that learning is among the most wonderful things that we can do for ourselves, but that if you spend some time in your memory banks, that you'll be able to remember a feeling. And maybe the feeling was about a board game you played or something you observed, or maybe it just came about through some other activity and the feeling is unrelated to the activity.

That's where it gets a little tricky. And we're answering this question for a 17 year old, but it's true for all of us. This is where it gets a little tricky, is that sometimes we think it's the activity, but it's not the activity. I mean, Lord knows I stay out of the Aquarius doors these days, you know, because if I go near one, it's all over. No, it's that. It's the, it's the delight in something that is very personal. In fact, I think is very unique to you to the extent that, and I do believe this, that it's not capable of being created by anybody else. And that feedback from other people about what we should do or what we're good at, while it can be useful, it's merely a calibration point for saying, like someone says, maybe you should do this. And you go, or like, meh. Or like, yuck. Those are all just calibration points on this like compass to take you back to that feeling state. So I apologize for not having a more concrete mechanistic. Works the first time, works every time. Kind of instant tool, like a physiological sigh, rather.

This is going to have to be some self exploration. But the good news is, you're 17. Your brain's still plastic. The good news is, all of us are capable of neuroplasticity throughout the lifespan. And the good news is, all of us are capable of introspection throughout the lifespan. So even if you can't remember, you can sense. And if you can sense, what you're doing is you're feeling. What is this? I don't want to turn this into a neuroscience lesson, but I'd be remiss if I didn't say that you're perceiving and feeling on the basis of converting physical information in your environment. Sound waves, photons, mechanical pressure, chemicals going in through your nose and mouth. You're converting that into electrical and chemical signals. That's what being and perceiving really is. It can't be anything else. So there's something about the way that you're wired, Oscar, that is different and leads you to say, yum. Yeah, yeah, yeah, yeah. That. That. And for me, I've always associated with a certain physical sensation in this arm. Don't ask me why. I don't even know. And if you can sense into what it is that gets you going in that direction, if any and all of us do that, then I really believe you can sense into your unique gifts.

Or maybe you just need to sit back and think in deliberate, complete sentences for an hour, like Rick or one of those other geniuses. I don't have a better answer. That's the best I can do. Thanks so much. Thank you so much. Thank you. Thanks so much. Thank you so much. So, just as a final note this evening, I just want to thank everyone for coming out. As Rob mentioned to, you know, come out. As far as I know, there's no alcohol here. People are here. Amazing. An event with no alcohol on a Saturday night in this beautiful Sydney summer where we talk science. Thanks for letting me tell some stories, learn some stories. My real wish, my deep wish, is that everyone do some level of introspection, if not tonight, going forward. And I so appreciate that people are interested in the concepts around science and health. And the really big, big wish for me, maybe I'll even just call it an ask, is that I truly don't develop the protocols. I mine them. Occasionally I develop them, but I mine them from the rich sources of information in papers and elsewhere and put them into a format that I'm deeply appreciative.

People enjoy digesting and hopefully apply, but hopefully share. And I certainly don't need attribution. None of them are named after me intentionally because that's not going to give them any information about what they do or how they work. And last but certainly not least, thank you for your interest in science.

Thank you to the Sydney Opera House Trust for their hospitality and for making this event possible. And last but certainly not least, thank you for your interest in science.