Huberman Lab - Essentials: Psychedelics for Treating Mental Disorders | Dr. Matthew Johnson

Episode Date: July 24, 2025

In this Huberman Lab Essentials episode, my guest is Dr. Matthew Johnson, PhD, a senior researcher for the Center of Excellence for Psilocybin Research and Treatment at Sheppard Pratt’s Institute fo...r Advanced Diagnostics and Therapeutics. We explore the science and therapeutic potential of psychedelic medicine, including psilocybin, MDMA and LSD. We discuss how these substances can profoundly alter perception and self-identity, providing long-lasting relief from depression, addiction and trauma when used in controlled clinical settings. We also discuss microdosing and emerging research on psychedelics’ potential to support recovery from neurological injuries. Read the episode show notes at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman David: https://davidprotein.com/huberman BetterHelp: https://betterhelp.com/huberman Timestamps 00:00:00 Matthew Johnson; Psychedelics 00:01:44 Different Classes of Psychedelics 00:04:33 Psychedelics & Altering Models 00:06:18 Sponsor: David 00:07:33 LSD, Psylocibin & Serotonin 00:09:55 Psychedelic Clinical Trials 00:13:40 Therapy, Trust, Psychedelics 00:16:47 Letting Go & Psychedelic Experience, Self-Representation, Lasting Changes 00:22:31 Sponsors: AG1 & BetterHelp 00:25:26 MDMA, Dopamine & Serotonin; Bad Trips & Transcendental Experience 00:28:49 Dangers of Psychedelics 00:31:11 Microdosing Psychedelics, Antidepressant 00:35:27 Head Injuries, Psychedelics, Depression 00:38:29 Acknowledgements Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

Transcript
Discussion (0)
Starting point is 00:00:00 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. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now my conversation with Dr. Matthew Johnson. Well, Matthew, I've been looking forward to this
Starting point is 00:00:22 for a long time. I'm a huge fan of your scientific work, and I'm eager to learn from you. Likewise. Big fan and happy to do this with you. Well, thank you. My first question is a very basic one, which is what qualifies a substance as a psychedelic? Nomenclature is a real challenge in this area of psychedelics. So starting with the word psychedelic, it just, if you're a pharmacologist, it's not very satisfying because that term really spans different pharmacological classes.
Starting point is 00:00:57 In other words, if you're really concerned about receptor effects and the basic effects of a compound, it spans several classes of compounds. But overall, so it's really more of a cultural term or it does have a relationship to drug effects, but it's at a very high level. So all of the so-called psychedelics across these distinct classes that I can talk more about. The way I put it is they all had the ability to profoundly alter one's sense of reality and that can mean many things. Part of that is profoundly altering the sense of self acutely. So when someone's on the psychedelic. So the different classes that can be the specific pharmacological classes that can be called
Starting point is 00:01:50 a psychedelic are one that what are called the classic psychedelics. So in the literature, you'll see that term and hallucinogen and psychedelic are all have traditionally been used synonymously. I think there was a little bit tendency to stay away from psychedelics of the baggage, but there's been a return to that in the last several years. But the classic psychedelics or classic hallucinogens are things like LSD, psilocybin, which is in so-called magic mushrooms. It's in over 200 species that we know of so far of mushrooms.
Starting point is 00:02:25 Dimethyltryptamine or DMT, which is in dozens and dozens of plants. Mescaline, which is in the peyote cacti and some other cacti like San Pedro. And even amongst these classic psychedelics, there are two structural classes. So that's the chemistry. There are two structural classes. So that's the chemistry. There's the tryptamine-based compounds like psilocybin and DMT, and then there's the phenethylamine-based compounds.
Starting point is 00:02:53 So these are the two basically building blocks that you're starting from, either a tryptamine structure or a phenethylamine structure. But that's just the chemistry. What's more important, or at least to someone like me, are the receptor effects,
Starting point is 00:03:10 and then ultimately that's going to have a relationship to the behavioral and subjective effects. So all of these classic psychedelics serve as agonists or partial agonists at the serotonin 2A receptor, so subtype of serotonin receptor. Then you have these other classes of compounds that you could call psychedelic.
Starting point is 00:03:30 Another big one would be the NMDA antagonist. So this would include ketamine, PCP, and dexamethorphin, something I've done some research with which folks might recognize from like robo-tripping, guzzling, like, you know, call syrup. A large overlap in the types of subjective effects that you get from those compounds
Starting point is 00:03:49 compared to the 2A agonist classic psychedelics. But then you have another big one, MDMA, which really stands in a class by itself. So it's been called an intactogen and... What does that mean? It means like touching within. It sort of elutes the idea that it can really put someone in touch with their emotions.
Starting point is 00:04:11 It's also been called an empathogen, meaning can afford empathy. So I get the impression that the psychedelic space is a enormous cloud of partially overlapping compounds. Right. Meaning some are impacting the serotonin system more than the dopamine system. Others are impacting the dopamine system
Starting point is 00:04:30 more than the serotonin system. Given that the definition of a psychedelic is that it profoundly alters sense of self, at least that's included as a partial definition. I think of these as psychedelics as profoundly altering models. You know, we're all, you know, we're prediction machines and that's large, so much of that is top down and psychedelics have a good way of, you know, loosely speaking, dissolving those models. And one of the realities- Can you give us an example of one of, you know, loosely speaking, dissolving those models.
Starting point is 00:05:05 And one of the realities... Can you give us an example of one of like a model? Like I know that when I throw a ball in the air, it falls down, not up. This might sound extreme, but there are these cases. It was over overblown in sort of the propaganda, the late 60s, early 70s. But there are credible cases of people. I think it's very atypical, of sounds like they really thought they could fly and jump out of a window.
Starting point is 00:05:32 Now, far more people every year fall, I mean, who knows, they fall and die out of, from height because they're drunk. So it's extremely rare. But, you know, there are some like pretty convincing cases. There was one research volunteer in our studies that she looked like she was in one of our studies, like she was trying to dive through a painting on the wall. She was fine, but she reviewing the video, it looked like she really thought that she was going to go through that painting and who knows the other dimension.
Starting point is 00:06:15 Yeah. So they're violating these predictions. I'd like to take a quick break and acknowledge one of our sponsors, David. David makes a protein bar unlike any other. It has 28 grams of protein, only 150 calories and zero grams of sugar. That's right, 28 grams of protein and 75% of its calories come from protein. This is 50% higher than the next closest protein bar. David protein bars also taste amazing.
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Starting point is 00:07:28 Again, that's davidprotein.com slash Huberman. Given the enormous cloud of different substances and given the range of previous experiences that people show up to a psychedelic experience with, I feel like the ability to extract some universal themes is useful, especially for people who haven't done them before, right? Who might not have an understanding of what their effects are like. Can we just briefly touch on the serotonin system?
Starting point is 00:07:58 So compounds like LSD, lysergic acid, diethylamide, and psilocybin. My understanding is that they primarily target the serotonin system. How do they do that at a kind of general level? And why would increasing the activity of a particular serotonin receptor or batch of serotonin receptors lead to these profoundly different experiences that we're
Starting point is 00:08:25 calling model challenges, challenging pre-existing models and predictions. I mean, at the end of the day, it's a chemical and these receptors are scattered around the brain with billions of other receptors. What do we think is going on in a general sense? Yeah, yeah. And this is really the area of active exploration and we don't have great answers. We know a good amount about the receptor level pharmacology,
Starting point is 00:08:53 some things about post receptor signaling pathways. In other words, just fitting into the receptor, clearly, you know, serotonin itself is not psychedelic, you know, or else we'd be tripping all of us all the time. Because when I eat a bagel, I get serotonin release, right? Uh-huh. I mean, there's a... And it's very different than LSD.
Starting point is 00:09:10 I mean, there's tryptophan, right? My understanding of serotonin is that in very broad strokes, that it generally leads to a state of being fairly... It pushes the mind and body towards a state of contentment within the immediate experience. Whereas the dopamine system really places us into an external view of what's out there in the world and what's possible. Yeah.
Starting point is 00:09:33 Is that fair to say? Need to do something. I mean, that's consistent with my understanding. And I'll certainly not in terms of, I don't primarily identify as a neuroscientist. Definitely tell the viewers that we're far more in your domain here than mine, but in terms of how psychedelics and other drugs, interface at the neuroscience level. Well, feel free to explain it at the experiential level.
Starting point is 00:09:58 Yeah. I mean, it doesn't have, let's say I were to come to one of your clinical trials, because these are clinical trials, right? And in your, at your lab at Hopkins. Yeah. And would I need to be depressed or could I just be somebody who wanted to explore psychedelics?
Starting point is 00:10:10 We've had studies for all of these and a number of other disorders. So healthy normal studies, the code for not a problem to fix, but we're all here. That's what's amazing about psychedelics though, because if you administer them under this model and you develop a relationship and give a high dose of psychedelic,
Starting point is 00:10:27 you can be healthy normal without a diagnosable issue. But man, we're all human and the issues seem to come to the surface. So, but we've done work with smoking cessation. So people trying to quit tobacco and haven't been successful. So a variety of reasons. So maybe I'll just ask some very simple questions
Starting point is 00:10:44 that would kind of step us through the process. So let's say I were to sign up for one of these trials and I qualified for one of these trials. I'd show up. You said I would do several hours in advance of getting to know the team that would be present during this psychedelic journey. First there's screening. So it's kind of like a couple of days of both psychiatric, like structured psychiatric interviews about your whole, your past and symptoms across the DSM, the psychiatric Bible to see if you might have various disorders that could disqualify you. Like the main ones being the psychotic disorders,
Starting point is 00:11:18 schizophrenia, and also including bipolar. So the manic side of bipolar. So after that's in also cardiovascular screening, heart disease, after that screening, including bipolar, so the manic side of bipolar. So after that's in also cardiovascular screening, heart disease, after that screening, then the preparation where you get, you're both, you develop a therapeutic rapport with the people who are gonna be in the room with you,
Starting point is 00:11:36 your guides, but you're also then didactically sort of explained about what the psychedelic could be like. And that's kind of a laundry list because they're more known by their variability You could have the most beautiful experience of your life or the most terrifying experience of your life So it's this kind of laundry list of like the things that could happen. So there's no surprises I think it's so important for people to hear because you really can't predict how somebody is going to react internally let's say that somebody passes all the prerequisites and it's the day.
Starting point is 00:12:11 Comes the day that they're going to have this experience. Are they eating mushrooms like you hear about or are they taking it in capsule form? And how do they get it into their body? So they receive pure psilocybin. Most of our studies are looking at where we want a psychedelic effect taking it in capsule form and how do they get it into their body? So they receive pure psilocybin. Most of our studies are looking at where we want a psychedelic effect are in the 20 to 30 milligram range.
Starting point is 00:12:33 The session day itself is not full of, for most of our studies is not full of tasks. We really want to look at the therapeutic response. Obviously, if it's a therapeutic study, we want it to be a meaningful experience. And research has found, not surprisingly, that you get a less meaningful experience when you're in an fMRI or when you're doing a lot of cognitive tasks. So our typical therapeutic model, which, again, isn't just limited necessarily to the therapeutic studies where we're trying to treat a specific disorder, is to have that preparation so the person feels very comfortable with their guides. Ultimately, what I tell people is like any emotional response, it's all welcome.
Starting point is 00:13:15 I mean, you could be crying like a baby hysterically. That's what you should be doing if that's what you feel like. I mean, you're doing therapy for people. It's not just about the experience. Right. And the experience itself is very much shaped by that container, by the environment. And the degree to which one allows it to happen. One should let go of control.
Starting point is 00:13:39 The letting go of control is an interesting feature, actually, because one of the common themes of good psychoanalysis or psychotherapy of any kind is that there's a trust built between the patient and the analyst, and that relationship becomes a template for trust more generally and trust in oneself. How do you convince people to go further and further down that path?
Starting point is 00:14:02 What do you think allows them to do that? Because I think that to me is one of the more unusual aspects to psychedelics is that normally the social pressure, but also just our internal pressure from our own brain is pay attention to many things at once, not just one. Is that- Especially these days.
Starting point is 00:14:22 Yeah, multi-task. Multi-task and the more that we focus on one thing, the more bizarre that thing actually can appear to us, right? Right. I mean, even if it's the tip of your finger and you're not taking any psychedelics, you spend a long enough looking at the tip of your finger, you will notice some very weird things. Yeah.
Starting point is 00:14:38 Right? I think of that as the classic psychedelic effect or one classic effect, and one I've used many times of this example of why people shouldn't necessarily, you know, these aren't, one should be judicious in putting themselves in these circumstances. Someone could be, you know, having a very strong psilocybin experience and they're trying to navigate their way in Manhattan,
Starting point is 00:15:04 crossing the street, and they might be staring into the hand and realize, like that's, their hand is the most amazing miracle. Like the entire universe has essentially conspired to come to this one point to make this absolutely breathtaking. It's almost like, I think of the simplest form of, of, of, well, we know the simplest form of learning is habituation. Simply keep applying stimuli and there's less response. Like this is what organisms do. This is what we have to do. And it's like, there's this dishabituation component
Starting point is 00:15:31 that like- Dishabituation. Yes, like we wouldn't be able to get through life if we wouldn't be able to cross that street if we were like, this is a miracle. It sounds like on psychedelics, one of the primary goals therapeutically is to really drill into one of these perceptual bubbles
Starting point is 00:15:47 and expand that bubble. And the safety it seems is the safety, it's sort of like a permission to do that without worrying that something's gonna happen. Right, because I've had people there on the couch. Yeah, I remember one lady said, this is probably 13, 14 years ago, said, Matt, tell me again, I can't die. Like, I feel like my heart is going to rip through my chest.
Starting point is 00:16:12 I mean, she was feeling her. And I should say, typically cardiovascular response is modest, the pulse and blood pressure go up. And if it goes over a certain level, we have a protocol and we've had to do this only a few times, but the physician comes in, gives them a little nitroglycerin under the tongue, and knocks the blood pressure down a little bit, doesn't affect the experience. So we have it all in place, even though they'd probably be found out of an abundance of caution. But yeah, but someone can feel that, my God, I'm going to die. Like I have never felt my heart beat like this before. So there's an expansion of a particular fairly narrow percept.
Starting point is 00:16:52 It could be sound, could be an emotion, could be sadness, could be a historical event or a fear of the future. And you've mentioned before that there's something to be learned in that experience. There's something about going into that experience in an undeterred way that allows somebody to bring something back into more standard reality. Given the huge variety of experiences that people have on psychedelics, given the huge variety of humans that are out there, but what are now very clear therapeutic effects in the realm
Starting point is 00:17:31 of depression, what do you think is the value of going into this fairly restricted perceptual bubble, what we are calling letting go or giving up control. Because if the experiences are many, but the value of what one exports from that experience is kind of similar across individuals, that raises all sorts of interesting questions. And this is not a philosophy discussion. We're talking about biology and psychology here. What are your thoughts on that? This is in the terrain we're figuring out, you know, so there's no, the educated speculation is the best I can provide.
Starting point is 00:18:08 But I, I think the best, the, the, the, the most, I think the common denominator are persisting changes in self representation. Okay. Tell me more about self-representation. That's the way one holds the sense of self, the fundamental relationship of a person in the world. I mentioned earlier that these experiences seem to alter the models we hold of reality. And I think that the self is the biggest model, that I am a thing that's separate from other things and that I am defined by certain, I have a certain
Starting point is 00:18:46 personality and I'm a smoker that's having a hard time quitting or I'm a depressed person that, you know, views myself as a failure and all of these things, those are models too. So this is this expansion of the perceptual bubble, a narrow, a narrow percept that then grows within the confines of that narrow percept. So sense of self is a very interesting phenomenon. If we could dissect it a little bit, there's the somatic sense of self, so the ability to literally feel the self in this process we call interoception. And then there's the title of the self, the I am blank. And I noticed you said that several times.
Starting point is 00:19:25 It's intriguing to me how one defines themselves internally, not just to other people, but how one psychologically and by default defines themselves, I think is a very powerful, like, and depressed people, as well as happy people seem to define themselves in terms of these categories of emotional states. So I think it's so interesting that letting go
Starting point is 00:19:51 and going into this perceptual bubble, which is facilitated by obviously a really wonderful team of therapists, but also the serotonergic agent, allows us to potentially reshape the perception of self. That's a tremendous feat of neuroplasticity. Right, I think there's something about this change in sense of self.
Starting point is 00:20:13 There seems to be something on the identity level, both with, I think, the work we did with cancer patients who had substantial depression and anxiety because of their cancer, and also our work with people trying to quit cigarette smoking. I mean, there's this real, there seems to be when it really works,
Starting point is 00:20:29 this change in how people view themselves, like with smoking, like really stepping out of this model, like I'm a smoker, it's tough to quit smoking cigarettes. I can't do it, I failed a bunch of times. I remember one participant during the session, but he held onto this afterwards said, my God, it's like, I can really just decide. Like flicking off a bike, I can decide not to smoke.
Starting point is 00:20:56 And it's, I call these duh experiences with psychedelics because people often, like in the cancer state, you say, I'm causing most of my own suffering. Like I can follow my appointments, I can do everything, but I can still plan for the vacation. I'm not getting outside in the sunshine. I'm not playing with my grandkids. I'm choosing to do that.
Starting point is 00:21:14 And it's like, they told themselves that before and the smoker has told themselves a million times. I can, so it sounds, when it comes out of their mouths, folks will say, this is part of the ineffability of a psychedelic experience, folks say, I know this sounds like bullshit and this sounds like, but my God, I could just sigh. Like they're feeling this gravity of agency that seems to be at times fundamentally like supercharged
Starting point is 00:21:40 from a psychedelic experience. This idea like, I'm just gonna make a decision. Like normally, like you tell a depressed person, like don't think of yourself that way. You're not a failure. Look at all the, it's just, yeah. It's like, and you can actually, in one of these states, have an experience where you realize like, my God,
Starting point is 00:21:57 just like using MDMA to treat PTSD, and we're gonna be starting work with psilocybin to treat PTSD. Someone could really reprocess their trauma in a way that has lasting effects. And clearly there's probably something, you know, reconsolidation of those memories. They are altered, you know, very consistent with our understanding of the way memory works. So the whole idea, people can actually in a few hours have such a profound experience that they decide
Starting point is 00:22:27 to make these changes and who they are and it sticks. I'd like to take a quick break and acknowledge our sponsor, AG1. AG1 is a vitamin mineral probiotic drink that also includes prebiotics and adaptogens. As somebody who's been involved in research science for almost three decades and in health and fitness for equally as long,
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Starting point is 00:25:22 Again, that's betterhelp.com slash Huberman to get 10% off your first month. Again, that's betterhelp.com slash Huberman. I'm fascinated by this idea that a somatic and a perceptual experience, but a real experience of the sort that you're describing, is what allows us to reshape our neural circuitry and to feel differently about ourselves. And I know there's been really tremendous success in many individuals of alleviating depression,
Starting point is 00:25:48 treating trauma with these different compounds. If we could, I'd like to just ask about some of the more dopaminergic compounds, in particular MDMA. And my understanding is that MDMA leads to very robust increases in both dopamine and serotonin simultaneously. So why would it be that having this increased dopamine and increased serotonin would provide an experience that is beneficial? And how do you, to the extent that you can describe it, how do you think that experience
Starting point is 00:26:23 differs from the sorts of experiences that people have on psilocybin or more serotonergic agents? Speculating, but it may be that MDMA for a broader number of people is better for trauma because the chances of having an extremely challenging experience, what I call the bad trip, like really freaking out is much lower with MDMA. People can have bad trips, but they're of a different nature. It's not sort of like freaking out because all of reality is sort of shattering and it's less of this, it can take so many forms with the classic psychedelics,
Starting point is 00:27:02 but like typically you'll hear something like, I didn't know it was gonna be like this, no matter how hard you tried to prepare them, that like, this is, like, get me off this ride. You're talking about LSD or psilocybin. LSD, psilocybin, IY. That's true. Yeah, yeah, and just this sense of like,
Starting point is 00:27:21 I'm going insane, this is so far beyond anything I've ever experienced. And it's scaring the shit out of me. I don't have a toe hold on anything. Even that I exist as an entity. And that can be really, I think frankly, experientially, that's kind of the gateway to both the transcendental mystical experiences, the sense of unity with all things, which we know our data suggests is related to long-term positive outcomes. Wait, I want to make sure I understand.
Starting point is 00:27:54 So you're saying the bad trip can be related to the transcendental experience? Right, I think those are both speculating, but you have to pass through this sort of like, reality shattering, including your sense of self. And one can handle that in one of two ways. You can either completely surrender to it or you can try to hang on.
Starting point is 00:28:15 And if you try to hang on, it's going to be more like a bad trip. So again, I wish there was more and hopefully there will be more experimentation. There's a lot going on here in the black box in terms of the operant behavior of how you are, you know, within yourself choosing to handle, like letting go, you know, and eventually we'll be able to see this in real time with brain imaging, ah, there they are surrendering to the psychedelic experience.
Starting point is 00:28:39 Here they are trying to hold on, but we're not there yet. But I think it's a good through clinical observation seems pretty clear that something like that is going on. There has been an attempt at creating this movement toward openness about psychedelics and their positive effects. This has happened before. The difference is that now there are people like you inside the walls of the university or publishing peer-reviewed studies and things of that sort. The question is to me, you know, what are the valuable exports, right? And where does the extreme lie? I mean, clearly there's a problem with
Starting point is 00:29:18 tinkering with reality through pharmacology. And there's a benefit, it sounds like, to tinkering with reality through pharmacology. And for the average person, right, or for kids that are hearing this, kids that are in their teens, right? Yeah. What are the, I want to talk about, what are the dangers of psychedelics? This is something you don't hear a lot about these days,
Starting point is 00:29:39 and it's not because I'm anti-psychedelic at all, but what are the dangers? Yeah, so these can be profoundly destabilizing experiences and ones that, you know, ideally are had in a safe container, you know, sort of where someone, you know, what are the relevant dangers and what can we do to mitigate those. So there's two biggies. One, and I've already mentioned, it's people with very severe psychiatric illness, not depression, not anxiety. I'm talking about psychotic disorders like schizophrenia or mania as part of bipolar
Starting point is 00:30:24 disorder. The far more likely danger is the bad trip. Anyone can have this. The most psychologically healthy person in the world probably. You jack the dose high enough and especially in a less than an ideal environment, you can have a bad trip. You even get it in an ideal environment like ours at a high dose of around 30 milligrams of psilocybin. After the best preparation we can provide, about a third of people will say essentially
Starting point is 00:30:51 at some point they have a bad trip. At some point within the entire journey. Right. Now they could have one of the most beautiful experiences of their life sometimes, like a couple minutes later, but at some point they had a sense of strong anxiety, fear, losing their mind, feeling trapped, something like that. I definitely want to ask you about microdose
Starting point is 00:31:13 versus standard or macrodosing psilocybin. I'm micro-cynical, if you will, about this term microdose. Is there any clinical evidence or peer-reviewed published evidence that it works quote unquote to make people feel better about anything? So yeah, the claims are, and there are a number of them, there's two general ones. One is sort of acting in place of the ADHD treating drugs, so the psychomotor stimulants, so like a better version of Adderall. The other claims are essentially
Starting point is 00:31:45 a better version of the traditional antidepressants, a better version of Prozac. None of the peer-reviewed studies that have much credibility, none of them have shown a benefit. The handful of studies that have done that have shown they've ranged from finding no effect whatsoever to just a little bit of impairment, like impairing someone's ability to do time estimation and production tasks. So you want an accurate sense of time, at least if you're navigating in the real world.
Starting point is 00:32:17 It's different if you're on the couch on a heroic dose for therapeutic reasons where you're safe, but if you're crossing the street, if you're getting, you know, in your work life, which is the way people are claiming to use that, it helps them be a better CEO. Like you want an accurate sense of time. So if anything, the data suggests that it makes it a little bit less accurate.
Starting point is 00:32:37 And there's evidence that someone feels a little bit impaired and they feel a little bit high. So in terms of, you know, you call that abuse liability in research. So far, no studies have shown, you know, any increase in creativity, enhancement of any form of cognition, or a sustained improvement in mood.
Starting point is 00:33:02 Now, no studies have actually looked at the system of microdosing that the aficionados are claiming. Folks like Paul Stamets and others, they'll have particular formulas. They're like, you need to take it one day and then take so many days off and take it every four days. And they really say you need to be on it for a while. Like a few weeks in, you may start to notice through this pattern of using it, and you're feeling the benefits on those off days, like the three or two days in between your active doses. So those are the claims. Again, we don't know that there's any truth to that working, but studies have not been
Starting point is 00:33:40 done to model that. So that's a big caveat. My bet is, and this is totally based on anecdotes, that I think there is probably a reality to the anti-depressant effects. I find that more intriguing because of the suffering with depression. Even if it's, it wouldn't be as interesting as I think what we're doing with high dose psilocybin
Starting point is 00:34:02 or psychedelics to treat depression. It would be, if this is developed and there's a reality, it would be more like a better, you know, perhaps a better SSRI, a better Prozac. Which are similar. That being said, we need more tools than fewer tools in the toolbox. And it shouldn't be that surprise. Like even before the, going back to the tricyclics and the MAO inhibitors, going back to the 50s,
Starting point is 00:34:25 like augmenting extracellular serotonin in one way or another for many people leads to a reduction in depressive symptoms. It wouldn't be that crazy for chronically stimulating a subtype of serotonin receptor that you have an antidepressant effect. So I think if I had put my bets on it, that if there's anything real, it is in that category.
Starting point is 00:34:47 Although I'm very open to like, maybe there is something to the creativity, to the improved cognition, which covers many domains in and of itself. But my greatest hopes are on the antidepressant effects. That said, in the big picture, I think all of the most interesting thing about psychedelics are the heroic doses. I mean, the idea that you can give something one, two, three times and you see improvements
Starting point is 00:35:13 in depression months later and in addiction over a year later and with these people dealing with potentially terminal illness. I mean, I'm interested in big effects. I wanna make sure that I ask you about the other really important mission that you're involved in with respect to psychedelics, which is not about depression per se, but is about neurological,
Starting point is 00:35:37 a neurologic injury or head injury. We always think sports, but there are many people who make a living in a way that is over time is detrimental to their brain. What do you think is the potential for these compounds, particular psilocybin, but other compounds as well for the treatment and possible even reversal of neurological injuries? There are anecdotes of people saying that psychedelics have helped heal their brain.
Starting point is 00:36:08 You know, they've been in one of these situations, like in sports, a sport where there's repetitive head impact, and they're claiming that using psychedelics has actually improved their cognitive function, for example, improve their memory. If you take these anecdotes and you combine it way across orders of analysis to the rodent research from several labs like David Olson, Brian Roth, these folks that have shown different forms of neuroplasticity unfolding, those effects may be at play and they improve in the psychiatric treatments that we're dealing with. We don't know that. It seems like a decent guess and we're going maybe at play in the psychiatric treatments that we're dealing with, we don't know that. It seems like a decent guess,
Starting point is 00:36:49 and we're gonna be figuring out whether that's the case. But another potential that that sets up is that maybe that's what's going on with these claims of improvements from neurological issues that there's actually, you know, a repair of the brain from injuries underlying, you know, things that, you know, situations where there's repetitive head impact,
Starting point is 00:37:17 perhaps there's a potential for helping folks recover from stroke and disorders like that. It is more exploratory, But what I'm hoping to do is some work with retired athletes who have been exposed by the nature of their sport, for example, in NA athletes in the UFC, who have been exposed to repetitive head impacts like a lot of sports, a lot of, you know, sports exposed people to, and who are retired from the sport and are suffering from say depression, which can in part result from those types of,
Starting point is 00:37:53 of that history of head impact. See if we can fix the depression, but then also as a cherry on top and a more exploratory aim, see if we can have evidence of improvement in cognitive function and associate like using MRI, see if it affects gray matter over time, these types of things to see if there are actually
Starting point is 00:38:15 some evidence of this improved, like this more direct repair of the brain. But again, it is very sort of like, we've got some rodent data, we've got some human anecdotes. We will acknowledge it's early days and we look forward to seeing the data. I appreciate how cautious you are,
Starting point is 00:38:36 and tentative you are. You're not drawing any conclusions. Thank you so much for your time, for your knowledge. And I think you put it best earlier for holding the candle in a very dark time. And then now, for your knowledge. And I think you put it best earlier for holding the candle in a very dark time. And then now there's light.

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