Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth

In this episode of Huberman Lab Essentials, my guest is Dr. Karl Deisseroth, M. D., Ph. D., a clinical psychiatrist and professor of bioengineering and of psychiatry and behavioral sciences at Stanford University. We discuss his experiences as a clinician treating complex psychiatric conditions and his lab’s pioneering work in developing transformative therapies for mental illness. He explains the complexities of mental illness and how emerging technologies—such as optogenetics and brain-machine interfaces—could revolutionize care. We also explore promising new therapies, including psychedelics and MDMA, for conditions like depression and PTSD. Read the episode show notes at hubermanlab.com. Huberman Lab Essentials are short episodes focused on essential science and protocol takeaways from past full-length Huberman Lab episodes. Watch or listen to the full-length episode at ⁠hubermanlab.com⁠. Thank you to our sponsors AG1: https://drinkag1.com/huberman David: https://davidprotein.com/huberman Eight Sleep: https://eightsleep.com/huberman Timestamps 00:00:00 Karl Deisseroth; Neurology vs Psychiatry 00:01:36 Speech; Blood Test?; Seeking Help 00:04:20 Feelings, Jargon; Psychiatric Treatment 00:09:40 Sponsor: David 00:10:55 Future Treatment; Vagus Nerve Stimulation, Depression, Optogenetics 00:19:40 Brain-Machine Interfaces 00:20:53 Sponsor: Eight Sleep 00:23:00 ADHD Symptoms, Lifestyle, Technology 00:29:34 Psychedelics, Depression Treatment, Risks 00:35:43 Sponsor: AG1 00:37:30 MDMA (Ecstasy), Trauma & Post-Traumatic Stress Disorder (PTSD) Treatment 00:40:33 Projections: A Story of Human Emotions Book, Optimism Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

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

• 0:00Speaker 00

  Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. And now, my conversation with Dr. Carl Diceroff. Well, thanks for being here.

• 0:17Speaker 01

  Thanks for having me.

• 0:17Speaker 00

  So for people that might not be so familiar with the fields of neuroscience, et cetera, what is the difference between neurology and psychiatry?

• 0:26Speaker 01

  Psychiatry focuses on disorders where we can't see something that's physically wrong, where we don't have a measurable, where there's no blood test that makes the diagnosis. There's no brain scan that tells us this is schizophrenia, this is depression for an individual patient. And so psychiatry is much more mysterious. And the only tools we have are words. Neurologists are fantastic physicians. They see the stroke on brain scans. They see the seizure and the pre-seizure activity with an EEG. And they can measure and treat based on those measurables. In psychiatry, we have a harder job. We use words.

• 1:11Speaker 01

  We have rating scales for symptoms. We can measure depression and autism with rating scales, but those are words still. And ultimately, that's what psychiatry is built around. It's an odd situation because we've got the most complex, beautiful, mysterious, incredibly engineered object in the universe. And yet, all we have are words to find our way in.

• 1:36Speaker 00

  So do you find that if a patient is very verbal or hyperverbal, that you have an easier time diagnosing them? As opposed to somebody who's more quiet and reserved? Or is, I can imagine the opposite might be true as well?

• 1:51Speaker 01

  Well, because we only have words, you've put your finger on a key point. If they don't speak that much, in principle, it's harder. The lack of speech can be a symptom. We can see that in depression. We can see that in the negative symptoms of schizophrenia. We can see that in autism. Sometimes by itself, that is a symptom of reduced speech. But ultimately, you do need something. You need some words to help guide you. And that, in fact, and there's challenges that I can tell you about, where patients with depression, who are so depressed they can't speak. That makes it a bit of a challenge to distinguish depression from some of the other reasons they might not be speaking. And this is a sort of the art and the science of psychiatry.

• 2:31Speaker 00

  Do you think we will ever have a blood test for depression, or schizophrenia, or autism? And would that be a good or a bad thing?

• 2:39Speaker 01

  I think ultimately, there will be quantitative tests. Already, efforts are being made to look at certain rhythms in the brain using external EEGs to look at brainwaves effectively. But ultimately, what's going on in the brain in psychiatric disease is physical. And it's due to the circuits and the connections and the projections in the brain that are not working as they would in a typical situation. And I do think we'll have those measurables at some point. Could it be abused or misused? Certainly, but that's, I think, true for all of medicine.

• 3:15Speaker 00

  I want to know, and I'm sure there are several, but what do you see as the biggest challenge facing psychiatry and the treatment of mental illness today?

• 3:25Speaker 01

  I think we have, we're making progress on what the biggest challenge is, which I think there's still such a strong stigma for psychiatric disease that patients often don't come to us. And they feel that they should be able to handle this on their own. And that can slow treatment. It can lead to worsening symptoms. We know, for example, patients who have untreated anxiety issues, if you go for a year or more with a serious untreated anxiety issue, that can convert to depression. You can add another problem on top of the anxiety. And so it would be, you know, why do people not come for treatment?

• 4:10Speaker 01

  They feel like this is something they should be able to master on their own, which can be true, but usually, some help is a good thing.

• 4:21Speaker 00

  That raises a question related to something I heard you say many years ago at a lecture, which was that, um, this was a scientific lecture and you said, you know, "We don't know how other people feel. Most of the time, we don't even really know how we feel." Maybe you could elaborate on that a little bit and the, the dearth of, of ways that we, we have to talk about feelings. I mean, there are so many words. I don't know how many, but I'm guessing there are more than a dozen words to describe the state that I call sadness. But as far as I understand, we don't have any way of comparing that in a, in a real, objective sense. So how, as a psychiatrist, when your job is to use words to diagnose, words of the patient to diagnose, do you maneuver around that?

• 5:06Speaker 00

  And, and what is this landscape that we call feelings or emotions?

• 5:10Speaker 01

  This is, uh, really interesting. Uh, people, here we have a, there's a tension between the words that we've built up in the clinic that mean something to the, to the physicians. And then there's the colloquial use of words that may not be the same. And so that's the first level we have to sort out. When someone says, you know, "I'm, I'm depressed", uh, what exactly do they mean by that? Uh, that may be different from, from what we're talking about in terms of depression. So part of psychiatry is to get beyond that word and to get into how they're actually feeling. Get, get rid of the, the jargon and get to real world examples of, of how they're feeling. So, you know, how do you, what, how much do you look forward into the future?

• 5:54Speaker 01

  How much, uh, hope do you have? How much planning are you doing for the future? So these, here now you're getting into actual things you can talk about that are unambiguous. If someone says, "Yeah, I, I can't even, I can't even think about tomorrow. I, I'm not, I don't see how I'm going to get to tomorrow." That, that's a nice, precise thing that, you know, it's, it's sad, it's tragic, but, but it's also, that means something and we know what that means. That's the hopelessness symptom of depression. And that is what I try to do when I do a psychiatric interview. I try to get past the jargon and get to what's actually happening in the patient's life and in their mind. But as you say, ultimately, you know, this shows up across.

• 6:35Speaker 01

  I, I, I address this issue every day in my life, whether it's in the lab where we're looking at animals, whether fish or mice or rats and studying their behavior. Or when I'm in a conversation with just a friend or a colleague, or when I'm talking to a patient, I never really know what's going on inside the mind of the other person. I get, I get some feedback, I get words, I get behaviors, I get actions, but I never really know.

• 7:04Speaker 00

  Are there any very good treatments for psychiatric disease? Meaning are there currently any pills, potions, forms of communication that reliably work every time? Or work in most patients? And could you give a couple of examples of great successes of psychiatry if they exist?

• 7:22Speaker 01

  Yes. And psychiatry, despite the depths of our, the mystery we struggle with, many of our treatments are actually, you know, we're, we may be doing better than some other specialties in terms of actually causing, you know, therapeutic benefit for patients. We do help patients, you know, patients who suffer from, by the way, both medications and talk therapy have been shown to be extremely effective in many cases. For example, people with panic disorder. Cognitive behavioral therapy, just working with words, helping people identify the early signs of when they're starting to move toward a panic attack. What are the cognitions that are happening? You can train people to derail that and you can very potently treat panic disorder that way.

• 8:04Speaker 01

  There are many psychiatric medications that are very effective for the conditions that they're treating. Antipsychotic medications, they have side effects, but boy, do they work. They really can clear up auditory hallucinations, the paranoia. And then, you know, this is a frustrating and yet heartening aspect of psychiatry. There are treatments like electroconvulsive, electroconvulsive therapy, which is where, you know, it's extremely effective for depression. We have patients who, nothing else works for them.

• 8:36Speaker 01

  Where they can't tolerate medications and you can administer under a very safe, controlled condition where the patient's body is not moving, they're put into a very safe situation where the body doesn't move or seize, it's just an internal process that's triggered in the brain. This is an extraordinarily effective treatment for treatment-resistant depression. At the same time, I find it, as heartening as it is to see patients respond to this with, who have severe depression, I'm also frustrated by it. Why, why can't we do something more precise than, than this for these very severe cases? In all of these cases, though, in psychiatry, the frustrating thing is that we don't have the level of

• 9:18Speaker 01

  understanding that a cardiologist has in thinking about the heart. You know, the heart is, we now know, it's a pump, it's pumping blood, and so you can look at everything about how it's working or not working in terms of that frame. It's clearly a pump. We don't really have that level of, what, what is the circuit really there for in psychiatry?

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• 10:55Speaker 00

  What are the pieces that are going to be required to cure autism, cure Parkinson's, cure schizophrenia? I would imagine there are several elements and bins here. Understanding that the natural biology, understanding what the activity patterns are, how to modify those. Maybe you could just tell us what you think. What is the bento box of the perfect cure?

• 11:20Speaker 01

  Yeah. I think the first thing we need is understanding what is the element in the brain that's analogous to the pumping heart? When we think about the symptoms of depression, that's maybe, you know, we think about motivation and dopamine neurons. And so then that turns our attention as neuroscientists. We think, okay, let's think about the parts of the brain that are involved in dealing with merging complex data streams that are very high in bit rate that need to be fused together into a unitary concept. And that starts to guide us and maybe we can, and we know other animals are social in their own way and we can study those animals. And so that there's, that's how I think about it. There's hope for the future.

• 12:03Speaker 01

  Thinking about the symptoms as an engineer might and trying to identify the circuits that are likely working to make this typical behavior happen. And that will help us understand how it becomes atypical.

• 12:16Speaker 00

  We need to know the circuits. We need to know the cells in the various brain regions and portions of the body and how they connect to one another and what the patterns of activity are under a normal quote unquote, healthy interaction.

• 12:30Speaker 01

  Yeah.

• 12:32Speaker 00

  If we understand that, then it seems that the next step, which of course could be carried out in parallel, right? That work can be done alongside work where various elements within those circuits are tweaked just right, like the tuning of a piano in the subtle way, or maybe even like the replacement of a whole set of keys if the piano is lacking keys, so to speak. In 2015, there was this, what I thought was a very nice article published in The New Yorker, describing your work and the current state of your work in the laboratory in the clinic, and an interaction with a patient. So this, as I recall, a woman who was severely depressed. And you reported in that article some of the discussion with this patient,

• 13:17Speaker 00

  and then in real time, increase the activation of the so-called vagus nerve, this 10th cranial nerve that extends out of the skull and innervates many of the viscera and body. What is the potential for channelrhodopsins or related types of algae engineering to be used to manipulate the vagus? Because I believe in that instance, it wasn't channelrhodopsin stimulation, it was electrical stimulation, right? Or to manipulate, for instance, a very small localized region of the brain? Let me frame that a little bit differently, in light of what we were talking about a couple of minutes ago. My understanding is that if somebody has severe depression and they take any number of the available pharmaceutical agents that are out there,

• 14:02Speaker 00

  SSRI, serotonin, or JIC agents, increased dopamine, increased whatever, that sometimes they experience relief, but there are often serious side effects. Sometimes they don't experience relief, but as I understand it, channelrhodopsins and their related technology in principle would allow you to turn on or off the specific regions of the brain that lead to the depressive symptoms, or maybe you turn up a happiness circuit, or a positive anticipation circuit. Where are we at now in terms of bringing this technology to the nervous system? And let's start with the body, and then move into the skull.

• 14:41Speaker 01

  Yeah. So starting with the body is a good example because it highlights the opportunity and how far we have to go. So let's take this example of vagus nerve stimulation. So the vagus nerve, it's the 10th cranial nerve, it comes from the brain, it goes down, it innervates the heart, it innervates the gut. By innervate, I mean it sends little connections down to help guide what happens in these organs, in the abdomen and chest.

• 15:08Speaker 01

  It also collects information back and and there's information coming back from all those organs that go also go through this vagus nerve, the 10th cranial nerve back to the brain. And so this is somewhat of a of a of a superhighway to the brain then was the idea. And maybe the idea is maybe we could put a little cuff, a little electrical device around the vagus nerve itself, so a way of getting into the brain without putting something physical into the brain.

• 15:35Speaker 00

  And why the vagus? I mean, it's there, but and it's accessible.

• 15:38Speaker 01

  That's the reason.

• 15:39Speaker 00

  That's the reason?

• 15:40Speaker 01

  That's the reason, yes.

• 15:41Speaker 00

  Really?

• 15:42Speaker 01

  Yeah.

• 15:43Speaker 00

  You're not kidding?

• 15:44Speaker 01

  I'm not kidding.

• 15:45Speaker 00

  So stimulating the vagus to treat depression simply because it's accessible?

• 15:47Speaker 01

  It started as actually as an epilepsy treatment and it can help with epilepsy, but the vagus nerve lands on a particular spot in the brain called the solitary tract nucleus, which is just one synapse away from the serotonin and dopamine and the norepinephrine.

• 16:03Speaker 00

  So there's a link to chemical systems in the brain that make it a rational choice?

• 16:06Speaker 01

  Yes, it's not it's not irrational, but I can tell you that even if that were not true, the same thing would have been tried.

• 16:12Speaker 00

  You guys would have done it anyway.

• 16:15Speaker 01

  Because it's accessible.

• 16:16Speaker 00

  I see. How do you think it's working when it does work? Is it triggering the activation of neurons that release more serotonin or dopamine?

• 16:22Speaker 01

  It could be, but I would say we don't have evidence for for that. And so I just don't know. But what is clear is that it's dose limited in how high and strongly we can stimulate. And why? It's because it's an electrode and it's stimulating everything nearby. And when you turn on the vagus nerve stimulator, the voice, patient's voice becomes strangulated and hoarse. They can have trouble swallowing, they can have trouble speaking for sure, even some trouble breathing, because everything in the neck, every electrically responsive cell and projection in the neck is being affected by this electrode. And so you can go up just so far with the intensity and then you have to stop.

• 17:03Speaker 01

  So, you know, to your initial question, could a more precise stimulation method like optogenetics help in this setting? In principle, it could because that would if you would target the light sensitivity to just the right kind of cell.

• 17:19Speaker 01

  Let's say cell X that goes from point A to point B that you know causes symptom relief of a particular kind, then you're in business. You can have that be the only cell that's light sensitive. You're not going to affect any of the other cells, the larynx and the pharynx and the projections passing through. So that's the hope, that's the opportunity. The problem is that we don't yet have that level of specific knowledge. We don't know, okay, it's the cell starting in point A going to point B that relieves this particular symptom.

• 17:47Speaker 00

  We want to fix this key on the piano.

• 17:49Speaker 01

  Yeah.

• 17:49Speaker 00

  I'm imagining a little tiny, um, blue light emitting, um, thing, object that's a little bigger than a clump of cells, or maybe about the size of a clump of cells. So we're talking about a little tiny stamp, each edge half a millimeter in size. I could imagine that being put under my skin.

• 18:08Speaker 01

  Yeah.

• 18:09Speaker 00

  And then I would, what I'd hit an app on my phone and I'd say, I'd say, Dr. Deisseroth, I'm not feeling great today. Can I increase the stimulation? And you say, go for it. And then I ramp it up. Is that how it would go?

• 18:20Speaker 01

  I mean, that's effectively what we already do with the vagus nerve stimulation. The, the doctor in this case, and I, I have this in some of my patients in the clinic. I do vagus nerve stimulation. I talk to them, I say, how I, I go through the symptoms. I, I use the psychiatric interview to elicit their internal states. And then I have a radio frequency controller that I can dial in.

• 18:39Speaker 00

  Right there in real time.

• 18:40Speaker 01

  Right there in real time.

• 18:41Speaker 00

  You're holding the remote control essentially to their brain, although it's remote, remote control.

• 18:45Speaker 01

  Through a couple of steps, but yeah.

• 18:46Speaker 00

  Yeah.

• 18:47Speaker 01

  Yeah. And I can, I can turn up, I can turn up the frequency, I can turn up the intensity, uh, all with the radio frequency and, uh, uh, control. And then it's, it's reprogrammed or redosed. And then the patient can, can then leave at this altered dose. In most patients, I don't expect an immediate mood change. What I do is I increase the, the dose until, uh, uh, a next level up while asking the patient for side effects. Can you still breathe okay? Can you still swallow okay? And I can hear their voice as well and I can get a sense.

• 19:18Speaker 00

  And you're looking at their face.

• 19:19Speaker 01

  And I'm looking at their face.

• 19:20Speaker 00

  Yeah.

• 19:20Speaker 01

  And so I can get a sense, is there a, uh, am I in a, still in a safe side effect regime? And I, and, and, and then, you know, I, I, I stop at a particular point that looks safe and then patient goes home. Comes back a month later and I get the report on how things were over that month.

• 19:37Andrew D. Huberman?

  That's very exciting. What are your thoughts about brain machine interface as something that's been happening for a long time now? Devices, little probes are going to stimulate different patterns of activity and ensembles of neurons.

• 19:51Speaker 01

  First of all, it's an amazing scientific discovery approach. As you mentioned, we and others here at Stanford are using electrodes, collecting information from tens of thousands of neurons. Even separate from the Neuralink work, as you point out, many people have been doing this in humans as well as in non-human primates. And this is pretty powerful. It's important. This will let us understand what's going on in the brain in psychiatric disease and neurological disease. It will give us ideas for treatment. I see that as something that will be part of psychiatry in the long run. Already with deep brain stimulation approaches, we can help people with psychiatric disorders.

• 20:37Speaker 01

  And that's putting just a single electrode, not even a complex, you know, closed loop system where you're both playing in and getting information back. Even just a single stimulation electrode in the brain can help people with OCD, for example, quite powerfully.

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• 23:00Speaker 00

  One of the questions I get asked a lot is about ADHD and attention deficit of various kinds. I have the hunch that one reason I get asked so often is that people are feeling really distracted and challenged in funneling their attention and their behavior. But, and there are a number of reasons for that, of course. But what is true ADHD? And what does it look like? What can be done for it? And what if any role for channel options or these downstream technologies that you're developing? What do they, what do they offer for people that suffer from ADHD or have a family member that suffers from ADHD?

• 23:45Speaker 01

  This is a pretty interesting branch of psychiatry. There's no question that people have been helped by the treatments. There's, you know, active debate over, you know, what fraction of people who have these symptoms can or should be treated.

• 24:02Speaker 00

  This is typically Adderall or stimulants of some kind.

• 24:05Speaker 01

  For example, stimulants, that's right. So ADHD, as its name suggests, it has symptoms of, it can have either a hyperactive state or an inattentive state. And those can be completely separate from each other. You could have a patient who effectively is not hyperactive at all, but can't remain focused on the what's going on around them.

• 24:29Speaker 00

  So their body can be still, but their mind is darting around.

• 24:33Speaker 01

  That's right.

• 24:33Speaker 00

  Or they can be very hyperactive with their body.

• 24:35Speaker 01

  Yeah, it happens both ways.

• 24:36Speaker 00

  Probably rarely is somebody hyperactive with their body, but their mind is still.

• 24:39Speaker 01

  I notice, I have to think complex, abstract thoughts. I notice I have to be very still. So my body has to be almost completely unmoving for me to think very abstractly and deeply. Other people are different. Some people, when they're running, they get their best thoughts. I can't even imagine that. My brain does not work that way at all. I have to be totally motionless, which is kind of interesting.

• 25:00Speaker 00

  How do you go about that?

• 25:01Speaker 01

  I sit much like this. You know, I try to have time in each day where I am literally sitting almost in this position, but without distraction and thinking. And so it's kind of a, it's almost meditative in some ways, except it's not true meditation. But I am thinking while not moving.

• 25:24Speaker 00

  You're trying to structure your thoughts in that time. Interesting.

• 25:28Speaker 01

  So, but everybody, as you say, is very different. And so with ADHD, you have, the key thing is we want to make sure that this is present across different domains of life, school and home, to show that it really is a pervasive pattern and not something specific to, you know, the teacher or the home situation or something. And then you can help patients. It's interesting that ADHD is one of those disorders where people are trying to work on quantitative EEG-based diagnoses. And so there's some progress toward making up a diagnosis with looking at particular externally detectable brainwave rhythms.

• 26:06Speaker 00

  So skull cap with some electrodes that don't penetrate the skull?

• 26:09Speaker 01

  That's right.

• 26:10Speaker 00

  And this can be done in an hour, two-hour session?

• 26:12Speaker 01

  That's right.

• 26:13Speaker 00

  Has to be done in a clinic, right?

• 26:15Speaker 01

  Yeah, in the clinic, right. You have to have the right recording apparatus and so on. But that's in principle, as increasing confidence comes in exactly which measurements, one could even imagine moving toward, you know, home tests, but we're not there yet.

• 26:33Speaker 00

  Amazing. I think one of the reasons I get asked about it so much is a lot of people wonder if they have ADHD. Do you think that some of the lifestyle factors that inhabit us all these days could induce a subclinical or a clinical-like ADHD? Meaning if I look at people's phone use, including my own, and I don't think of it like addiction, it looks to me and feels to me more like OCD. And I'll come clean here by saying when I was younger, when I was a kid, I had a grunting tic. I used to hide it. I actually used to hide in the closet because my dad would make me stop. And I used to, I couldn't feel any relief of my mind until I would do this. And actually now, if I get very tired, if I've been pushing long hours, it'll come back.

• 27:15Speaker 01

  Interesting.

• 27:16Speaker 00

  I was not treated for it, but I will confess that I've had the experience of, I always liked sports where it involved a lot of impact. Fortunately, not football, because I went to a high school where the football team was terrible. Maybe that would have avoided more impact. But things like skateboarding, boxing, they bring relief. I feel clarity after a head hit, which I avoid. But I used to say that's the only time I feel truly clear for a long. And then eventually it dissipated. By about age 16, 17, it just disappeared. So I have great empathy for those that feel like there's something contained in them that won't allow them to focus on what they want to focus on.

• 27:55Speaker 00

  And these days, with the phone and all these email, et cetera, I wonder, and I empathize a bit when I hear people saying like, I think I might have ADHD or ADD. Do you think it's possible that our behaviors and our interaction with the sensory world, which is really what phones and email really are, could induce ADD or reactivate it?

• 28:19Speaker 01

  Yeah, this is a great question. I think about it a lot. There's, you know, and you mentioned this, this tic-like behavior in yourself. It's very common that people who have tics have this building up of something that can only be relieved by executing the tic, which can be a motor movement or vocalization or even a thought. And, and people do, I think, these days do have this, if they haven't checked their phone in a while, they do have a buildup, a buildup, a buildup until they can, they can check it and relieve it. And, and, and there's some similarities, you know, there is a little reward that comes with the, with the checking.

• 28:57Speaker 01

  But the key question in all of psychiatry, what we do is we, we don't diagnose something unless it's disrupting what we call social or occupational functioning. Like you could have any number of symptoms, but literally every, every psychiatric diagnosis requires that it has to be disrupting someone's social or occupational functioning. And these days, you know, checking your phone is pretty adaptive. That pretty much helps your social and occupational functioning. And so we can't, we can't make, we can't make it a psychiatric diagnosis.

• 29:29Speaker 00

  Interesting.

• 29:30Speaker 01

  At least in the world of today.

• 29:33Speaker 00

  I'd love your thoughts on psychedelic medicine, putting them into patients and seeing tremendous positive effects, but also tremendous examples of induced psychiatric illness. In other words, many people lost their minds as a consequence of overuse of psychedelics. I'll probably lose a few people out there. But I do want to talk about what is the state of these compounds? And I realize it's a huge category of compounds, but LSD and psilocybin, as I understand, trigger activation of particular serotonin receptor mechanisms may or may not lead to more widespread activation of the brain more that one wouldn't see otherwise. But when you look at the clinical and experimental literature,

• 30:17Speaker 00

  what is your sort of top contour sense of how effective these tools are going to be for treating depression?

• 30:23Speaker 01

  Well, you're, you're right to highlight both the opportunity and, and the peril that is there.

• 30:30Speaker 01

  And of course, we want to help patients and of course, we want to to explore anything that might be be helpful and but we want to do it in a safe and rigorous way. But I I do think we should explore these these avenues. These are agents that alter reality and alter the experience of reality, I should say, in in relatively precise ways. They they do have problems. They can be addictive. They can cause lasting change that is not desirable. Now, that said, even as these medications exist now, as you know, there's an impulse to to use them in very small doses and to use them as adjunctive treatments for for therapy of various kinds.

• 31:15Speaker 01

  And I I'm also supportive of that if done, you know, carefully and rigorously. Of course, there's risk, but there's risk with many other kinds of of treatment. And I'm not sure that the risks for these medications vastly outweigh the risks that we normally tolerate in other branches of medicine.

• 31:32Speaker 00

  Why would they work? I mean, the, you know, let's say that indeed their main effect is to create more more connectivity, at least in the in the moment, between brain areas. So psychedelics seem to be a a trajectory not off too far off from the dream state, where space and time are essentially not as rigid. And there is this element of synesthesia, blending of the senses, you know, feeling colors and hearing light and things of that sort. You hear these reports, anyway.

• 32:13Speaker 00

  Why would having that dreamlike experience somehow relieve depression long term? Do we have any idea why that might be?

• 32:24Speaker 01

  We have some ideas and no no deep understanding. One way I I think about the psychedelics is they

• 32:35Speaker 01

  Increase our willingness to, or they've increased the willingness of our brain to accept unlikely ways of constructing the world, unlikely hypotheses, as it were, as to what's going on. The brain, in particular our cortex, I think, is a hypothesis generation and testing machine. It's coming up with models about everything. It's got a lot of bits of data coming in and it's making models and updating the models and changing them, theories, hypotheses for what's going on. And some of those never reach our conscious mind. And this is something I talk about in projections in the, in the book quite a bit, is many of these are filtered out before they get to our conscious mind. And that's good. We, we think how distracted we'd be if we were constantly having to evaluate all these,

• 33:20Speaker 01

  you know, hypotheses about, you know, what kinds of shapes or objects or processes were out there. And so a lot of this is handled before it gets to consciousness. What the psychedelics seem to do is they change the threshold for us to become aware of these incomplete hypotheses or wrong hypotheses or, or concepts that might be noise but are just wrong and so are never allowed to get into our conscious mind. Now, you know, that, that's pretty interesting and it goes wrong in psychiatric disorders. I think in schizophrenia, sometimes the paranoid delusions that people have are examples of

• 34:01Speaker 01

  these poor models that escape into the conscious mind and become accepted as reality and they never should have gotten out there. Now, how could something like this, in the right way, help with something like depression? Patients with depression often are, are stuck. They, they can't look into the future world of possibilities as effectively. There's, everything seems...

• 34:33Speaker 01

  Hopeless, and what does that really mean? They discount the value of their own action. They discount the value of the world at giving rise to a future that matters. Everything seems to run out, like a river just running out into a desert and drying up. And what these agents may do that increase the flow through circuitry, if you will, the percolation of activity through circuitry may end up doing for depression is increasing the escape of some tendrils of process of forward progression through the world. That's a concept. It's how I think about it. There are ways we can make that rigorous. We can indeed identify in the brain by recording.

• 35:17Speaker 01

  We can see cells that represent steps along a path and look into the future. And we can rigorously define these cells, and we can see if these are altered on psychedelics. And so that's one of the reasons that we're working with these agents in the laboratory to say, is this really the case? Are these opening up new paths or representations of paths into the future?

• 35:43Andrew D. Huberman?

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• 37:29Speaker 00

  MDMA, ecstasy, is a unique compound in that it leads to big increases in brain levels of dopamine and serotonin simultaneously. And I realize that the neuromodulators like dopamine and serotonin often work in concert, not alone, the way they're commonly described in the, you know, the more general popular discussions. However, it is a unique compound, and it's different than these serotonergic compounds like LSD and psilocybin. And there are now data still emerging that it might be, and in some cases, can be useful for

• 38:09Speaker 00

  the treatment of trauma, PTSD, and similar things. Why, why would that work? And do you, and a larger question, perhaps the more important question is psychedelics, MDMA, LSD, all those compounds, they're, in my mind, there are two components. There's the experience you have while you're on them, and then there's the effect they have after. People are generating variations of these compounds that are non-hallucinatory variations. But how crucial do you think it is to have, let's stay with MDMA, the experience of

• 38:46Speaker 00

  Huge levels of dopamine, huge levels of serotonin, atypical levels of dopamine and serotonin released, having this highly abnormal experience in order to be normal again.

• 38:55Speaker 01

  Yeah. I think the brain learns from those experiences. That's, that's the way I see it. And, and so, for example, people on, who've taken MDMA, they will, as you say, they'll have, they'll be the acute phase of being, you know, on the, the drug and experiencing this extreme connectedness with other people, for example. And then the, the drug wears off and, but the brain learned from that experience. And so what, what people will report is, yeah, I'm not, I'm not in that state, but I saw what was possible. You know, I saw, yeah, you can, there don't need to be barriers, or at least not as many barriers as, as I thought. I can

• 39:36Speaker 01

  connect with more people in a, in a way that, that is helpful. And so I think it, it's the learning that happens in that state that actually matters.

• 39:45Speaker 00

  And this, as you described, that, that sounds a lot like what I understand to be the hallmark feature of really good psychoanalysis, that the relationship between patient and therapist, hopefully evolves to the point where these kinds of tests can be run within the context of that relationship and then exported to other relationships. Is that?

• 40:04Speaker 01

  Exactly right, yeah.

• 40:05Speaker 00

  And, and that probably, I'm assuming, is still the goal of really good psychiatry also?

• 40:10Speaker 01

  It's a part of,

• 40:11Speaker 00

  Intimacy, really.

• 40:12Speaker 01

  It, it should be, when we have time, I think all, all good psychiatrists try to achieve that, that level of, of, of connection and learning. Try to help patients create a new, a new model that is stable, that is learned, and that can, you know, help instruct future behavior.

• 40:32Speaker 00

  One of the things that I took from reading your book, in addition to learning so much science and the future of psychiatry and brain science was,

• 40:43Speaker 00

  You know, amidst these very, it makes it very tragic cases and sadness and a lot of the, the, uh, the weight that that puts on the clinician, on you also, that there's a, that there's a central chord of optimism, that where we're headed is not just possible, but very likely and, and better.

• 41:04Speaker 01

  Yeah.

• 41:05Speaker 00

  And, um, you know, are you an optimist?

• 41:09Speaker 01

  I am. And this, this is, by the way, this was a really interesting experience in writing projections because I had a, a dual goal. I wanted it to be for everybody, literally everybody in the world who wants to, to, to, to read it. And yet, at the same time, I wanted to, uh, stay absolutely rigorously close to the, the science, what was actually known. Um, when I was speaking about science, when I was speaking about the, the neurobiology of the, of the brain or psychiatry, I wanted to, to not have any of my scientific colleagues think, oh, he's, he's going too far, he's saying too much. And so I had these, these

• 41:50Speaker 01

  two goals, which I kept in my mind the entire time. And a lot of this, trying to find exactly the right word, we talked about was on this path of staying excruciatingly rigorous in the science and yet, letting people see the hope, the, the, where things were, have everybody see that we've come a long way, we have a long way to go. But, but the trajectory and the, the path is, is beautiful. And so that, that, that was the, the goal, I, I think, uh, you know, of course, that sounds almost impossible to, to jointly satisfy those two, those two goals, but I kept that in my mind the whole way through. And yes, I am optimistic and I hope that came through in the book.

• 42:32Speaker 00

  But it certainly did. And at least from this colleague, um, uh, you, you did achieve both. And, um, it's a wonderful, it's, it's a masterful book, really, and one that, as a scientist and, um, somebody who is a, a fellow brain explorer, uh, hits all the marks of, of rigor and is incredibly interesting. And there's a ton of storytelling. Definitely, uh, check out the book. Um, there are other people in our community that of course are going to, uh, uh, be reaching out on your behalf, but it's, it's incredible that you juggle this enormous number of things.

• 43:08Speaker 00

  Perhaps even more important, however, is that it's all in service to this larger thing of relieving suffering. So, thank you so much for your time today, for the book, and the work that went into the book, I can't even imagine, for the laboratory work in the development of channel ops and clarity and all the related technologies, and for the clinical work you're doing, and for sharing with us.

• 43:28Speaker 01

  Well, thank you for all you're doing and reaching out. I'm very impressed by it. It's important, and it's so valuable. And thank you for taking the time and for all your gracious words about the book. Thank you.

• 43:45Speaker 03

  Mr. President, my company told me of the explosion on our rig.

• 43:48Speaker 04

  On October 2nd.

• 43:49Speaker 03

  Causing massive water displacement and triggering a tsunami. They all heap the blame on me.

• 43:54Speaker 04

  Tom Cruise is. Digger got us into this mess. And Digger's gonna dig us up. From the director of Birdman and The Revenant.

• 44:02Speaker 05

  What would happen if I stopped drilling? You stop, you freeze to death, that's what.

• 44:06Speaker 04

  With great power comes great deniability.

• 44:09Speaker 05

  I'm not the first then.

• 44:10Speaker 04

  Digger. See the trailer online. Only in theaters October 2nd. Rated R. Under 17 not a minute without parent.