
LIVE EVENT Q&A: Dr. Andrew Huberman at the ICC Sydney Theatre
Andrew Huberman (host), Narrator, Narrator, Narrator
In this episode of Huberman Lab, featuring Andrew Huberman and Narrator, LIVE EVENT Q&A: Dr. Andrew Huberman at the ICC Sydney Theatre explores andrew Huberman Unpacks Sleep, Psychedelics, Focus, and the Gut-Brain Axis In this live Sydney Q&A, Dr. Andrew Huberman answers wide-ranging audience questions on sleep, stress regulation, learning, psychedelics, ADHD, and the gut–brain axis. He emphasizes zero-cost behavioral tools—like non-sleep deep rest (NSDR), physiological sighs, and visual focus training—as the foundation for mental and physical health, before supplements or medications.
Andrew Huberman Unpacks Sleep, Psychedelics, Focus, and the Gut-Brain Axis
In this live Sydney Q&A, Dr. Andrew Huberman answers wide-ranging audience questions on sleep, stress regulation, learning, psychedelics, ADHD, and the gut–brain axis. He emphasizes zero-cost behavioral tools—like non-sleep deep rest (NSDR), physiological sighs, and visual focus training—as the foundation for mental and physical health, before supplements or medications.
He explains how belief and placebo effects can measurably change brain activity, why naps and NSDR affect night-time sleep differently, and how agitation and stress actually trigger neuroplasticity during learning, while sleep consolidates it.
Huberman also gives a nuanced overview of clinical research on psychedelics and MDMA for depression and trauma, highlighting both their promise and risks, especially for young brains and vulnerable psychiatric populations. He closes by underscoring the importance of microbiome diversity, consistent sleep timing, and socially sharing effective science-based tools without hero-worship or branding.
Key Takeaways
Use Naps Strategically and Consider NSDR as a Safer Default
Keep naps under 90 minutes to avoid disrupting night-time sleep, and avoid napping altogether if even short naps impair your ability to fall or stay asleep. ...
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Belief and Expectation Directly Alter Brain Activity and Performance
Placebo and more specific ‘belief effects’ are physiologically real—what we believe about a drug or protocol can change neural activity patterns and outcomes. ...
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Stress and Frustration Are the Trigger for Learning; Rest Does the Wiring
During effortful learning (e. ...
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Enter ‘Rest and Digest’ with Simple, Trainable Physiological Tools
To quickly shift out of a chronic fight-or-flight state, Huberman recommends performing 2–3 physiological sighs (double inhale through the nose, long exhale through the mouth), ideally combined with panoramic vision (relaxing the gaze and widening the visual field). ...
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Psychedelics and MDMA Show Promise but Demand Caution and Context
Macrodose, clinically supervised psilocybin sessions appear more effective than traditional antidepressants for some patients with major depression, likely by transiently broadening connectivity between brain regions and changing how problems are perceived. ...
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Support the Gut–Brain Axis Through Diet and Microbiome Diversity
Microbiota inhabit the mouth, skin, nasal passages, eyes, gut, and genitourinary tract, and when well-supported, gut microbes generate fatty acids and other molecules that serve as precursors or catalysts for neurotransmitter production. ...
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Focus Can Be Trained Behaviorally, Even in ADHD
While stimulant medications like Adderall or Vyvanse can meaningfully help some with clinically diagnosed ADHD (by increasing prefrontal activity and lowering impulsivity), behavioral tools are also powerful. ...
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Notable Quotes
“Naps are wonderful if they're shorter than 90 minutes, don't interfere with nighttime sleep, but I'm a big fan of non-sleep deep rest—body still, mind awake.”
— Andrew Huberman
“Our beliefs have a powerful effect on what happens to us physiologically. Placebo effect is changing neural activity—it's not all just what you think is happening.”
— Andrew Huberman
“Agitation and stress and the neurochemicals that underlie them—that is the stimulus for learning. The actual rewiring occurs away from the stimulus, during sleep and deep rest.”
— Andrew Huberman
“Being a child, an adolescent, or a teenager is a psychedelic experience. You do not want to throw massive amounts of neuromodulators in there haphazardly.”
— Andrew Huberman
“The goal is not plasticity. The goal is plasticity directed toward a particular positive outcome. Any time you have plasticity, you have the potential for maladaptive plasticity as well.”
— Andrew Huberman
Questions Answered in This Episode
You mentioned NSDR may replenish dopamine and help ‘make up’ for lost sleep—what does the current evidence say about how far NSDR can realistically compensate for chronic sleep debt, and where its limits are?
In this live Sydney Q&A, Dr. ...
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In the nicotine belief-effect study, were there individual differences (e.g., personality, prior nicotine use, trait optimism) that predicted who was most susceptible to dose-expectation effects on cognition and brain activity?
He explains how belief and placebo effects can measurably change brain activity, why naps and NSDR affect night-time sleep differently, and how agitation and stress actually trigger neuroplasticity during learning, while sleep consolidates it.
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Given that macrodose psilocybin appears more effective than microdosing in current data, how should clinicians and patients think about risk–benefit tradeoffs for people with subclinical depression or ‘stuck’ patterns but no major disorder?
Huberman also gives a nuanced overview of clinical research on psychedelics and MDMA for depression and trauma, highlighting both their promise and risks, especially for young brains and vulnerable psychiatric populations. ...
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You emphasized that plasticity can be maladaptive—what specific post-psychedelic integration practices (e.g., timing of therapy sessions, sleep protocols, or behavioral changes) do you consider essential to steer plasticity toward positive outcomes?
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For adults with ADHD who are already on stimulant medication, how would you practically layer in the visual fixation and distraction-reduction protocols you described, and what markers would indicate that behavioral training is meaningfully reducing their reliance on medication?
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Transcript Preview
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 ICC Theater in Sydney, 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. I also would like to thank the sponsors for the event. They are Eight Sleep and AG1. Eight Sleep makes smart mattress covers with cooling, heating, and sleep-tracking capacity. Now, I've spoken many times before on this podcast about the fact that sleep is the critical foundation for mental health, physical health, and performance. Now, one of the key things to getting the best possible 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 needs to drop by about one to three degrees, and in order to wake up feeling refreshed and alert, your body temperature actually has to increase by about one to three degrees. Eight Sleep mattress covers make it extremely easy to control the temperature of your sleeping environment and thereby to control your core body temperature so that you fall and stay deeply asleep and wake up feeling your absolute best. I've been sleeping on an Eight Sleep mattress cover for about three years now and it has completely transformed the quality of my sleep for the better. Eight Sleep recently launched their newest generation of pod cover, the Pod 4 Ultra. The Pod 4 cover has improved cooling and heating capacity, higher fidelity sleep-tracking technology, and the Pod 4 cover has snoring detection that will automatically lift your head a few degrees to improve airflow and stop your snoring. If you'd like to try an Eight Sleep mattress cover, you can go to eightsleep.com/huberman to save $350 off their Pod 4 Ultra. Eight Sleep currently ships to the USA, Canada, UK, select countries in the EU, and Australia. Again, that's eightsleep.com/huberman. The other live event sponsor, AG1, is a vitamin mineral probiotic drink that also contains adaptogens and other critical micronutrients. I've been taking AG1 daily since 2012, so I'm delighted that they decided to sponsor the live event. I started taking AG1, and I still take AG1 once or twice a day because it gives me vitamins and minerals that I might not be getting enough of from whole foods that I eat, as well as adaptogens and micronutrients. Those adaptogens and micronutrients are really critical, because even though I strive to eat most of my foods from unprocessed or minimally processed whole foods, it's often hard to do so, especially when I'm traveling and especially when I'm busy. So by drinking a packet of AG1 in the morning, and oftentimes also again in the afternoon or evening, I'm ensuring that I'm getting everything I need. I'm covering all of my foundational nutritional needs. And I, like so many other people that take AG1 regularly, just report feeling better. And that shouldn't be surprising because it supports gut health, and of course gut health supports immune system health and brain health, and it's supporting a ton of different cellular and organ processes that all interact with one another. So while certain supplements are really directed towards one specific outcome, like sleeping better or being more alert, AG1 really is foundational nutritional support. It's really designed to support all of the systems of your brain and body that relate to mental health and physical health. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. They'll give you five free travel packs with your order plus a year supply of vitamin D3 K2. Again, that's drinkag1.com/huberman. And now for the live event at the ICC Theater in Sydney, Australia. "Does having an afternoon sleep affect your quality of sleep at night?" Um, great question. I can keep this one pretty brief. Um, we just recorded a six-episode series that will be aired later this year, uh, with the one and only mighty Matt Walker, who wrote the w- marvelous book, Why We Sleep, and, uh, we went into this topic in depth. The business of, eh, naps is the following. Keep them shorter than 90 minutes so you don't disrupt your nighttime sleep. Don't do them at all if it disrupts your nighttime sleep. So if you're somebody that for whom even 10 minutes of napping interrupts your nighttime sleep, don't do that. If you're somebody who wakes up from naps feeling groggy, that's what's called sleep inertia. This is what gave rise to the ever famous napuccino, of having some coffee and then taking a nap, or an espresso and then taking a nap. Again, I get obsessed with nomenclature. Why didn't they call it a espress- espresso nap? I don't know. Naps are wonderful if they're shorter than 90 minutes, don't interfere with nighttime sleep, but I in particular am a big fan of, as many of you know, this business of non-sleep deep rest, of putting the body into what? Body still, mind awake. And we know based on several studies from the University of Copenhagen that that actually replenishes levels of dopamine in certain key areas of the brain that restore mental and physical vigor and do not disrupt nighttime sleep, but rather enhance one's ability to fall and stay asleep or to fall back asleep. So not only are these states of body still, mind awake very beneficial it seems, or p- I should say perhaps for creativity, 'cause that was all Anick data, but we know from real data, from laboratory data on many subjects, peer reviewed, et cetera, that body still, mind alert is actually an effective means to improve one's sleep and perhaps even make up for sleep that one has lost. So I encourage you, if you're a napper, great, and if you have challenges with sleep in any way that you think might be related to your napping activity, that you consider short 10-minute or maybe 20-minute non-sleep deep rest protocols. By the way, they're completely zero cost, and very soon-We will be releasing to our YouTube clips channel s- a 10-minute, 20-minute, and 30-minute non-sleep deep rest protocol that I've narrated. If you don't like my voice, we can ... There are many out there of more pleasant voices. But, um, what might be of particular interest to you is that the visual is of, um, the beautiful sunrise, uh, over Sydney, so you know, it'll bring you home as well. Um, sunrises here are absolutely spectacular. "Do you believe in the placebo effect?" Absolutely, and there's probably a joke there, but I can't come up with it on the fly. Um, how would I know if it's real, that kinda... ? Um, something like that. Um, so the placebo effect is real. Um, our belief about what we've taken or what is happening to us has a powerful effect on our physiology. It's not purely psychological. The whole business of psychosomatic, even that word is starting to fall away as we start to understand that our beliefs have a powerful effect on what happens to us physiologically, so much so that, for instance, my colleague, Alia Crum, a tenured professor at Stanford's Department of Psychology, who's been a guest on the podcast who studies mindsets, has done beautiful experiments on stress, showing that if you watch a short video about stress, and you learn all the terrible things that stress can do to your cognition, your sleep, and your wellbeing, well, th- indeed that happens. And that if you watch a short video about how stress can be performance-enhancing by sharpening your mental acuity, your access to particular memory stores, et cetera, that indeed that happens, so-called belief effects. Why belief effects and not placebo effects? Well, placebo effects tend to be more general. Belief effects tend to be around specific types of information. But the placebo effect has recently been shown to extend to a dose-dependent placebo effect. One of the more remarkable papers I think published in the last few years, most people are unaware of, I talked about this in a journal club episode of the Human Lab Podcast with the one and only Peter Attia, described a paper where people took either zero, I believe it was .25 milligrams, half a milligram, or a gram of nicotine, which is known to be a cognitive enhancer. Please don't smoke, dip, huff, or snuff nicotine. That's cancerous in those forms, but ... And taking nicotine can increase blood pressure, vasoconstriction, et cetera, but nicotine is a cognitive enhancer. It is a cognitive enhancer. And I can't help but tell you one story about this, b- before I get back to placebo effect. Don't worry, I always make my way back. Now you can see why living with me as a child was so challenging. Um, nicotine, I was told by a very, very famous Nobel laureate member of the neuroscience community, because I visited his office, I won't tell you who it is, at Columbia University, I met with him, and he was telling me about what he studies, but I noticed he chewed no fewer than six pieces of Nicorette during the course of that conversation, and I had to just stop him at one point and say, "Why are you consuming all this nicotine?" And he said, "Well, it's what's going to allow me to stave off Parkinson's and Alzheimer's, of course, and I don't wanna smoke." And I said, "Really?" And he said, "Yeah, there's some evidence that keeping levels of neuromodulators like dopamine and acetylcholine elevated despite the increases in blood pressure that are caused by consuming nicotine may indeed offset Parkinson's and Alzheimer's." I'm not telling you this as a clinical trial, I'm telling you this as anecdata. He is a Nobel Prize winner. He's still very, very sharp in his 80s. The point here is that in a study of nicotine and cognition, where people's cognition is indeed enhanced by nicotine, everybody knows that and agrees upon that, people who were told they had a higher dose of nicotine performed better in this cognitive task when in fact they consumed zero. And people who performed moderately, who were then told that they had consumed a higher dose of nicotine, performed better than those that simply consumed the moderate dose and were told they had a moderate dose. In other words, everyone gets the same dose, either zero or moderate, but depending on what you're told, your performance changes accordingly, and that's cool. But what's really cool about the study is they actually recorded from brain centers of these individuals and the levels of activity in particular areas of the brain that are relevant for cognition changed according to what the people believe. So there you go. Placebo effect is changing neural activity. It's not all just through what you think is happening. What you think is happening is the reflection of neural activity, and then you go, "Well, of course." But I think it's an important study, so I believe in the placebo effect, and it is dose dependent, and th- that raises all sorts of scary concerns about the placebo effect, but it's also pretty darn cool, because what it means is that our belief system, including our understanding of the mechanisms that are likely driving certain effects of drugs, or protocols, or what have you, is going to play a powerful role in whether or not we get the effect that we want. And perhaps that's the most important thing, provided that you're going about it safely. "How do I enter the rest and digest state and exit my constant fight or flight state?" Well, the fastest way is gonna be physiological sighs, probably repeated two or three times in a row. If you don't experience that the first time, the second would be to combine that with panoramic vision. I must say, and I don't wanna sound like a, like a repeating record here, but there are certain things that if we're not doing on a regular basis, our nervous system is just going to idle at a higher, let's just call it autonomic R- RPM, which is not, you know, r- real science language, but if you've ever felt, you know, wired and tired from lack of sleep, you know what this is about. The key thing is to get enough sleep each night, you know, so much so that I think we can safely say that stress is not bad for us provided you sleep well at night.Now, the challenge is for most people, including myself, if you stress a lot, sleep doesn't come easily or you wake from sleep in the middle of the night. And here again, is where zero-cost behavioral protocols are truly, in my opinion, unless there's some dire clinical need, the most effective and best practice. And this non-sleep deep rest which, by the way, is indeed a renaming or a partial renaming of Yoga Nidra, which stands for yoga sleep, and again, I have tremendous reverence for the yogic traditions. It's just that I had to make a decision a few years ago when I'd been introduced to Yoga Nidra in 2015. I was down at a trauma treatment center and addiction treatment center in Florida run by a friend of mine, essentially ab- observing what they were doing with these addicts that couldn't recover, no matter what their effort, and they were able to recover, to get sober and stay sober, and people were getting over other sorts of traumas through the use of many protocols, of course, talk therapy, et cetera. But they would start their day with 30 minutes to an hour of Yoga Nidra. And I thought, "What's Yoga Nidra?" Ex- learned it's yoga sleep, you lie down, you do a self-directed relaxation, it also involves intentions, et cetera. And I thought, "This is really powerful," and I spent a lot of time in my laboratory working on it and understanding it, and there are other studies as well that now explain how these states of keeping the mind active while the body is still, as a self-directed practice, is immensely powerful for a number of reasons. And the reason I decided to call it Non-Sleep Deep Rest, NSDR, was not to rob it of the official name of Yoga Nidra but because unfortunately, unfortunately, names like Yoga Nidra or proprietary names or thing... or when we name protocols after people, it acts as a separator. It often deters people from trying things because it sounds esoteric, so I went with a description of the thing that relates to what the thing is supposed to do, Non-Sleep Deep Rest, or what it's all about. So, um, you know, I actively avoided calling it Huberman Breathing, um, or something like that because that's not my interest. My interest is in people using these tools, and I have taken some heat for that one. Um, I'm not interested in... it was not an attempt to appropriate something. It was really an attempt to just try and distribute valuable tools because I see a lot of suffering, and it seems like a useful thing to do. So, I would encourage anyone that feels like they enter a stressed state too much to learn self-directed relaxation first and foremost, so do NSDR anywhere from three to five times a week, 10 minutes a day, as a zero-cost tool, as a way to be able to better access better sleep at night, and then if the fight or flight state persists, then, of course, things like physiological signs, et cetera, um, should be incorporated, and then of course, of course, of course, I believe in modern medicine. There are excellent pharmaceutical tools, prescription drugs that can be used for that. But, of course, there's the intermediate stuff, things like theanine and magnesium that, you know, for all the world, can be useful in some context, but they're not the be-all, end-all. You know, I- I, as much as I might reference supplements on the podcast from time to time, I don't think they're the place to start. I think one should always use behavioral tools first. And I've said this many times before, um, but, uh, I think it's worth saying again. "Our muscles need rest days from the gym in order to grow back stronger." Yes, definitely true. Um, "Is the brain designed to be consistently learning and developing or devel- does it need periods of rest from consuming new information? Or is the rest when we sleep?" Great questions. Thank you, Timothy. Um, yes indeed, our muscles get stronger, grow after a proper stimulus is apr- applied to them in the time after we provide that stimulus, which typically is resistance. But since not everyone's interested in that, it's also the case that an endurance adaptation occurs after we embark on the run, the hike, the swim, et cetera. There's something kind of interesting, and I just wanna take a moment just, um, mention that there's something kind of interesting about resistance training is that it's the one form of training that, because of the enhanced blood flow to the muscles while we do it, gives us a window into what the adaptation might look like once it occurs if we allow proper rest. Whereas with endurance training, it's very different, right? You go further and/or you run up a hill until your legs burn and you wanna vomit up a lung, and then the next time you do it, you don't feel quite as bad, right? The adaptation occurs, of course, in a very similar way to resistance training, different mechanisms, but there's a delay in adaptation and you get better. It's just that re- with resistance training you can kind of sense the change before the change occurs because of the enhanced blood flow of the muscles. With endurance training, you sense the limit of your ability and then you exceed that limit subsequently. Now, in terms of cognitive learning, the same thing is basically true. If you wanna get really technical about it, the computational biology, the modeling of this says that if you wanna learn something, probably setting the difficulty of what you're trying to learn to about 85% correct trials, 15% error trials is probably ideal. What does that mean? It means if you're trying to learn a new piano piece, you know, or you're trying to teach that to a child, if they're not starting from scratch, let them play something that they know pretty well and then introduce a small percentage, maybe 10 to 15, maybe 20%, you don't have to be exact about this, of novel material that's hard for them to learn. But, yes, it is the focused, deliberate attempt to learn something that creates that sense of underlying agitation that is the trigger, the stimulus for neuroplasticity. This makes sense if you could complete something, if you could do something, a scale on, of music, a physical task, speaking a new language, if you could do that, why would your nervous system ever change, and how does your nervous system know if it's supposed to change? Right? Your nervous system doesn't know successful trial versus failure trial.Right? I've tried many times to learn other languages, and I'm, you know, modestly terrible at Spanish. But if I were to try and get better, my nervous system doesn't know when I'm failing. It has no idea. What it knows is the release of certain neuromodulators, namely adrenaline and norepinephrine, and a few others as well, that are associated with the underlying agitation of like, "Oh, I'm failing at this. I'm not able to remember that Spanish class 'cause I didn't attend in high school, and this is really difficult." And that agitation, the frustration is the stimulus, but when we say frustration, it's the neurochemicals that, when they bathe the surrounding neurons, those neurons go, "Oh, something needs to change for next time." And lo and behold, the stimulus for neuroplasticity has occurred. But the actual rewiring of the neurons, either the improvement or the reduction in the strength of synapses, of connections between neurons, and in rare instances, the addition of new neurons for neuroplasticity occurs, yes, when we sleep, in states of deep rest or non-sleep deep rest, although there's less data to support that. But the actual rewiring occurs away from the stimulus. So, there's really two important principles here. One is that agitation and stress and the neurochemicals that underlie agitation and stress, that is the stimulus for learning. And goodness, do I wish they had taught me that in school. I mean, they taught me all sorts of things in school, but they didn't teach me that. They didn't teach me the physiological side. Lord knows I would have done better in life if I had a couple of those tools. Instead, they told me, "Look, you know, if you drive drunk, you could die." That was good information, but they didn't tell us about all the other stuff. So, I wish they told us about the stimulus and rest thing, and somehow they have permission to talk about the rest. All right. What's my take on hallucinogens (laughs) ? Goodness gracious. My take on hallucinogens is, um, I've taken 'em, um, clearly. Um, well, here's the real story on hallucinogens. First of all, um, I'm very open about most everything I've done, you know, um, try and keep context appropriate. But, um, I had the unfortunate experience of taking LSD and psilocybin when I was all too young, and those were bad experiences. Some of them were bad in the moment. Some of them were bad after the moment. It is something I do not recommend, and I'm not saying that to be politically correct. I'm not saying that because it's true. The reality is that being a child, an adolescent, or a teenager is a psychedelic experience. (laughs) And your brain is still wiring up in all sorts of interesting ways, and everything seems chaotic. And even if you're one of those rare kids that seems to have everything rode up appropriately, you don't want to throw massive amounts of neuromodulators in there haphazardly and start tampering with the wiring. That's my deep belief. Okay? You can... That's my deep belief. However, it does appear that at least for adults who are not suffering from particular psychiatric challenges, namely forms of psychosis, right? This is real. I mean, 1 in 100 people experiences schizophrenic symptoms, et cetera. It's a very high number if you think about it. Um, certain forms of bipolar, depression, that the clinical trials on psychedelics, and here I'm assuming when you say hallucinogens you're referring to psychedelics, are very, very compelling. The psychiatric community is now being forced to look at these data because the data are very compelling. What do we know about these data? And yes, I've participated in two such clinical trials, one on high dose psilocybin, high dose meaning more than two grams taken twice. By the way, this is with the support of medically trained therapists and the use of psychedelics such as psilocybin, mostly psilocybin, not so much LSD. Do you know why most of the trials are on psilocybin and not LSD? I do, but I'm curious if, you know, it's not... (Inaudible) . What's that? It's too long. LSD is too long. That's right. That people need to go home. People need to go home. The technicians need to... And LSD is a long ride. It's a long ride. So, the thing about psilocybin is that the, you know, the sort of journey, the trip is, you know, somewhere on the order of anywhere from, you know, three to seven hours, which can fit into a reasonable workday for a technician clinician, um, and LSD can be many, many hours longer. The kind of Mount Everest of psychedelics, which is under investigation by a colleague of mine at Stanford School of Medicine, Nolan Williams, is Ibogaine, Iboga, which is 22 hours long. It has cardiac effects. This is not something to get cavalier with. This is something only to be done in a clinical context with medical experts there. And Iboga is very interesting from what I'm told. I have not participated in any Iboga trial. Iboga allows for or induces a state in which you do not hallucinate at all with eyes open, but the moment you go eyes closed, you get a high-resolution accurate picture of prior events in your life, but you have agency, you have volition inside of those pictures, and you're able to change your behavior and re-sculpt your relationship to those experiences. Like, wow. And the state of Kentucky and California recently... Uh, excuse me, the state of Kentucky in the United States. Thank goodness Kentucky isn't inside of California. That would be civil war. (laughs) The state of Kentucky recently took the $40 million settlement from the opioid thing, right? You've all heard about that, the opioid crisis, and applied that money to Iboga trials. So, this stuff is happening. This stuff is really happening now in the US. In any event, psilocybin...These two sessions, medically supported, two sessions, um, has been shown to be pretty effective in the treatment of major depression. Um, not completely effective. Sometimes there's adverse outcomes, but far more effective than the other ph- pharmaceutical treatments that it's been compared to, so that's interesting. And psilocybin is serotonin. If you look at the structure of psilocybin, it looks like serotonin, so what we're talking about is a massive dose of serotonin, and psilocybin appears to bind near-selectively to a particular serotonin receptor and the outcome seems to be enhanced or more l- more broad connectivity between brain areas that normally are not communicating with one another. Probably not the growth of new connections, but the, let's say, the unveiling of the ability for certain brain areas to communicate with one another, whereas they couldn't prior. Different ways of thinking about the same problems, which is logically sound if you think about ways to deal with depression. Depression is characterized by a number of things, of course, but one of the hallmark features of depression in addition to sleep challenges is a lack of positive anticipation of the future, and it does seem that these macrodose psilocybin trials are helpful for that. Turns out that the microdosing of psilocybin has not been shown to be terribly effective, which is not to say it isn't, but the trials don't support that, although there aren't many trials of that yet. So it appears, you know, if you had to pick between micro and macro dosing, go macro. Um, but be careful, um, go c- be careful and, and set and setting is important. Safety is important and certainly not for children. And as long as, uh, and, or adolescents or teenagers, I really again wanna, wanna reemphasize that. The, the other thing is as long as we're talking about psychedelics and hallucinogens we should probably just touch on MDMA for a moment. First of all, MDMA, ecstasy, um, has a number of challenges or p- potential problems that need to be highlighted. First of all, um, contaminants, you know, we have a fentanyl crisis in the US, so contaminants, so purity is essential. Second of all, it is methylenedioxymethamphetamine, and the methamphetamine part often gets people thinking, like, "Whoa." It seems, however, that the inclusion of the methylenedioxy component increases serotonin dramatically and it is the increase in serotonin perhaps, or at least it's now thought, in addition to the increase in dopamine caused by the methamphetamine component combined that provides some sort of neuroprotective effect. The early reports that MDMA, ecstasy, is neurotoxic, quote-unquote, "puts holes in your brain," was flawed by... and indeed that paper was retracted. The researchers did that study in earnest but then later discovered that when they reached for the MDMA on the shelf, they actually grabbed the methamphetamine, but the news agencies didn't report that retraction. Now, our best evidence that MDMA taken in the appropriate clinically supported context can act as an empathogen, can help people develop empathy for themselves and help relieve trauma, and indeed the clinical trials show that at the proper dosing and the proper frequency with the proper support there's up to 60% and as high as 67% remission of PTSD. Remarkable. With support, okay? Not just taking Molly and, like, dancing in the desert. We're talking about, we're talking about in the eye mask, we're talking about going inward, we're talking about relaying your experience, we're talking about talking about the challenging experience or experiences with someone who's qualified to help you deal with all of that, et cetera, and someone to drive you home 'cause you feel like a puddle afterwards, talking about all of that. We're not talking about eye gazing with your partner, telling them how much you love them. We're talking about empathy for self, love for self, which is a concept that frankly I've often struggled with. I've thought, you know, people would say, "You gotta love yourself." I'm like, "What is that? Like, what is that?" I love my bulldog, I love my friends, I love cuttlefish, but, like, what is that? And I think through the use of MDMA you can, there seems to be this ability to develop empathogenic states to yourself but of course the reason for the clinical trials insisting that people stay in the eye mask and communicate their experience, maybe popping out of it every once in a while and talking with somebody in a trusted sor- a trusted person and in a way that can be helpful towards dealing with the trauma is that the problem with having that much serotonin and that much dopamine in your system is that you can become empathic toward anything. So we've all known people that take MDMA listen to a particular soundtrack and they're like, "I'm gonna become a musician. I love music." And again, I'm not recommending anyone do MDMA, but in recent years I've really changed my stance on psychedelics. Five years ago, 10 years ago, I never would have had this discussion, certainly not with a microphone in front of my face, anything being recorded. Would've worried about losing my job at Stanford or elsewhere. But we now have many laboratories at Stanford and elsewhere that are doing work that is federally funded on these compounds, and if you think about these compounds while they have been used recreationally are simply ways to adjust levels of neuromodulators in the brain, serotonin, dopamine, et cetera. That's really all they are, although they do it very potently and therefore caution needs to be applied. And as long as we're on that topic, I should mention that ketamine, everyone's excited about ketamine. When I was growing up, I was taught that there's a compound that's really dangerous, it's called PCP, phencyclidine. They are the same compound. They don't tell you this. Ketamine and PCP, same thing, and I learned about PCP as the compound that was gonna make criminals, like, punch light poles and beat up 12 cops and, yeah, I watched too much CHiPs when I was growing up. For those of you o- old enough to remember it was, like, Ponch and Jon, they were riding the motorcycles with the shorts. My sister watched it too but for completely different reasons. So PCP was, like, this d- demonized drug, but ketamine and all this stuff about ketamine...... is now legal in the US, I don't know its status here in Sydney, so I'll see if I get arrested on the way out. But, you know, ketamine is potentially addictive, uh, people talk about the K-hole, et cetera. Weird name, by the way. Um, the whole business with ketamine is that again, it's a potent MDMA, N-methyl-D-aspartate blocker, which blocks neuroplasticity in the short term, it expands it in the long term. So, the way to think about these compounds, these drugs, is by way of their mechanism, and so it should be no surprise that they're able to induce neuroplasticity, but the goal is not plasticity. This is very, very important. The goal is not plasticity. The goal is plasticity directed toward a particular positive outcome. Any time you have plasticity, you have the potential for maladaptive plasticity as well, and so that's an additional cautionary note. As I often say on the podcast, I don't say that just to protect me, although I am a little bit worried now about what I just said over the last five minutes. (laughs)
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