The Science of Psychedelics for Mental Health | Dr. Robin Carhart-Harris

1. 0:00 – 2:12

   Dr. Robin Carhart-Harris

   1. AHAndrew Huberman0:00

      (music plays) 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. Today, my guest is Dr. Robin Carhart-Harris. Dr. Carhart-Harris is a distinguished professor of neurology and psychiatry at the University of California San Francisco. He is one of the leading researchers in the field of psychedelics and how they change neural circuitry in the brain. His laboratory is responsible for understanding, for instance, how psilocybin, also sometimes referred to as magic mushrooms, change neural circuitry in the brain such that new ideas and new forms of learning occur. His laboratory is also responsible for carrying out various clinical trials, some of which have demonstrated that appropriate dosages of psilocybin can alleviate major depression in more than 67% of people that take the drug. Now, this is not to say that everybody should take psilocybin, and today's discussion describes both the clinical trials and why treatments with psychedelics in some cases work and in some cases do not work in order to treat major depression, as well as discussions around psilocybin, lysergic acid diethylamide, sometimes also referred to as LSD, as well as DMT, and how these change the brain, and how those brain changes can relate to changes in mental health as it relates to depression and other psychiatric challenges, as well as how psychedelics are being applied in order to change neural circuitry for sake of expanding different aspects of the human mind, including creativity, intelligence, and much more. During today's discussion, Dr. Carhart-Harris teaches us about the history of the study of psychedelics, as well as how the legislature, that is the laws surrounding psychedelics, are evolving in the United States and elsewhere for the use of psychedelics to treat psychiatric challenges. By the end of today's discussion, you will have a thorough understanding of how psychedelics work, both in the short term during the actual journey or trip. In fact, much of my discussion today with Dr. Carhart-Harris talks about the different aspects of the psychedelic journey and how those relate to therapeutic outcomes. And of course, by the end of today's discussion, you will also understand the long-term effects of psychedelics, that is how they can actually rewire

2. 2:12 – 5:41

   Sponsors: Eight Sleep, Levels, HVMN

   1. AHAndrew Huberman2:12

      the brain. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. I've talked many times before on this podcast about the fact that sleep is the foundation of mental health, physical health, and performance. One absolutely critical variable to getting excellent sleep is the temperature of your sleeping environment. That is, in order to fall and stay deeply asleep at night, your body temperature needs to actually drop by about one to three degrees, and in order to wake up in the morning feeling refreshed and alert, your body temperature has to increase by about one to three degrees. There are a lot of ways to control the temperature of your sleeping environment, but one of the best ways is to control the temperature of your actual mattress, the surface that you're sleeping on. With Eight Sleep, you can do this very easily. There's a simple-to-use app where you can program in the temperature of your mattress across the night. So you can make it slightly cool at the beginning of the night, getting cooler, putting you into deep sleep and then rapid eye movement sleep, and all of that, in terms of its impact on your sleep, can be tracked within the same app. I've been sleeping on an Eight Sleep mattress cover for more than two years now, and it has completely transformed my sleep. If you'd like to try Eight Sleep, you can go to EightSleep.com/huberman for their exclusive Memorial Day savings now through June 5th, 2023. Eight Sleep currently ships in the USA, Canada, United Kingdom, select countries in the EU and Australia. Again, that's EightSleep.com/huberman. Today's episode is also brought to us by Levels. Levels is a program that lets you see how different foods affect your health by giving you real-time feedback on your diet using a continuous glucose monitor. One of the most important factors in terms of your energy levels and your immediate and long-term health are your blood glucose or blood sugar levels, as they're commonly called. With Levels, you can assess how different foods and activities impact your blood glucose levels. When I did this, it taught me several things. First of all, it taught me that certain foods really spike my blood glucose levels, and while spikes in blood glucose aren't always a bad thing, I was able to assess how certain foods were spiking my blood glucose too much, such that I would have post-eating dips in energy levels, and by removing those foods and substituting in other foods, really evened out my energy levels. So if you're interested in learning more about Levels and trying a continuous glucose monitor yourself, go to Levels.Link/huberman. Right now, Levels is offering an additional two free months of membership. Again, that's Levels.Link/huberman. Today's episode is also brought to us by HVMN Ketone IQ. Ketone IQ is a ketone supplement that increases blood ketones. Now, most people have heard of the so-called ketogenic diet, but most people, including myself, are not on the ketogenic diet. That is, I, and most people, eat complex carbohydrates, fruits and things of that sort, in addition to quality proteins, et cetera. It turns out that even if you're not following a ketogenic diet, increasing your blood ketones can still have benefits. So for instance, I use Ketone IQ anytime I want to do extended bouts of focused work, preparing for podcasts, research, writing grants, and if I ever want to exercise, but I don't have time to eat or I don't want to have my gut full of food. Taking Ketone IQ and thereby increasing my blood ketones allows me to do cognitive work or physical workouts without getting hungry and with plenty of energy and cognitive focus. If you'd like to try Ketone IQ, you can go to HVMN.com/huberman to save 20% off. Again, that's HVMN.com/huberman.

3. 5:41 – 6:31

   The Brain-Body Contract

   1. AHAndrew Huberman5:41

      I'm pleased to announce that I will be hosting two live events in September of 2023. The first live event will take place in Toronto on September 12th. The second live event will take place in Chicago on September 28th. Both live events will include a lecture and a question and answer period, and are entitled The Brain Body Contract, during which I will discuss tools and science related to mental health, physical health, and performance. And I should mention that a lot of that content will have absolutely no overlap with content covered previously on the Huberman Lab Podcast or elsewhere.If you're interested in attending either or both of these events, please go to hubermanlab.com/tour and enter the code Huberman to get early access to tickets. Once again, that's hubermanlab.com/tour and use the code Huberman to access tickets. I hope to see you there. And now for my discussion with Dr. Robin Carhart-Harris.

4. 6:31 – 12:05

   Origin of the Word: “Psychedelics”; Pharmacology

   1. AHAndrew Huberman6:31

      Dr. Carhart-Harris, welcome. I've been wanting to talk to you for a long time. I certainly have known who you are for quite a while because I place you in this very small but very special and important category of researchers who has been pioneering the use of psychedelics for the treatment of specific clinical conditions and really, uh, carrying the torch for essentially the entire field. So I wanna start with a, a voice of gratitude and say thank you for doing this incredibly important work. Could you tell us a little bit about what psychedelics are? In fact, I'm curious as to how the name psychedelic ever came to be-

   2. RCRobin Carhart-Harris7:11

      Mm-hmm.

   3. AHAndrew Huberman7:11

      ... and what you think they potentially reveal about the workings of the brain. And then we'll talk about the clinical applications.

   4. RCRobin Carhart-Harris7:20

      Sure. Well, even that one is, (laughs) uh, is a kind of hot one because, uh, opinions differ on how to define psychedelic. But perhaps a good starting place is to start with the etymology, where did the word come from, and it, it was a Brit (laughs) , excommunicated, uh, living in, in Canada, Humphry Osmond, who, uh, was due to present a, a paper at a National Academy of Sciences meeting on psychotomimetics, drugs that mimic aspects of psychosis in their action. And certain drugs like mescaline, let's see, 1956, and LSD, uh, were on, on the bill and, uh, he felt dissatisfied with them being under this category of psychotomimetics and felt that the signature psychological effects of these compounds went beyond just mimicking psychotic symptoms. And so he wanted to find a more apt term to speak to, in a sense, the principal component of their action. And, uh, he jotted down a few different, uh, possibilities, about a dozen or so I think (laughs) , and one of them was psychedelic, actually, it started, uh, as, and ended up being psychedelic. And, uh, he had a correspondence going on with another Brit also living in the US, Aldous Huxley, uh, where they were playing with some, uh, terms to refer to these compounds. And, and, uh, in the end, uh, Osmond won with psychedelic and he had this little ditty of, um, "To fathom hell or soar angelic, just take a pinch of psychedelic." (laughs) Um, that's where he put the disclaimer in. (laughs) Um, and so, um, what does that mean? It's two ancient Greek words. Psyche means the human mind, or if we're being, uh, actually true to the ancient Greek, it means soul. Um, and then the other component, uh, means to make clear, or to make visible, or to make manifest, or to reveal. So all of those work, um, and it's a, it's a neologism, it's a made up word, but it does have that ancient Greek origin. And it's speaking to this principle that these compounds reveal aspects of the psyche, of the human mind, the soul, that are ordinarily not entirely visible. Um, and so that's the etymology and it's wonderfully poetic, but I happen to think it's also very accurate. It's, uh, a useful term because it's sort of, you might say, valence nonspecific. It doesn't say you're gonna have a great time or that you're gonna go mad (laughs) . Uh, it's more that it reveals the psyche and it could be hellish, but it could be heavenly. Um, and, uh, so that's the etymology and also, a bit of the psychology, um, and sort of, you know, pointing to the phenomenology, the subjective experience. But there's also a pharmacology here. And quite recently, there was put out a consensus statement about psychedelics that's really referring to what we call the classic psychedelics, to say that these are all compounds that work on a particular receptor in the brain, the serotonin 2A receptor, and that's another way that we could define these compounds. I said this one's a little hot because I'm of the view that while the pharmacology is really useful, how the drugs work chemically, you can't avoid the phenomenology. And if we're true to the etymology, where the term came from, then we must recognize and we cannot neglect the subjective experience.

   5. AHAndrew Huberman11:35

      Thank you for that, uh, beautiful description of, uh, what brought us to today in terms of using the word psychedelics and now it's thrown around all the time.

   6. RCRobin Carhart-Harris11:44

      Yeah, too much.

   7. AHAndrew Huberman11:45

      Yeah, too much, and, and I'm guessing, um, well, not guessing, I'm certain that it's, uh, also used to describe many compounds that don't touch the 5H2, 5-HT2A, the serotonin 2A receptor. So, um, there is a broader categorization by most people and, um, it'll be interesting to see where all the nomenclature and naming goes.

5. 12:05 – 17:32

   Psychedelics & Revealing the Unconscious Mind, Psychotherapy

   1. AHAndrew Huberman12:05

      For the time being, I'd love for you to tell us a bit more about this idea that psychedelics, uh, however one defines them, can reveal something about the mind that can't be revealed otherwise. Are-... you talking about the subconscious. I mean, you know, psychologists and most famously Freud, but also Jung and als- also neuroscientists, I think, um, think about subconscious processing. I think, perhaps the most salient example for me that's outside the realm of- of, um, anything psychedelic would be blindsight. This phenomenon that you take people that are blind, but still have some connectivity in their brain and you present them-

   2. RCRobin Carhart-Harris12:43

      Mm-hmm.

   3. AHAndrew Huberman12:43

      ... you know, a board with a computer screen with different number of dots on each side and you say, "How many dots are on each side of the screen?" And they say, "What do you mean? I can't see the screen, I'm blind." And you say, "Well, just guess." And their guess rate is accurate far more than ch- chance would-

   4. RCRobin Carhart-Harris12:59

      Mm.

   5. AHAndrew Huberman12:59

      ... would predict.

   6. RCRobin Carhart-Harris13:00

      Mm.

   7. AHAndrew Huberman13:00

      So they have so-called blindsight and people have said, "Well, this is the subconscious revealing itself." Um, there's no psychedelic drug involved, but what you're describing is a pharmacologic induced state that reveals something that normally, should we assume, is masked or that we are oblivious to, uh, even though it's expressing itself. What- what- what does it mean for these drugs to be re- you know, revealing something about the workings of the mind that would not be obvious to us otherwise?

   8. RCRobin Carhart-Harris13:32

      Yeah. Yeah. So- so the, uh, example of blindsight is interesting, but it's different. Blindsight would be, uh, referring to non-conscious processing, maybe implicit processing. So stuff going on in the mind in perception in a sense that is below the threshold of conscious awareness, but yet is influencing you. So it's sort of, it's kind of related, but it's different. So in in-depth psychology, psychoanalysis, psychodynamic psychology, you know, Sigmund Freud, Carl Jung and so on, um, we talk about the unconscious. Um, and there, it's more about the kind of blood and guts of the human condition, (laughs) the human nature, both the personal unconscious, so things that you might not want to necessarily be conscious of, 'cause it's painful. So that- that's the repression aspect, pushing it out of conscious awareness.

   9. AHAndrew Huberman14:32

      Repressed memories in particular?

   10. RCRobin Carhart-Harris14:33

       Yeah, like traumatic memories, um, difficult, uh, relationships. It could be complex trauma, not necessarily just a specific, you know, index trauma, but a series of traumas. Um, and then you have the collective unconscious, which was really Carl Jung's contribution to say that, um, you know, there's a transpersonal quality to the unconscious. There's aspects about humans, not just this individual human. Uh, there's aspects to our mou- our minds, our psyches that are, um, not fully available to conscious awareness, but can come up in certain states. You know, psychoanalysis went crazy for dreaming as- as their royal road to a knowledge of the unconscious. That was Freud. Um, but, uh, we now know with psychedelics, and this was what drew me into the area, was discovering literature, um, that was speaking to this particular action, the psychedelic action. And we're saying that when these drugs like LSD, psilocybin, uh, found in magic mushrooms, um, when they're used in- in psychotherapy, um, material comes up that maybe may have been repressed, um, that- that, uh, is of, you know, therapeutic value, uh, and awareness and insight of this material seems to catalyze the therapeutic process with, you know, strong emotional release, these cathartic experiences and, uh, and insights. You know, whether they're insights that are personal, um, or whether they're transpersonal. Um, but for me, this is really where the meat of it is with psychedelics and classic psychedelics in particular, the likes of compounds like, uh, LSD and- and psilocybin. I would say that if it wasn't for this action by classic psychedelics, we wouldn't be so interested in psychedelics. I- I think if we only had compounds like ketamine, MDMA, cannabis, then there's, that could be said broadly speaking, to be psychedelic-like. I don't think it necessarily would've captured the world's attention as psychedelics are right now. I- I actually think it's a major gap to fill, is this principle action of the classic psychedelics. What does- what does this mean that I'm referring to psyche revealing? What is that? A- and I suppose where I'm going with this is, what is that in terms of the biology as well? What's going on in the brain and the body when people become aware of things that previously they weren't fully aware of?

6. 17:32 – 26:08

   Microdosing

   1. AHAndrew Huberman17:32

      I'd like to talk about some of the clinical trials that you've been involved with, um, in particular looking at psilocybin, the, as you mentioned, the principle hallu- hallucinatory psychedelic agent in magic mushrooms. Um, I'd like to start with a kind of nuts and bolts question, um, just so that everyone's on the same page. I've read the papers that you've published and that others have published in this area, and typically, uh, the dosages used in these trials are 25 milligrams of psilocybin, and we talk about one recent trial in particular that compared 25 to 10 milligrams to more frequent use of very small amounts, one milligram over three weeks, for instance. However,... when people talk about magic mushrooms, they often talk about gram doses of the mushroom, because I'm assuming that they contain milligram dosages of psilocybin. Here, we're not, um, encouraging, uh, use of any kind. These are clinical trials. But for, um, clarity of understanding, what is the conversion typically? Like one gram of magic mushrooms will contain how many milligrams of psilocybin-

   2. RCRobin Carhart-Harris18:47

      Mm-hmm. Mm-hmm.

   3. AHAndrew Huberman18:47

      ... on average? Because what I w- what I'm trying to do here is, is calibrate people to this idea of microdosing versus macrodosing and that's fairly straightforward to do with respect to the clinical trials. But then in the, a lot of the lay discussion around this, you hear about heroic doses versus microdoses and so (laughs) I think there's a lot of confusion. So, uh, if you would, um, educate us on this, uh, idea of what's a microdose and perhaps also w- how many milligrams of psilocybin are contained in a gram of "magic mushrooms."

   4. RCRobin Carhart-Harris19:23

      Sure. Well, a microdose i- is, uh, neither (laughs) of these are that simple.

   5. AHAndrew Huberman19:27

      (laughs)

   6. RCRobin Carhart-Harris19:27

      But, uh, (laughs) they're fun, uh, it's a fun challenge. The microdose, one definition is that it's a dose of typically a classic psychedelic like LSD or psilocybin, um, that is, uh, that has sub-perceptible psychedelic effects. Like y- it doesn't put you into a noticeable altered state of consciousness that feels like you're tripping. (laughs) Um, and, uh, if that was LSD, it looks as though the threshold is around about, let's see, 10, 11, 12 micrograms. (laughs)

   7. AHAndrew Huberman20:06

      Micrograms?

   8. RCRobin Carhart-Harris20:07

      Micrograms.

   9. AHAndrew Huberman20:07

      Wanna be very clear here-

   10. RCRobin Carhart-Harris20:08

       Yeah.

   11. AHAndrew Huberman20:09

       ... micrograms.

   12. RCRobin Carhart-Harris20:09

       Yeah.

   13. AHAndrew Huberman20:10

       So b- 10, uh, so 10 micrograms of LSD are you saying will not induce visual hallucinations in most people?

   14. RCRobin Carhart-Harris20:17

       So it's, it's, that's threshold level.

   15. AHAndrew Huberman20:20

       Mm-hmm.

   16. RCRobin Carhart-Harris20:20

       That's about the level that, that some people who are sensitive could feel it, um, but if you were to talk to the, uh, microdosing gurus, they might say that that's kind of the ballpark for an LSD dose that you would consider a microdose and then you would take sort of semi-regularly. It, it's typically something like one day on, one day off, or one day on, two days off. This kinda thing. There's different protocols and, um, yeah, so, you know, some, like Jim Fadiman, um, uh, one of the popularizers of microdosing-

   17. AHAndrew Huberman21:00

       (laughs)

   18. RCRobin Carhart-Harris21:01

       ... I think would say that a true microdose should be sub-perceptible. You shouldn't feel it, yet the assumption is it's gonna change you in some way, eh, on a kinda trait level more than a state level, um, and maybe behaviorally. Um, and the typical story goes it will improve wellbeing and maybe, maybe it could improve certain aspects of cognition, say, related to creative thinking. Um, I emphasize the maybe there because that's another angle with microdosing. We're kinda waiting for some compelling evidence. As things stand right now, I'd say we lack, uh, that compelling evidence. There's some suggestive stuff, but often the study designs aren't that strong. It's really hard to do a study with microdosing because you need to have permission to give people a microdose that, you know, for practical reasons, they would go home with and, um, y- otherwise, you, you're requiring them to be in the lab, say, three times a week for X number of weeks to meet the criteria of a course of microdosing, which might be, you know, two or three times a week for, say, a month. And that's a hard thing to do (laughs) in a lab study. It's expensive. You'd need to do that against a suitable control, so a placebo control. And there is a study that's been done in New Zealand, um, that has some interesting preliminary data that did I think kinda did the design right. Um, but, uh, it hasn't been published yet. Um, I've seen some positive findings presented around improvements in, in mood, but it's a bit early to get too excited about that. Um, needs to go through peer review (laughs) and all that. Um, but as things stand, you know, the evidence is pretty thin and, and, you know, we have to be honest about that. We did quite a creative study, uh, with my colleagues at Imperial, the guy leading that, Balazs Szigeti, a Hungarian chap, um, did a really creative design, very much his brainchild. He, um, instructed people to do their own blinding, their own placebo-controlled blinding of their own microdosing. So this was a classic citizen science study, like do it yourself science where they would get their LSD tabs and chop them up, put them into gel capsules, opaque, and have other capsules that are the placebos that they just close, empty capsule. Uh, and then there was a whole barcode scan technique, uh, so that you, uh, you kinda shuffle them up, (laughs) you know? But they've got the barcode in, the QR code, so you can break the code later on, but once you've shuffled them up, you no longer know which ones had, have the, the microdosing and which ones are empty.

   19. AHAndrew Huberman24:09

       Was this LSD?

   20. RCRobin Carhart-Harris24:10

       This was LSD. He also tried it with mushrooms, but the issues with the mushrooms was people would burp sometimes.

   21. AHAndrew Huberman24:16

       Hm.

   22. RCRobin Carhart-Harris24:16

       They'd belch and then they'd have this mushroom taste. So then he instructed people to get some s-... like, non-psychoactive mushroom material to put in. So it's really-

   23. AHAndrew Huberman24:27

       Not an easy study.

   24. RCRobin Carhart-Harris24:28

       Not an easy study. And, and, uh, it was c- I love that kind of science. You know, real creative, first mover kind of science. And the results were fascinating because, um, the short story is that the microdosing didn't, um, compellingly beat the placebo.

   25. AHAndrew Huberman24:46

       It did not.

   26. RCRobin Carhart-Harris24:47

       It didn't. And he controlled, because he asked, uh, he controlled for expectancy. So people's positive expectancy which is, in a sense, the vehicle that carries the placebo response. It's why you have a placebo, is that positive expectancy can drive a therapeutic effect, you know, a large extent. So he measured that pretrial and then used it to kinda correct for the response and how did it work? Those who got a placebo but thought they got a microdose did as well as those who thought they got a microdose and did get a microdose. So it was the bigger effect, the majority of the effect was in thinking that you got a microdose. So in a sense, it was a victory for the power of the placebo response. And it's created all sorts of controversy. People don't wanna believe it, you know, that kind of thing. But that's the beauty of science, isn't it? That science is not about what you want to believe. That right there is the beauty of science, really.

   27. AHAndrew Huberman25:54

       I love that experiment. Uh, kudos to them, um, not going to attempt to say his last name, uh, correctly. (laughs)

   28. RCRobin Carhart-Harris26:02

       (laughs) I tried.

   29. AHAndrew Huberman26:03

       Yeah, yeah.

   30. RCRobin Carhart-Harris26:03

       Probably made a mess of it.
7. 26:08 – 28:28

   Psilocybin vs. Magic Mushroom Doses

   1. AHAndrew Huberman26:08

      you were involved in a, uh, clinical trial that was, uh, published last year comparing 25 milligrams of, um, psilocybin to 10 milligrams of psilocybin, it was a very, um, to, uh, a, a drug called escitalopram?

   2. RCRobin Carhart-Harris26:24

      Yeah.

   3. AHAndrew Huberman26:25

      Yeah.

   4. RCRobin Carhart-Harris26:25

      Lexapro, yeah.

   5. AHAndrew Huberman26:26

      Lexapro.

   6. RCRobin Carhart-Harris26:26

      Mm-hmm.

   7. AHAndrew Huberman26:27

      Um, and this one milligram over a three-week, um, dosage. Uh, i- i- in wanting to discuss the results of that study a bit, um, and some of the other trials that you've done involving psilocybin for depression, the treatment of depression, um, could we calibrate ourselves? 25 milligrams of psilocybin is, uh, is that what one, w- it's gonna be a perceptible dose presumably?

   8. RCRobin Carhart-Harris26:49

      Oh, yeah.

   9. AHAndrew Huberman26:49

      Hallucinations and all that. And is that, uh, what one would find in, um, I'm guessing here, uh, if I'm accurate, this does not mean that, uh, I have experience here but, uh, two, two grams of, of mushrooms-

   10. RCRobin Carhart-Harris27:00

       It's more than that, uh, we think.

   11. AHAndrew Huberman27:02

       Yeah, mm-hmm.

   12. RCRobin Carhart-Harris27:03

       Yeah. Sorry, I missed that, uh-

   13. AHAndrew Huberman27:04

       No, no, no. Go ahead.

   14. RCRobin Carhart-Harris27:04

       ... missed that one. (laughs) Went off on a tangent but, uh, yeah, 25 milligrams of psilocybin would be, we don't know and, and it's important that I say that because I wouldn't want people to hear my answer here and then use it to calibrate their own dosing of mushrooms and get it way off. So it's guesswork and I would love to see someone do a proper study on it and, you know, um, uh, look at the psilocybin content in a given mass of psilocybin mushrooms, magic mushrooms. But to my knowledge, that hasn't really been done. Um, someone like Paul Stamets would, uh, would give a better answer here but, uh, I think the percentage within the mushroom mass is some, of psilocybin in the mushroom mass and psilocin which is the metabolite of psilocybin, um, is something in, in the 1%.

   15. AHAndrew Huberman28:01

       Mm-hmm.

   16. RCRobin Carhart-Harris28:02

       Little bit higher maybe, uh, range.

   17. AHAndrew Huberman28:04

       Okay so one, one gram, 2,000 milligrams of magic mushroom would contain about 10 milligrams of psilocybin.

   18. RCRobin Carhart-Harris28:14

       Broad-

   19. AHAndrew Huberman28:14

       Is that right?

   20. RCRobin Carhart-Harris28:14

       ... broadly speaking, yeah.

   21. AHAndrew Huberman28:15

       Okay. Great. That helps calibrate, um, and I think again, just allows the layperson to, uh, understand a bit more where we're headed with these, uh, psilocybin, uh, trials and, and the results. So,

8. 28:28 – 35:12

   “Psychedelic-Therapy”, Music

   1. AHAndrew Huberman28:28

      eh, we don't have to restrict our discussion to just that one clinical trial but, uh, if we include that one and, and compare to some of the other trials that you've done, I mean, y- your laboratory is seeing phenomenal, in my opinion, phenomenal results in the treatment of, uh, otherwise intractable depression, major depression, which so many people suffer from. From two, um, I, I suppose they're, uh, two sessions of using psilocybin in these ranges of 10 to 25 milligrams. Do I have that correct?

   2. RCRobin Carhart-Harris29:00

      Yes.

   3. AHAndrew Huberman29:01

      Okay. Eh, could we talk a little bit about what people typically experience during those sessions that allows this phenomenal transformation of mood and state and trait, uh, as well? And I'm especially interested in whether or not it is the experience during those sessions that is the trigger that's necessary for the, the transformation from a depressed to a non-depressed state. Because with the, the impulse is to think it is, that what one thinks and sees and hallucinates is, um, and hears, is so vital but of course these drugs can create neuroplasticity, changes in our neural wiring, presumably for long periods of time. So what are your thoughts on the, the experience itself and maybe for those who have not done these compounds before, you could explain a little bit about what's typical for people and what you think is leading to that incredible positive and pervasive change in mood, state, and trait.

   4. RCRobin Carhart-Harris30:01

      Mm. Mm. I would, I would say that it's more than impulse that is, um, leading us to think that the experience is important. It's really data and, and converging evidence now. Um, so independent teams, independent studies are converging on the magnitude of certain kinds of experience, rated, yes, with subjective rating scales, is predicting therapeutic outcomes pretty, pretty strongly and very reliably. Um-... and so that's guiding us. Now, could you say, "Well, maybe those experiences are some kind of epiphenomenon of, say, a central brain action?" Well, absolutely, but then all experience is an epiphenomenon by that principle, and yet we care about it (laughs) , you know, and it matters, uh, to us and in our human relations with each other. So I think it does matter to a, a human being when they're in a, say a psilocybin therapy session, and as the drug effects begin to come on and their body starts to feel a little strange and tingly, and, uh, there's, um, some initial anxiety, and then in their mind's eye, they start to notice patterns and maybe colors, and then maybe those patterns deepen and they're dynamic and they have this fascinating organic quality.

   5. AHAndrew Huberman31:29

      Are they, um, patients in your studies typically using a, um, an eye mask?

   6. RCRobin Carhart-Harris31:35

      Yeah.

   7. AHAndrew Huberman31:35

      Or, so they're in the eye mask, so eyes closed.

   8. RCRobin Carhart-Harris31:37

      Yeah.

   9. AHAndrew Huberman31:37

      That's why you said mind's eye as opposed to looking out into the-

   10. RCRobin Carhart-Harris31:40

       Yes.

   11. AHAndrew Huberman31:41

       ... the, the clinical setting.

   12. RCRobin Carhart-Harris31:41

       And that's one of the major differences to psychedelic therapy versus taking a psychedelic, is you shut your eyes (laughs) , you know? And it's a, it's a world away from taking a psychedelic, yeah, at a rave or something, you know. In a sense, good luck with that. Um, but in psychedelic therapy, yeah, it's, it's, you know, um, settled conditions. Uh, there's music playing. And what I'm describing here is very much the default. Uh, there's, there's actually, you know, very little variability between the different sites that have done this work on these conditions. Um, typically, it's two people, uh, ideally mental health professionals at, at least one who's a psychiatrist or a clinical psychologist or s- some other kind of psychotherapist or psychiatric nurse. Um, but ideally, two who meet those criteria with a individual who's ingested the drug, um, and music playing throughout, a kind of runway into taking the drug and then throughout, so there's continuity.

   13. AHAndrew Huberman32:49

       Uh, music with lyrics or s- or without lyrics?

   14. RCRobin Carhart-Harris32:51

       Without lyrics-

   15. AHAndrew Huberman32:52

       Mm-hmm.

   16. RCRobin Carhart-Harris32:52

       ... to begin with and the music typically is spacious to begin with, um, and then builds and becomes atmospheric. Uh, there might be, I don't know, some tribal drums in the distance or, or something as, as it develops, or like the sound of a bird in the distance, you know, a bird's call. Um, and then as it gets into more stronger drug effects, uh, the music, um, starts to coax, uh, emotion and very intentionally, you know, strings, for example, would come in and, uh, um, it's (laughs) an int- it would be an interesting experiment and one that we'd love to do actually, uh, to see whether if you were to pull that out, whether the, the psychedelic experience would be as emotionally intense as, as it is in psychedelic therapy when you have music there as a default. And across the board, people should find this remarkable because it kind of is. All of the published studies that are now, you know, having such an impact, uh, on psychiatry and beyond have music there as a staple component.

   17. AHAndrew Huberman34:12

       Mm.

   18. RCRobin Carhart-Harris34:12

       And we just take it as assumption that it needs to be. I tend to share that assumption. But it's remarkable that it hasn't been tested properly. But it's there. And, you know, if you were to run with that and, and if you were a, a, you know, had a kind of critical agenda, you would say, "Well, this is music therapy, you know? Uh, why are you making all this fuss about psychedelics when it, it's music that's there in all of these trials with all these fantastic findings." So there is something to that, you know? And y- this will tee me up probably to talk about psychedelic therapy being a combination treatment. Uh, we have a hyphen between the two because I, um, share the hypothesis, uh, the assumption that should be tested better that there is a positive interaction between the two, that there's a synergy between the two. Um-

   19. AHAndrew Huberman35:05

       That's why it's psychedelic therapy-

   20. RCRobin Carhart-Harris35:07

       Yeah.

   21. AHAndrew Huberman35:07

       ... with a hyphen, just like Car- Hart-Harris (laughs) .

   22. RCRobin Carhart-Harris35:11

       (laughs) . Yeah.

   23. AHAndrew Huberman35:11

       Uh.

   24. RCRobin Carhart-Harris35:11

       Yeah (laughs)

9. 35:12 – 36:26

   Sponsor: AG1 (Athletic Greens)

   1. RCRobin Carhart-Harris35:12

      .

   2. AHAndrew Huberman35:12

      I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3

10. 36:26 – 43:01

    Psychedelic Journey: “Trust, Let Go, Be Open”

    1. AHAndrew Huberman36:26

       K2. This is extremely useful to hear because I think most people think, "Okay, psychedelic," whether or not they have experience with psychedelics or not.... get some visual hallucinations, some auditory hallucinations, some synesthesias, some visual auditory blending, um, somatosensation, you know, rubbing a surface and being able to elicit the sounds in one's mind, um, of course, et cetera. But so seldom do we actually hear about the specifics of these clinical trials in a way that, for instance, points to music as one of the perhaps key variables.

    2. RCRobin Carhart-Harris37:00

       Mm.

    3. AHAndrew Huberman37:00

       Now, you mentioned that as people enter these psychedelic states that there's a little bit of initial anxiety. Um, about a year and a half ago, I had a discussion with Dr. Matthew Johnson, who's running some psilocybin trials at Johns Hopkins, as you know, and he, um, mentioned, uh, the critical importance, at least in his mind, to this idea of the patient, quote-unquote, letting go, or allowing the experience to take them some place mentally, as opposed to trying to constrain their sensory and cognitive experience. Uh, I'm curious what your reflections are on that, on that idea, and why it might be so valuable clinically.

    4. RCRobin Carhart-Harris37:46

       Mm.

    5. AHAndrew Huberman37:46

       Um, and this ties back to this earlier dis- discussion we were having about the unconscious, or about psychedelics revealing something that's there all the time, but that we don't have access to. Um, you know, it's, and again, I'm struggling to find the right language for this because we don't really have a neural mechanism like, you know, top-down inhibition or something like that to explain how this, uh, you know, unconscious might be uncorked-

    6. RCRobin Carhart-Harris38:12

       Mm.

    7. AHAndrew Huberman38:12

       ... in the psychedelic experience. But to make it quite simple and direct, how important do you think it really is for the patient to feel like they are, quote-unquote, letting go and what in the world is letting go-

    8. RCRobin Carhart-Harris38:26

       Yeah.

    9. AHAndrew Huberman38:26

       ... in biological terms?

    10. RCRobin Carhart-Harris38:27

        Yeah, yeah. Well, I think we'll get there in terms of having the neural correlates of, uh, the mind revealing itself to itself, you know, the emergence of unconsc- the unconscious into consciousness or unconscious material into conscious awareness. It's a, it's a wonderful challenge, it's a huge challenge, but it's a challenge to embrace. Um, and letting go very much is, again, a staple component of how the different teams do this work in terms of encouraging a willingness to let go. And when we started out doing our depression work and, and did that first trial was the first trial of, of psychedelic in, uh, formally diagnosed depression, you know, where that was the target population, a depressed population. It was the first modern study to do that. And, um, we visited Hopkins, our friends there, and, and were, um, mentored on how to do the guiding, Bill Richards, Mary Cosimano, they were just so, um, brilliant and, and, you know, wise in their, um, in their guidance to us as to how to do the guiding in our trial. And so this phrase of trust, let go, be open, you'll hear a lot. I don't know who fairly it should be attributed to, but I would attribute it to Bill, uh, Bill Richards. M- Yeah, everything's borrowed. He probably got it from someone else, but it's such a key principle and it's almost like a mantra that you're trying to instill in people. Trust, let go, be open and those different components where the trust is about therapeutic rapport that again, you know, this goes beyond just intuition now. We've formally measured therapeutic rapport. We do it even with just a single item, uh, a visual analog scale item, a subjective rating scale item on the morning of dosing, and we find that it's a, it's a significant predictor of the quality of the experience that you have under the drug in the psychedelic therapy, and then the therapeutic outcomes X weeks or months later. Um, it's a very powerful kind of chain of, of sort of predictive components there. But trust, essentially important, and again, not just intuition, but the data pointing to that. Let go, uh, there's a readiness, a readiness to surrender, to let go, to not resist, and we do measure that too and see that it's predictive of response. Um, and then the being open is about a, um, a willingness to go there, to confront, to be inquisitive, uh, something that's easier said than done. Can be terrifying, you know? When you're dealing with a very vulnerable population, uh, it's probably more the rule than the exception that they're carrying some significant adversity, life adversity, or frank trauma that they've suffered. And so that message of be open, be willing to confront and to go there i- is really, you know, it's really powerful. Um, and that's how it plays out. And often there is struggle. There's something going on that is I don't want to be feeling this, make it stop, that can be nightmarish at times, but it's very, very strong and with these big doses that we give, it's, uh, it's very strong. And actually a student, um, that I've worked with, um-... uh, I think, now doing a PhD, uh, Ari Brouwer. Uh, is working on a fantastic project characterizing the different phases of the psychedelic experience, where the early phase is dominated by, um, negative emotions and, and negative, uh, negative valenced feelings of anxiety and struggle. And then it's a different story in the latter half.

    11. AHAndrew Huberman43:00

        Could I

11. 43:01 – 46:21

    Negative Emotions, Fear & Psychedelics

    1. AHAndrew Huberman43:01

       ask about that? Uh, first of all, I think that's fascinating and important to analyze the different phases. And again, I'm delighted here, because people typically hear about a psychedelic journey but we never really hear about the, the kind of stereotypic components of the beginning, middle, and end of that journey. We know that there's a peak and that there's a kind of parachuting down and, um, et cetera but, um, when you say that typically there's an anxiety, maybe some negative valence in the early stage, do you mean about the sensations people are experiencing or about some prior event that's being called to mind that they're remembering? Um, likewise, for the positive phase of the psychedelic, uh, journey or trip, are people... Do they still call it a trip?

    2. RCRobin Carhart-Harris43:42

       Yeah.

    3. AHAndrew Huberman43:43

       All right. For the, uh, I guess... We'll use trip for the psychedelic trip. Are people feeling positive about the experience? Like, "Ah." Like there's been some sort of breakthrough or they're in a, in a calmer state? Or is it that they tend to be focusing on prior events that were positive? So, in other words, is there a threading through of some, uh, concept that comes to mind for people? Maybe about an earlier trauma or maybe about a sense of self or a sense of other forgiveness. Um, you know, it could be any of these things. But, uh, what do we know about that kind of finer details of all that?

    4. RCRobin Carhart-Harris44:19

       Hmm. I would say, the initial, um, struggle is more against the general drug effects than pinning it on, on something specific. It's more that, you know, normal waking consciousness we have a sense, generally speaking if we're well or well enough, a sense of assuredness about what's what. You know, (sound of something hitting the table) there's a table here and so on. (laughs) And, uh, and, and we have that assuredness in-... to an extent about ourselves as well. It might be illusory but we have it. And what the drug's doing is it's breaking down all of that and it's scary as hell, you know? And if it's a big dose, it's just like human nature to be, to r-, you know, rage against that a bit. And a bit like dying, you know? "I don't want this. It feels like I could be dying." Um...

    5. AHAndrew Huberman45:10

       I might lose my mind.

    6. RCRobin Carhart-Harris45:11

       Yeah, that too.

    7. AHAndrew Huberman45:12

       And never come back.

    8. RCRobin Carhart-Harris45:12

       Those two are the classics is, oh, but it, I might, you know, I might know that I've taken a psychedelic and I might even know a, a bit about psychedelics but I still fear that I'm gonna go mad, um, or that I know they, you know, generally speaking these drugs don't have a high, um, you know, fa- fertility, um, uh, risk, uh, I still think I'm gonna die, you know? Um, and it's just, it's very palpable and that, and that comes up. So yeah, that's, that, I mean, those are the core fears that, uh, those two and very reliably that comes up, and it's really, like, a basic drug action. It's dose dependent but it's a basic drug action that is forcing something about the nature of the mind and the way it's made up that makes it feel that way. "Oh, but it feels like I'm losing my mind." Or, "It feels like I could lose my mind or that I could go insane or that maybe I'm, I'm dying here and this is bad." Yeah.

12. 46:21 – 52:33

    Global Functional Connectivity, Serotonin 2A Receptor; Subjective Experiences

    1. RCRobin Carhart-Harris46:21

    2. AHAndrew Huberman46:21

       Uh, you've talked many times before and have done really wonderful work looking at the changes in communication between different brain areas while under the, while people are under the influence of psychedelics and I think the gestalt of those data, correct me if I'm wrong, is that, um, compared to the non-psychodelic state that under psychedelic influence, um, there is far more, let's just call it inter-connectivity or c- uh, communication, um, between a brain areas that typically aren't communicating. Which probably d- is not surprising to people given the, the, um, subjective effects of these, of these drugs. What is the evidence that after the psychedelic journey is over, that some or perhaps all of that enhanced communication across brain areas is maintained?

    3. RCRobin Carhart-Harris47:06

       Hmm.

    4. AHAndrew Huberman47:06

       And if so, what role do you feel that could play in these incredible positive therapeutic outcomes?

    5. RCRobin Carhart-Harris47:13

       Yeah. So we, we've had a, some recent findings in, in that direction where, yes, it's true, and, uh, you know, the, uh, picture that says a thousand words that some people might be familiar with are these two circles. Um, a project that we did in collaboration with s- some researchers where ordinarily the communication is going on, um, within systems like other regions of the visual system will be speaking mostly within the visual system. There'll be a kind of cliquish- cliquishness or a modularity to the quality of the communication in the brain. And then the cool finding with psilocybin was the first, uh, paper is the, the communication. Yes, it sort of transcends these modules and becomes much more inter-modular, um, crossing different, uh, modalities and that effect correlated with the magnitude of the subjective effects and then we replicated it with LSD using different methods and a new paper will come out soon with DMT showing, uh, a similar effect. It's a bit of a debate about what regions are most implicated but the general effect of an increase in global functional connectivity is what we call it, or global communication in the brain...

    6. AHAndrew Huberman48:37

       And this is while under the influence of these drugs?

    7. RCRobin Carhart-Harris48:39

       This is under the influence.

    8. AHAndrew Huberman48:40

       So putting people into a brain scanner-... while they are under the influence of the drug.

    9. RCRobin Carhart-Harris48:45

       Yes.

    10. AHAndrew Huberman48:45

        Is that right?

    11. RCRobin Carhart-Harris48:46

        Yes.

    12. AHAndrew Huberman48:46

        That itself must be a, quite an experience, given that these scanners are small tubes, you're in a bite bar, you, you got a bite bar in your mouth. That's a...

    13. RCRobin Carhart-Harris48:54

        (laughs)

    14. AHAndrew Huberman48:54

        (laughs) Um, quite a, quite a study.

    15. RCRobin Carhart-Harris48:56

        You don't always have a bite bar.

    16. AHAndrew Huberman48:58

        Okay.

    17. RCRobin Carhart-Harris48:58

        At least with the psychedelics. But yeah, you've gotta keep your head still, and uh, and you have the loud, uh, MR scanner noise going. But because it's regular, um, there aren't too many surprises. So it's actually surprisingly tolerable.

    18. AHAndrew Huberman49:15

        And you're in a hospital setting, so you're not worried about what would happen if you had a cardiac event or something.

    19. RCRobin Carhart-Harris49:19

        No, you've got professionals around.

    20. AHAndrew Huberman49:21

        Yeah. Right.

    21. RCRobin Carhart-Harris49:21

        And, you know, most people generally tolerate that setting quite well, surprisingly well. But yeah, we do all that. And, and yes, we do see that, um, opening up of the communication across systems in the brain. And, uh, it does speak to kind of intuition about the subject of experience that, you know, different modalities might be blending with each other.

    22. AHAndrew Huberman49:46

        Is... Uh, s- sorry for interrupting, but I have to ask, is it thought that the activation of the serotonin 2A receptor is what's responsible for the increased communication between brain areas that, under normal circumstances, would not be communicating?

    23. RCRobin Carhart-Harris50:00

        Yes. So there's a few reasons why some modeling work, the computational modeling work that first identifies where the 2A receptor is and then looks at, uh, um, models its basic effect on neural activity, um, will recapitulate the, the, or, um, recreate the effect that we see actually in the data with the scanning. So doing the computational modeling, you can see the same effect by knowing, uh, where the 2A, where the, the key receptors are and then making them do a certain thing that we know psychedelics do.

    24. AHAndrew Huberman50:38

        I can imagine two possibilities and I think it's important to distinguish between these two. One possibility is that the activation of this serotonin 2A receptor leads to increased connectivity and thereby auditory and visual hallucinations emerge, changed patterns of thinking emerge, et cetera. That's sort of the obvious interpretation. But, um, the scientist in me has to ask, is it possible that all of that increased connectivity is occurring and yet that is a distinct phenomenon layered on top of some other effect of the psychedelic drugs impacting access to the s- to the unconscious, hallucinations? In other words, is it the increased connectivity that's leading to this subjective experience or are those two things happening in parallel?

    25. RCRobin Carhart-Harris51:26

        Well, they happen in parallel and they map to each other. But the question of causality, what causes what, uh, is the tricky thing where I, I would suggest that the cir- the, the causality is circular, that they influence each other. And, uh, this gets a bit philosophical, but i- it kind of matters because otherwise, you know, there's a trap that i- it's easy to fall into, uh, where you're thinking that it's all about the brain action causing the subject of experience. And that's typically what we do in cognitive neuroscience. Um, it's kind of like the sort of first port of call kind of materialist, uh, approach. But one can be a materialist essentially, but still appreciate that circular causality that mind also interacts with brain. Um, and it's so hard to pick the two apart, and there is a kind of essential dualism where subject of experience is a thing in and of itself, but that's not to divorce it from what's going on on the biological level.

13. 52:33 – 58:45

    Pharmacology: Therapeutics without Psychedelic Effects; SSRIs

    1. RCRobin Carhart-Harris52:33

    2. AHAndrew Huberman52:33

       The re- the reason I ask is because, um, as I understand it, nowadays there's a bit of a movement within the scientific community that studies psychedelics to develop drugs that can essentially cure or alleviate many of the symptoms of depression or trauma that are built off our understanding of how psychedelics like psilocybin and here I'll throw MDMA in there, although classically not a psychedelic, it kind of gets lumped in. We can get back to that later. But that do not produce hallucinations or massive changes in subjective experience.

    3. RCRobin Carhart-Harris53:11

       Mm.

    4. AHAndrew Huberman53:11

       Actually I think this is what initially got us into conversation on Twitter is I had learned about this paper published out of a group at UC Davis-

    5. RCRobin Carhart-Harris53:18

       Mm.

    6. AHAndrew Huberman53:18

       ... that essentially modifying psychedelics so that they have potential therapeutic application for the treatment of depression, but zero hallucinogenic properties.

    7. RCRobin Carhart-Harris53:29

       Yeah.

    8. AHAndrew Huberman53:29

       And I thought, wow, this is going to be a very controversial thing in the world, right, because the, the history of psychedelics, as you pointed out, has been one of people accessing different modes of thinking, feeling, seeing things, these and letting go, trust, et cetera, a therapeutic relationship. And here we have, um, I don't wanna say pharma 'cause it's not really pharma, but we have laboratories who are trying to, um, tease apart the activation of receptors independent of all that subjective experience in order to essentially ch- treat the same conditions. I'd love for you to comment on this, where you think it might be going, um, and, you know, whether or not you think that's the right or the wrong approach, if it has any validity at all.

    9. RCRobin Carhart-Harris54:10

       Mm. Well, uh, it is pharma, it's just smaller pharma, sort of startup pharma, but-

    10. AHAndrew Huberman54:15

        Okay. So 'cause pharma would like to have drugs that can cure depression but don't make people hallucinate. Is that correct?

    11. RCRobin Carhart-Harris54:19

        Oh, they would. And patients might and the system would love it because the system is used to it. It's medicine.

    12. AHAndrew Huberman54:27

        Right. And it doesn't give this, this, um, uh, mental imagery of, uh, you know, the summer of love in San Francisco or of, of, you know, kaleidoscope eyes, right? Uh, it's, it's more a-

    13. RCRobin Carhart-Harris54:39

        Oh. Yeah.

    14. AHAndrew Huberman54:39

        ... you could imagine the, um, um, more... I have to be careful with my wording here. Um, those who would not be inclined toward that.... would, might, might embrace a therapeutic that, that is strictly effective at treating depression with no hallucinations.

    15. RCRobin Carhart-Harris54:54

        Yeah. And it doesn't look like a, you know, an individual lying on a sofa crying their e- eyes out, uh, um, about, you know, the life that they've lived, um, and that deep catharsis being life transforming. Very different from that model. Um, I'm skeptical of it, um, I, for a few reasons. Um, and one is that I, I can't see the logic. Um, I can't see the pieces fit in a way that's compelling. And I'm also skeptical 'cause I think it could easily be wishful thinking because of that point that patients would like it and the system would like it, and I just, you can't, you gotta bear that in mind as well. Um, so wouldn't it be convenient, you know, if it were true and you could get the therapeutic action without the psychedelic effects?

    16. AHAndrew Huberman55:57

        Well, in a way, that's a little bit of what microdosing seems to be designed-

    17. RCRobin Carhart-Harris56:01

        Yeah.

    18. AHAndrew Huberman56:01

        ... to do. Like you said, take dosages that are below that, that, um, perceptual or s- you know, awareness of some effect threshold over a longer period of time in an attempt to ping the circuits or twist, you know-

    19. RCRobin Carhart-Harris56:13

        Yeah.

    20. AHAndrew Huberman56:13

        ... alter the circuits, but not hallucinate.

    21. RCRobin Carhart-Harris56:15

        Yeah.

    22. AHAndrew Huberman56:16

        Not have a catharsis.

    23. RCRobin Carhart-Harris56:17

        So if, if microdosing can do that and it's sub-perceptible, then microdosing isn't psychedelic action because where's the psychedelic action? When psychedelic when defined means psyche-revealing, you're not getting that effect. You might be getting the pharmacology. You might be getting some direct serotonin to a receptor agonism that could be driving a therapeutic response, but you can get that with SSRIs as well, you know? And so my point is what's, what's new, okay, maybe it's a bit new in people are now developing direct two-way agonists rather than indirect through a serotonin releaser like the selective serotonin reuptake inhibitors, the SSRIs like Lexapro, you know?

    24. AHAndrew Huberman57:03

        Are there any SSRIs that selectively agonize, um, which folks, by the way, means activate in a good way. Ag- agony sounds terrible. Th- those noninformatics might think that mean disrupt, but that can activate the serotonin to a receptor. Are there any drugs that will do that, that are not psychedelic? I'm not aware of any, but then again, I'm not a psychopharmacol-

    25. RCRobin Carhart-Harris57:27

        Well, there are. There are.

    26. AHAndrew Huberman57:28

        ... cologist.

    27. RCRobin Carhart-Harris57:28

        I mean, are there any that are, uh, licensed and used as medicines in psychiatry? I actually had this debate, um, recently on social media and I couldn't see, uh, I couldn't see a compelling example. I saw two-way agonists that we use for other things. You have a compound like Lysuride used in, in treating Parkinson's, but actually it's more of dopamine agonist than anything else.

    28. AHAndrew Huberman57:53

        Right. So they're always hitting other things, right?

    29. RCRobin Carhart-Harris57:55

        They're al- yeah. Yeah.

    30. AHAndrew Huberman57:55

        They're I say tapping other neuro, neuro transmitters.
14. 58:45 – 1:09:14

    Psilocybin & Depression; Long-Term Effects: Connectivity & Neuroplasticity

    1. RCRobin Carhart-Harris58:45

       Now, some of the findings that are being seen that are really exciting, fantastic work being done showing things like increases in the communication components of neurons, dendritic growth, uh, spine growth, uh, synaptic spine growth.

    2. AHAndrew Huberman59:05

       Yeah. By the way, folks, just I'll interrupt for the, uh, not, uh, necessarily spine, uh, the bone, you know, the... Not the cerebral, uh, column, but, um, spines are these little, like little tiny twigs with bulbs on the end of, of neurons that are, allow for communication points between neurons. So neuroplasticity is often associated with growth of dendrites and spines and so forth, which is what, what Robin's referring to. The- that reminds me, and I just wanna make sure that, uh, we close the hatch on the earlier answer because I interrupted you, is the increased connectivity between, or communication between brain areas that's observed while people are under the influence of the psychedelic also observed later after the effects of the drug wear off?

    3. RCRobin Carhart-Harris59:46

       Yeah.

    4. AHAndrew Huberman59:46

       And then I'll just throw in another question there because we're onto this topic now. To what extent do we think that neuroplasticity, structural changes in neurons, functional changes in neurons, are responsible for that, and how long does that last? Let's say I take... Let's say I come into your clinic. I'm a, I'm a subject in your experiment. I take, do... Come in in the morning, I do my psychedelic journey five or six hours later, I'm parachuting back to reality as we call it, and then I go home. Increased connectivity lasts for how long, and how long are the structural brain changes occurring?

    5. RCRobin Carhart-Harris1:00:23

       Hmm. Well, you're asking fantastic questions, and, and partly because we don't have the answer yet, but we do have some, we do have some data. And so we have looked at, first of all, the, in a sense, the functional plasticity or what we assume it to be, or at least the functional changes, the increase in communication across systems, um, that increase in global connectivity, functional connectivity. Do we see it after the trip? We know we see it during the trip pretty well replicated correlating with intense drug effects. Do we see it after the trip? Well, the answer is we've seen it in two different depression cohorts, psilocybin therapy for depression. In one study where we look the next day.... we saw it, a kind of residual, um, uh, effect similar to what you see acutely s- being seen the next day. And then in a subsequent study, we saw it also three weeks later. So we've seen it in two independent data sets. This decrease in modularity is how we measure it. It's the same thing, essentially. Broadly speaking, it's the same thing. An increase in global connectivity, functional connectivity. And actually, unpublished, we've seen it in healthy volunteers on a correlational level, not on an absolute change level. But if you look at its relationship to a mental health outcome, and this is an important thing to stress with the depression work, we saw a relationship between the magnitude of that change, the decrease in modularity or increase in global connectivity, and the improvement in symptom severity.

    6. AHAndrew Huberman1:02:04

       So interesting.

    7. RCRobin Carhart-Harris1:02:06

       Yeah.

    8. AHAndrew Huberman1:02:06

       I mean, what I, and just to state it a different way, so, um, what Robin's referring to is when you say r- modularity, as neuroscientists, we think of the, the different modular networks of the brain that, you know, the eye talks to a region of the thalamus involved in vision, which talks to the visual cortex, which, you know, eventually converges w- with auditory information, of course. Um, but there's a separation or modularity of function. This increased connectivity is cross-modular in, during the trip, but afterwards as well. And you're saying that that correlates very strongly with the strength of the therapeutic outcome-

    9. RCRobin Carhart-Harris1:02:40

       Yeah.

    10. AHAndrew Huberman1:02:40

        ... for depression. I mean, the, the logical extension of that is that extreme modularity of brain function is, um, depressive in some way. Now, we don't wanna go t- too far, but what does that mean, that increasing crosstalk, um, between different modules of the brain is so strongly correlated with a positive therapeutic outcome?

    11. RCRobin Carhart-Harris1:03:03

        We don't know other than that there's a relationship. I mean, this is, this is the thing. We need to be a little careful not to run with it too far. I mean, there's some things that it suggests. I think it suggests a more flexible, uh, mode of brain functioning if you're not getting stuck in modules or the modules aren't, um, excessively cut off from each other. But you see different things with, with different presentations. If you were to look at cognition, sharper cognition is actually associated with more modularity.

    12. AHAndrew Huberman1:03:40

        Mm-hmm.

    13. RCRobin Carhart-Harris1:03:41

        So it d- it's a rule that's a little slippery, and we need to be careful with it.

    14. AHAndrew Huberman1:03:46

        I, I, I just, uh, again, I'll, uh, forgive me for interrupting, but I think of, I have friends who are, um, I would say are on the spectrum, who are, um, very linear in their thinking and extremely intelligent in a c- in the kind of classic sense of being able to w- ratchet through hard problems to arrive at a solution. And then I have friends who are, let's just call 'em what they are, from the creative communities outside of science, that, um, are very expansive. Um, they see c- connections between many different things. But you, sometimes you have to, not all of them, but you have to catch their ideas with a butterfly net. And oftentimes, what they're saying doesn't... sometimes just doesn't make any sense. Now, they also produce incredible creative works. But to have a conversation with them is anything but a linear experience. They are not random thought generators. Um, but there's a non-linearity or randomness to their processing that's distinct from these other folks that I'm describing as on the spectrum. And of course, it's a spectrum. There's some, a, a whole range in between.

    15. RCRobin Carhart-Harris1:04:46

        Yeah.

    16. AHAndrew Huberman1:04:46

        Um, it sounds to me like there is some therapeutic value to being able to move along this continuum from the more linear to the non-linear.

    17. RCRobin Carhart-Harris1:04:55

        Yeah.

    18. AHAndrew Huberman1:04:55

        Is that, is that correct?

    19. RCRobin Carhart-Harris1:04:56

        Well, I think so. Um, yeah. Yours, y- it's resonating what you're saying, and speaking to my intuition that, you know, uh, you could be very parse-y, you know, parsing things up, chopping things up like an analytical scientist-

    20. AHAndrew Huberman1:05:10

        A splitter.

    21. RCRobin Carhart-Harris1:05:11

        ... like I'm doing a bit.

    22. AHAndrew Huberman1:05:11

        A splitter, as we say in science. You're either a lumper or a splitter. Yep.

    23. RCRobin Carhart-Harris1:05:15

        Or, you know, or the way I'm being very particular about what, wha- when to call something psychedelic, you know, that, that kind of parse-y analytical way of thinking you would, you might associate with a more modular system, you know. Um, whereas the system that's more globally interconnected and open, yeah, might be more flexible and creative and divergent in the associations and so on. So yes, that's speaking to my intuition too, how you, you're describing it. And I imagine if you take severe psychopathology, severe mental illness, like a depression, I've always thought that there's something intuitive about the term itself, like a depression in a landscape, you know, which is a whole-

    24. AHAndrew Huberman1:05:58

        Physical depression.

    25. RCRobin Carhart-Harris1:05:59

        A physical depression-

    26. AHAndrew Huberman1:06:00

        Mm-hmm.

    27. RCRobin Carhart-Harris1:06:00

        ... that it's easy to fall into. And if you do, it's hard to get out of.

    28. AHAndrew Huberman1:06:05

        So almost, um, if I understand what you're saying correctly, almost like getting, um, stuck at one location on this continuum because most people don't reside at one or extreme, one extreme or the other full time, and kind of migrate back and forth between expansive states-

    29. RCRobin Carhart-Harris1:06:20

        Yeah.

    30. AHAndrew Huberman1:06:20

        ... and more linear states.
15. 1:09:14 – 1:10:26

    Sponsor: LMNT

    1. RCRobin Carhart-Harris1:09:14

    2. AHAndrew Huberman1:09:14

       I'd like to just take a brief break and thank one of our sponsors, which is LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means plenty of salt, sodium, magnesium, and potassium. The so-called electrolytes and no sugar. Now, salt, magnesium, and potassium are critical to the function of all the cells in your body. In particular, to the function of your nerve cells, also called neurons. And we now know that even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance. LMNT contains a science-backed electrolyte ratio of 1,000 milligrams, that's one gram, of sodium, 200 milligram of potassium, and 60 milligrams of magnesium. I typically drink LMNT first thing in the morning when I wake up in order to hydrate my body and make sure I have enough electrolytes, and while I do any kind of physical training and after physical training as well. Especially if I've been sweating a lot. And certainly, I drink LMNT in my water when I'm in the sauna and after going in the sauna, because that causes quite a lot of sweating. If you'd like to try LMNT, you can go to DrinkLMNT, that's L-M-N-T.com/huberman, to claim a free LMNT sample pack with your purchase. Again, that's DrinkLMNT, L-M-N-T.com/huberman.

16. 1:10:26 – 1:12:56

    Psilocybin Therapy & Anorexia

    1. AHAndrew Huberman1:10:26

       Would you say that's right? The one or two or three sessions, and how, how far apart are those typically spaced in time?

    2. RCRobin Carhart-Harris1:10:33

       Yeah. Typically, one, two, three weeks, uh, across the sites is the way people are doing the, the psychedelic therapy dosing sessions. Two sessions, uh, you know, Hopkins, Imperial, NYU, um, that's, uh, been a kind of default to, we, we actually use three in a current anorexia trial, psilocybin therapy for anorexia. Um, two patients left t- to, to see after, um, 19 who've gone through the trial. Very exciting results there, um-

    3. AHAndrew Huberman1:11:07

       You're seeing a alleviation of the, the obsessive thought about food, r- and a willingness to consume-

    4. RCRobin Carhart-Harris1:11:13

       Wait, even-

    5. AHAndrew Huberman1:11:13

       ... healthier amounts of food?

    6. RCRobin Carhart-Harris1:11:14

       Yeah. Even im- improved weight, uh, at the long follow-up, so.

    7. AHAndrew Huberman1:11:19

       So critical. I when, we did an episode on eating disorders and I learned that, uh, anorexia nervosa, which by the way folks, the rates of are not increasing. It's been pretty stable through time, despite what's said about social media and, uh, et cetera. But, um, anorexia nervosa being the most deadly of all psychiatric illnesses, which is a big statement because, you know, uh, manic depression, so-called bipolar depression has a 20 to 30 times the, the typical suicide rate. Uh, basically, many anorexic or people with anorexia I think is how it's now, uh, is what one says, not anorexics, but people with anorexia, um, often die.

    8. RCRobin Carhart-Harris1:12:01

       Yeah.

    9. AHAndrew Huberman1:12:01

       Many of them die.

    10. RCRobin Carhart-Harris1:12:02

        Yeah. Yeah. So tragic. So often young people as well. And similarly with suicide in terms of premature death. So the tragedy with psychiatry is s- so strong and, and there. So it's, it's so rewarding to be doing that trial and to be seeing good results. I have to check myself a little bit that, um, I'm, I'm reporting on it in this really promisory way and, uh, the trial isn't yet publicly released and, and published, so, um, it's still ongoing as well.

    11. AHAndrew Huberman1:12:34

        But that was three d- three sessions.

    12. RCRobin Carhart-Harris1:12:36

        It is three sessions, and I can't say what the dosage is because we still have, um-

    13. AHAndrew Huberman1:12:41

        Mm-hmm.

    14. RCRobin Carhart-Harris1:12:41

        ... there is a blinding component, um, but there are three dosing sessions in there. Let's see now. I think they're two weeks apart. Um, and we do the follow-up, um, yes.

17. 1:12:56 – 1:19:50

    Integration Phase & Psychedelic-Therapy; Meditation

    1. RCRobin Carhart-Harris1:12:56

    2. AHAndrew Huberman1:12:56

       Um, I'd like to kind of close out this, uh, description of the, of the journey and the trip by extending past the day when, uh, people actually take the drug into this, uh, what I've heard described as the integration phase. You know, you have to reintegrate, right? I mean, all this lo- all this increased connectivity during the session, hallucinations, insights, anxiety, letting go, maybe-... revelation, maybe epiphany. Okay, great. At what point is that consolidated? Meaning, um, are these patients, subjects in studies, having daily conversation with their therapist? Are they journaling every day? Uh, and, you know, I want to keep in mind that most people are not going to be part of a clinical trial. And of course here, we're not suggesting what people do or not do. But let's just put it this way, um, were people to, uh, use psychedelics, w- what is the way that people can maximize on the neuroplasticity and the brain changes in a positive way in the days and weeks afterwards? In other words, how long does this so-called integration last? And, you know, what, how far can we take this? I mean, I could imagine that, um, how often one chooses to think about the insights could also have an impact.

    3. RCRobin Carhart-Harris1:14:15

       Yeah.

    4. AHAndrew Huberman1:14:15

       Right? Because clearly people went to raves, clearly people did psychedelics in the '60s. Uh, we don't know if, uh, clearly people do psychedelics now, but we don't have data on those people. You have access to the understanding of how they're spending their time and the therapeutic outcomes, which we haven't gotten to the numbers yet, but, uh, again, are, are incredibly impressive. You know, in upwards of, as I understand it, 60% or more of people getting re- uh, relief from depression.

    5. RCRobin Carhart-Harris1:14:41

       Yeah. 70, yeah.

    6. AHAndrew Huberman1:14:42

       70%. Incredible, especially when compared to the typical, uh, antidepressant treatments and, and so on. So, what is this business of integration? How is it done properly?

    7. RCRobin Carhart-Harris1:14:55

       Yeah. Yeah. Gosh. Well, how long does it last as well? Um, a lifetime. Uh, you know, life is a journey, like a trip is a, a journey, um, and there's always work to do, you know, as Jack Kornfield says, "After the ecstasy, the laundry." And, you know... (laughs)

    8. AHAndrew Huberman1:15:14

       I love that.

    9. RCRobin Carhart-Harris1:15:14

       Yeah.

    10. AHAndrew Huberman1:15:15

        Yeah.

    11. RCRobin Carhart-Harris1:15:15

        There's, there'll be other good ones as well-

    12. AHAndrew Huberman1:15:17

        (laughs)

    13. RCRobin Carhart-Harris1:15:17

        ... but I forget them. Um, but, uh, yeah, so the work's ongoing and, and, and there, yeah. Um, but this gives you a foot up. It enables people to, um, do the work more easily and, and that's true of the classic psychedelics. It's also true, very true of MDMA therapy, uh, for post-traumatic stress disorder. It's really giving you a leg up, making it easier to do very, very difficult work, going back to a trauma, trying to digest it, process it, integrate it. Um, so it's such an essential component of the treatment model. Um, but one has to be realistic as well s- you know, by saying, "Oh, integration lasts a lifetime," well, people delivering a service can't be there for a lifetime. So, um, what's the answer there? Um, and, uh, people are wrestling with that issue right now, um, and I, I think one of the solutions might be that it, it's in a sense on you, uh, to a point, you know? Uh, the therapeutic team can treat you to a point and then it becomes what you might call practice in a similar way that meditation is a practice. It's something that you have to keep up and if it slips, then things could slip, and, and that's the way it is. Um, or you have a, um, another psychedelic treatment, you know? So people have even used this term of practice in relation to psychedelics where there's a psychedelic practice, like there's, you know, a meditation practice. But, uh, I'm using meditation, um, intentionally here because they actually think that, um, meditative practice, um, spiritual practice, elements of spiritual practice could be a very important complement to psychedelic therapy. Uh, and I think it's probably doing something similar in terms of promoting an ability to sit with. Uh, a, uh, former colleague of mine said it quite well in relation to psychedelic therapy versus chronic pharmacotherapy or like SSRIs, being on them all the time. He says, "Psychedelic therapy allows you to sit with rather than sit on." And I thought, "That's quite good." Um, yeah, so, you know, the meditation, the mindfulness, um, the ability to, yes, be present-centered but also present-centered and accepting, so if things come up, you can watch and process and then let go. Um...

    14. AHAndrew Huberman1:18:07

        That holy grail of m- of mindfulness.

    15. RCRobin Carhart-Harris1:18:09

        Yeah.

    16. AHAndrew Huberman1:18:10

        You know? Uh, you know, awareness without reactivity, respond... Uh, you know, I, I grew up in the Bay Area and you'd hear this language, right? And I'm not being disparaging of this. I have friends that are on the board of SLN and work down there, you know, and I've gone there and it's, you know, and yet you hear these terms, right? Be responsive, not reactive, which to a neuroscientist is like, grates on me, which probably just means I have issues. But, um, and surely I do. But, you know, it's like, what does that mean, right? It's sort of saying like, oh, to, uh, be the observer but not be drawn into the experience. You know, and, and again, uh, I don't want to be overly reductionist, but w- what I find so compelling about the emerging data, 'cause it really is data, on psychedelics as treatments for depression and trauma, namely psilocybin and MDMA, is that it really seems to allow people this space that-

    17. RCRobin Carhart-Harris1:19:04

        Yeah.

    18. AHAndrew Huberman1:19:05

        ... that is so commonly thrown around, you know, giving space between stimulus and reaction. I mean, Victor Frankl talked about this. But, you know, it's t- I'd been reading a wonderful book called The Prince of Medicine. It d- dates back to the origins of medicine. Very dense book. People have been talking about this stuff and thinking about this stuff for thousands of years.... psychedelics seem to give people access to that better version of self...

    19. RCRobin Carhart-Harris1:19:27

        Mm-hmm.

    20. AHAndrew Huberman1:19:27

        ... which is remarkable. What's also remarkable, it's per- perhaps worth pointing out, is that five years ago, I never would've been comfortable having this conversation. I would've been afraid to lose my job. Stanford Magazine this week just published an entire issue about psychedelics with how ketamine works, MDMA, psilocybin, with the appropriate cautionary notes in there. But clearly times are changing. Speaking

18. 1:19:50 – 1:30:16

    First-Time Psychedelic Use, “Entropic Brain Effect”, Neuroplasticity, Cognition

    1. AHAndrew Huberman1:19:50

       of which, I know you're doing a trial on first time use of psychedelics.

    2. RCRobin Carhart-Harris1:19:56

       Mm-hmm.

    3. AHAndrew Huberman1:19:57

       What inspired that and what are you observing? And as you tell us that, please give us, um, a few of the, the key contours. Uh, what's the dose, um, how old are these subjects? I'm assuming it's men and women. Are they suffering from depression or not? Like kind of what, what's the landscape of that study. And I, I, I realize this is still early days of the study or maybe it's close to completion. It's not yet published, however, correct?

    4. RCRobin Carhart-Harris1:20:21

       It's not, it's not published, it's not submitted. It is completed.

    5. AHAndrew Huberman1:20:25

       Great.

    6. RCRobin Carhart-Harris1:20:25

       So this was one o- another one of our COVID studies in a sense.

    7. AHAndrew Huberman1:20:28

       Mm-hmm.

    8. RCRobin Carhart-Harris1:20:29

       Meaning COVID hit and we had to finish the study, and it was hard to finish the study because of COVID. That was true of our psilocybin therapy versus escitalopram, uh, Lexapro trial, um, uh, which is published, New England Journal of Medicine, but the-

    9. AHAndrew Huberman1:20:45

       This was 20... That paper, by the way, folks, we'll provide a link to in the show note captions, as well as some of Robin's other, uh, papers. Uh, I think that 2022 New England Journal paper is really fabulous, uh, given it's the different dosages and the comparison to essentially what is microdosing and the comparison to citalopram.

    10. RCRobin Carhart-Harris1:21:02

        Mm.

    11. NANarrator1:21:03

        Yeah.

    12. RCRobin Carhart-Harris1:21:03

        Yeah, that's interesting that you, you link the way we gave small doses of psilocybin to microdosing. We didn't think of it that way.

    13. AHAndrew Huberman1:21:10

        Mm-hmm.

    14. RCRobin Carhart-Harris1:21:10

        We thought it was just a, a necessary placebo-

    15. AHAndrew Huberman1:21:15

        (laughs)

    16. RCRobin Carhart-Harris1:21:15

        ... for the big, big dose.

    17. AHAndrew Huberman1:21:16

        Right.

    18. RCRobin Carhart-Harris1:21:16

        The 25 milligrams. But, uh, yeah, and so that we could say to everyone we're giving you psilocybin and not be lying. Yeah, for those who got escitalopram, Lexapro for six weeks, they, they got a very, very low dose of psilocybin. But it allowed us to standardize all the psychotherapy and so on.

    19. AHAndrew Huberman1:21:34

        Mm-hmm.

    20. RCRobin Carhart-Harris1:21:34

        But the, the other study that you're referring to, uh, was in healthies, healthy volunteers, um, middle-aged, um, average age I think was 40. So not your typical student study that is so often the case in psychology research, you know, all, all the undergrads (laughs) end up volunteering for your study. Uh, so this is, um, uh, more, more of an age range and also I think it was an equal proportion of male and female. All the staff actually were female, which the staff were very proud of 'em.

    21. AHAndrew Huberman1:22:06

        Although it produces its own potential confound, right? To have, uh, all one, one sex of, of, of staff.

    22. RCRobin Carhart-Harris1:22:14

        Possibly.

    23. AHAndrew Huberman1:22:14

        Yeah.

    24. RCRobin Carhart-Harris1:22:15

        They did a good job-

    25. AHAndrew Huberman1:22:16

        Uh-huh.

    26. RCRobin Carhart-Harris1:22:16

        ... in the sense that, um, we saw significant improvements in well-being at the end of the trial. So let me describe the design. It was a repeated measures design, meaning people come in, you collect your baseline data and do a brain scan, and you give people, um, a placebo. We gave people a placebo, and actually let me rewind a little bit. Everyone's healthy volunteers, middle-aged, never taken a psychedelic in their life, none of them, entirely, you know, fresh, virgin people coming in. And, uh, and the plan is to give them their first ever psychedelic experience. So that's what we did in this study. But to do it, we have this repeated measures design where they'll first get a placebo, and we have the placebo so that we can do all the procedures, all the therapy, all the music listening, but not give a whopping dose of psilocybin. We, again, we gave them a placebo dose of psilocybin, one milligram. We stick EG, uh, headsets on during the experience to record the brain activity, um, from the scalp, uh, the oscillating electrical activity, and we do the MRI scanning, um, before and after to see deeper into the brain. And we can look at the functional connectivity that we were referring to earlier, and also properties of brain anatomy, which we did in this study. So the sh- the short story is that all of the changes that we saw both psychologically and neurobiologically were seen with the 25 milligrams. It all happened with that big whopping dose. And what did we see? Well, we did see significant improvements in psychological well-being. We saw what I call the entropic brain effect, which is actually formally quite a- accurate. We see an increase in the informational complexity of ongoing brain activity recorded with EEG on the dose of psilocybin. The activity becomes more complex. It's harder to predict across time. It's more informationally rich, and that effect correlates as it does very reliably with the magnitude of the subjective effect. So the bigger the trip, the bigger this entropic brain effect. Um, now pretty well replicated finding. Um, but then the MR, the MRI, um, seeing deep into the brain was probably our most exciting result, where we didn't just see some functional brain changes, but we've seen some anatomical brain changes as well. And we used a technique called diffusion tensor imaging that looks at the cabling of the brain, the white matter tracts. And we saw a change in major tracts, so we, we sort of limited our search base to really thick tracts, um, really thick fibers. And the fibers that came through as changing were ones that traveled between the prefrontal cortex and, and the thalamus and the striatum, um...... there were two tracks, two prefrontal tracks that changed, and they changed in the direction of the decrease in axial diffusivity, which, um, could be interpreted as tracked integrity, where a decrease would be an increase in tracked integrity. It is something that you see in the developing brain, the axial diffusivity decreases as a brain goes from being a baby to being a adult, axial diffusivity goes down, and then in aging and pathologies of aging, axial diffusivity goes up. So we've-

    27. AHAndrew Huberman1:26:03

        This is in the opposite direction of, of the results you talked about earlier in terms of brain connectivity of a sort of increased communication across areas. If I understand correctly, and I'm perfectly happy to be wrong, by the way, that this decrease in axial, um, diffusivity is, translates to a higher fidelity of communication between the prefrontal cortex and the thalamus and striatum as opposed to less, and, uh, your description of this is somewhat like the, the, um, transition from babyhood and childhood to adulthood, um, speaks to the same where we know that there's a massive culling of connections as opposed to growth of connections, so in other words, as we get older, we get better at doing certain things and less good at doing potentially most everything else.

    28. RCRobin Carhart-Harris1:26:49

        Mm.

    29. AHAndrew Huberman1:26:50

        Is that right?

    30. RCRobin Carhart-Harris1:26:52

        Ish, because the, the change was anatomical, um, and not functional. So the other stuff was, is really measuring, um, communication in, in the brain by looking at how the activity fluctuates across time and whether those fluctuations in activity are synchronous between regions, and if they are, we say they're functionally connected and we infer that they're talking to each other 'cause they go up and down in synchrony. But when it comes to the anatomy, we're talking about the just static, you know, material stuff, and, uh, um, so we're seeing the fibers and a property of the fibers change. Um, at least that's what we think. (laughs) And recently, we had an independent person come in and reanalyze the data 'cause, you know, one of those things, incredible finding requires, you know, credible (laughs) -
19. 1:30:16 – 1:38:55

    Fibromyalgia & Psychedelic Treatment; MDMA Therapy & “Inner Healer”

    1. AHAndrew Huberman1:30:16

       I want to hear a bit about the study that you have been carrying out on the use of psilocybin for the treatment of fibromyalgia. Uh, I'm intrigued by fibromyalgia, uh, 'cause, because I have a good friend who also... I won't reveal who it is, and, and no, it's not me. This isn't the "I have a friend" thing. Who also is a scientist who's, um, uh, sits in a fairly high position in the National Institutes of Health, who, um, quietly has expressed to me that they are incredibly frustrated with the fact that, um, the standard medical community has, um, largely ignored fibromyalgia, um, and that for many years it was kind of lumped with things like chronic fatigue syndrome and other, um, so-called... Again, so-called, I'm not saying this, but, uh, people often refer to these as, "Oh, it's psychosomatic. That's all in your head," which as a neuroscientist, this is a ridiculous statement to hear because it's all in your head. Your brain is in your head after all. Your physiology and your psychology are influencing each other, of course, and, and the, the world is starting to appreciate that more. But first of all, um, maybe you could tell people what fibro- myalgia is, what inspired you to do a study on fibromyalgia?... using psilocybin of all things, um, 'cause that's surprising to me. And, um, if you m- are allowed to or if you have access to the data in, um, in mind, uh, share with us a little bit about what you're discovering in that, in that study.

    2. RCRobin Carhart-Harris1:31:40

       Sure, yeah, happy to. So, again, it's psilocybin therapy and the population is fibromyalgia syndrome. So this is people presenting with a generalized chronic pain. So unlike some other pain disorders where the pain is focused, you can say, "It's my lower back," which is very common, uh, chronic lower back pain, this is more generalized. And it, and for that reason, it's hard to sort of know what it is. And, and that's why it's been a controversial space in medicine, and it's been, yeah, it's had that charge thrown at it that maybe it's psychosomatic, and just to your point, um, is anything ever, you know, independent of, of the mind anyway? But this is actually a fascinating space for how, you know, subjective experience, the lived experience, and the mind can influence the body, because there's some really interesting literature around the etiology, like the, h- how the pain has come about, in a sense like, what caused the pain? What's the story there? And ahead of the trial, I would say to my colleagues, "Let's just be careful, because there is some fascinating literature around things like, um, a background of trauma and, um, how, um, uh, e- that can relate to issues r- related to inflammation and how that can express into things like fibromyalgia syndrome." I just said, "Be very careful there, because if you go in with an assumption that there's some buried trauma, for example, then there's that whole other side of psychoanalysis that massively tripped it up around false memory and so on. And so please don't hold prior assumptions that you're gonna uncover, um, buried trauma in every case." Now, the team have treated, I think, eight people, um, and it's going, it is going very well. Again, I just wanna be careful with how I describe it to ma- you know, to manage expectations and not get too carried away. But, uh, I check in with the team every week, and, um, they're still based in London doing the work. Um, and, uh, it's remarkable what I hear about the profound experiences that people have under the drug. In this study, we only give one dose. It's a very mechanistic study. We actually have the EEG cap on in the sessions, um, like in the healthy volunteer study, but this time, now taking it into a clinical population. And, uh...

Episode duration: 2:37:08