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

30:54There's actually you know, very little variability between the different sites that have done this work on these conditions. Typically it's two people, ideally mental health professionals at least one who's a psychiatrist or a clinical psychologist or some other kind of psychedelic therapist or psychiatric nurse. But ideally two who meet those criteria with a individual who's ingested the drug and music playing throughout, kind of run way into taking the drug and then throughout. So there's continuity music with lyrics or without lyrics to begin with and the music typically is spacious to begin with and then builds and becomes atmospheric.

31:49There might be I don't know some tribal drums in the distance or something as it develops or like the sound of a bird in the distance, you know, a bird's call. And then as it gets into more stronger drug effects, the music starts to coax emotion and very intentionally, you know, strings, for example, would come in and it would be an interesting experiment of what we'd love to do actually to see whether if you were to pull that out, whether the psychedelic experience would be as emotionally intense 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.

32:44All of the published studies that are now, you know, having such an impact on psychiatry and beyond, have music there as a staple component. 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 that. And, you know, if you were to run with that and if you were, you know, had a kind of critical agenda, you would say, well, this is music therapy, you know, why are you making all this fuss about psychedelics? 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 this will team me up probably to talk about psychedelic therapy, being a combination treatment.

33:34We have a hyphen between the two because I share the hypothesis, the assumption that should be tested better, that there is a positive interaction between the two, that there's a synergy between the two. That's why it's psychedelic therapy for the hyphen, just like heart, heart, heart. 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 to be the probiotics that I need for gut health.

34:23Our gut is very important. It's populated by 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. Those probiotics and 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 atletitgreens .com slash 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 and the car on the plane, etc.

35:01And they'll give you a year supply of vitamin D3K2. Again, that's atletitgreens .com slash Huberman to get the five free travel packs and the year supply of vitamin D3K2. This is extremely useful to hear because I think most people think, okay, psychedelic, whether or not they have experience with psychedelics or not, it gets a visual hallucinations, some auditory hallucinations, some synesthesia, some visual auditory blending, some atticensation, rubbing a surface and being able to elicit the sounds in one's mind, of course, etc. 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.

35:45Now, you mentioned that as people enter these psychedelic states that there's a little bit of initial anxiety. Out 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 mentioned 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 someplace mentally, as opposed to trying to constrain their sensory and cognitive experience. I'm curious what your reflections are on that idea and why it might be so valuable clinically. And this ties back to this earlier 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.

36:43And 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 unconscious might be uncorked 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 in biological terms? Yeah, yeah. Well, I think we'll get there in terms of having the neural correlates of the mind revealing itself to itself, you know, the emergence of unconscious, the unconscious into consciousness or unconscious material into conscious awareness.

37:32It's a wonderful challenge. It's a huge challenge, but it's a challenge to embrace 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 did that first trials, the first trial of psychedelic in formerly diagnosed depression, where that was the target population and depressed population. It was the first modern study to do that. We visited Hopkins, our friends there and we're mentored on how to do the guiding, Bill Richards, Mary Cosimano, they were just so brilliant and you know, wise in their guidance to us as to how to do the guiding in our trial.

38:40And 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, Bill Richards, everything's borrowed, you probably got it from someone else, but it's such a key principle. It's almost like a mantra that you're trying to instill in people's trust, let go be open. And those different components where the trust is about the therapeutic rapport, that again, you know, this goes beyond just intuition now, we formally measured therapeutic rapport, we do it even with just a single item, a visual analogue scale item, a subjective rating scale item, on the morning of dosing, and we find that 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.

39:46So very powerful kind of chain of predictive components there, but trust, essentially important, and again, not just intuition, but the data pointing to that. Let go, 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. And then the being open is about a willingness to go there, to confront, to be inquisitive, something that's easier said than done, can be terrifying, you know, when you're dealing with a very vulnerable population, 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.

40:44And so that message of the open, be willing to confront and to go there, it's really, you know, it's really powerful. 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 nightmare -ish at times, but it's very, very strong, and with these big doses that we give, it's very strong. And actually, a student that I've worked with, I think now doing a PhD, Ari Brower, is working on a fantastic project, characterizing the different phases of the psychedelic experience, where the early phase is dominated by negative emotions and negative, negative, evalanced feelings of anxiety and struggle, and then it's a different story in the latter half.

41:45Could I ask about that? 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 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 a parachuting down, and, et cetera. But 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?

42:20Likewise, for the positive phase of the psychedelic journey or trip, are people, do they still call it a trip? All right, for the, 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 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, you know, it could be any of these things?

43:00But what do we know about the kind of finer details of all that? I would say the initial 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 assuridence about what's what, you know, as a tailoring and so on. And we have that assuridence to an extent about ourselves as well. It might be a looserie, 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 to, you know, rage against that a bit and a bit like dying, you know, I don't want this.

43:52It feels like I could be dying. I might lose my mind. Yeah, those two of the classics is, oh, but I might, you know, I might know that I've taken a psychedelic and I might even know a bit about psychedelics, but I still fear that I'm going to go mad. Or that I know that, you know, generally speaking, these drugs don't have a high, you know, fertility risk, I still think I'm going to die, you know, and it's just, it's very palpable and that comes up. So yeah, that's, I mean, those are the core fears that 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.

44:54Oh, 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 dying here and this is bad. Yeah. You've talked many times before and have done really wonderful work, looking at the changes in communication between different brain areas while under, while people are under the influence of psychedelics. And I think the gestalt of those data correct me if I'm wrong is that compared to the non -psychedelic state that under psychedelic influence, there is far more, let's just call interconactivity or communication between a brain areas that typically aren't communicating, which is not surprising to people given the subjective effects of these of these drugs.

45:40What is the evidence that after the psychedelic journey is over that some or perhaps all of that enhanced communication across brain areas is maintained? And if so, what role do you feel that could play in these incredible positive therapeutic outcomes? Yeah. So we've had some recent findings in that direction where yes, it's true. And the picture that says a thousand words, some people might be familiar with are these two circles, a project that we did in collaboration with some researchers, where ordinarily the communication is going on within systems. Like other regions of the visual system will be speaking mostly within the visual system, there'll be a kind of clikishness or modularity to the quality of the communication in the brain.

46:40And then the cool finding with Salasibim was the first paper is the communication, yes, it sort of transcends these modules and becomes much more intermodular crossing different modalities. And that effect correlated with the magnitude of the subjective effects and then we replicated it with LSD using different methods. And New Paper will come out soon where D &T showing 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 or global communication in the brain. And this is while under the influence of these drugs.

47:24So putting people into a brain scanner while they are under the influence of the drug. Yes. That itself must be quite an experience given that these scanners are small tubes. You're in a bite bar, you've got a bite bar in your mouth, that's quite a study. You don't always have a bite bar. At least with the psychedelics, but yeah, you've got to keep your heads still and you have the loud MR scanner noise going. But because it's regular, there aren't too many surprises. So it's actually surprisingly tolerable. And you're in a hospital setting, so you're not worried about what would happen if you had a cardiac event.

48:04You've got professionals around and most people generally tolerate that setting quite well, surprisingly well. But yeah, we do all that. And yes, we do see that opening up of the communication across systems in the brain. And it does speak to kind of intuition about the subjective experience that different modalities might be blending with each other. 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 communicated? Yes, so there's a few reasons why some modeling work, the computational modeling work that first identifies whether 2A receptor is and then looks at models, its basic effects on neural activity will recapitulate the or recreate the effect that we see actually in the data with the scanning.

49:09So doing the computational modeling, you can see the same effect by knowing whether the key receptors are and then making them do a certain thing that we know psychedelics do. I can imagine two possibilities, and I think it's important to distinguish between these two. One possibility is that the activation of serotonin 2A receptor leads to increased connectivity and thereby auditorian visual hallucinations emerge, changed patterns of thinking emerge, etc. That's sort of the obvious interpretation, but 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 unconscious hallucinations?

50:04In other words, is it the increased connectivity that's leading to the subjective experience or are those two things happening in parallel? Well, they happen in parallel and they map to each other, but the question of causality, what causes what is the tricky thing where I would suggest that the causality is circular, that they influence each other, and this gets a bit philosophical, but it kind of matters, because otherwise there's a trap that it's easy to fall into where you're thinking that it's all about the brain action causing the subjective experience, and that's typically what we do in cognitive neuroscience.

50:48It's kind of like the sort of first port of call kind of materialist approach, but one can be a materialist, essentially, but still appreciate that circular causality that mind also interacts with brain, and it's so hard to pick the two apart, and there is a kind of essential dualism where subjective experience is the thing in and of itself, but that's not to divorce it from what's going on on the biological level. The reason I ask is because 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 non -psychedelic, it kind of gets lumped in when we get back to that later, but that do not produce hallucinations or massive changes in subjective experience.

51:56Actually, I think this is what initially got us into conversation on Twitter as I had learned about this paper published out of a group at UC Davis that essentially modifying psychedelics so that they have potential therapeutic application for the treatment of depression, but zero hallucinogenic properties. I thought, wow, this is going to be a very controversial thing in the world, because the history of psychedelics, as you pointed out, has been one of people accessing different modes of thinking, feeling, seeing things, letting go, trust, etc., a therapeutic relationship. And here we have, I don't want to say pharma because it's not really pharma, but we have laboratories who are trying to tease apart the activation of receptors, independent of all that subjective experience in order to essentially treat the same conditions.

52:45I'd love for you to comment on this where you think it might be going, and whether or not you think that's the right or the wrong approach, if it has any validity at all. It is pharma, it's just smaller pharma, sort of start -up pharma. Okay, so pharma would like to have drugs that can cure depression, but don't make people hallucinate. Is that called? Oh, they would. And patients might. And the system would love it, because the system is used to it. It's medicine. Right, and it doesn't give this this mental imagery of the summer of love in San Francisco or of kaleidoscopies. It's more, you could imagine the more to be careful with my wording here.

53:29Those who would not be inclined toward that might embrace a therapeutic that is strictly effective at treating depression with no hallucinations. Yeah, and it doesn't look like an individual lying on a sofa, crying their eyes out about the life that they've lived, and that deep catharsis being life transforming. They're very different from that model. I'm skeptical of it. For a few reasons. And one is that I can't see the logic. I can't see the pieces fit in a way that's compelling. And I'm also skeptical because I think it could easily be wishful thinking because of that point patients would like it and the system would like it.

54:28And I just, you got to bear that in mind as well. So wouldn't it be convenient, you know, if it were true, and you could get the therapy to action without the psychedelic effects? Well, in a way, that's a little bit of what micridocing seems to be designed to do. Like you said, take dosages there below that perceptual or awareness of some effect threshold over a longer period of time in an attempt to ping the circuits or twist, you know, alter the circuits, but not hallucinate, not have a catharsis. So if micridocing could do that, and it's subperceptible, the micridocing isn't psychedelic action because where's the psychedelic action?

55:12When 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 new? Okay, maybe it's a bit new and people are now developing direct to a agonist rather than indirect through a serotonin release. I like the selective serotonin reoptic inhibitors, the SSRIs like lexapro, you know. Are there any SSRIs that selectively agonize, which folks, by the way, means activate in a good way, agonist sounds terrible to those non -formed might think that mean that disrupt, but that can activate the serotonin to a receptor.

56:04Are there any drugs that will do that that are not psychedelic? I'm not aware of any, but then again, I'm not a psychopharmacallic. There are. I mean, are there any that are licensed and used as medicines in psychiatry? I actually had this debate recently on social media and I couldn't see, I couldn't see a compelling example. I saw two A agonists that we use for other things. Yeah, a compound like Lisseride used in treating Parkinson's, but actually it's more of a dopamine agonist. And they're always hitting other things, right? Yeah. Yeah. They're tapping other neurochloroetrasil. All there being through other things.

56:43So is there a selective serotonin to a receptor stimulator, an agonist, that it isn't psychedelic, that is therapeutic in psychiatry and the answer firmly is no. I haven't seen it yet. Will they develop one? Well, for patients, say, I hope so because it would be great. Let's wait and see. If they do, I doubt it will be psychedelic and I doubt it would have much to do with psychedelic therapy. And it would be much more like the system we're used to of chronic pharmacotherapy. Take your drug every day. Let's hope they find it and it works for patient's sake. But as things stand right now, I'm a little skeptical.

57:30Now, 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, spine growth, synaptic spine growth. Yeah, by the way, folks, just to I'll interrupt for the data, necessarily spine, the bone, you know, the not the cerebral column, but spines are these little tiny twigs with bulbs on the end of neurons that allow for communication points between neurons. So neuroplasticity is often associated with growth of dendrites and spines and so forth, which is what Robbins referring to.

58:12That reminds me and I just want to make sure that 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. And then I'll just throwing another question there because we're on to 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.

58:48I mean, subject in your experiment, I take do come in in the morning, I do my psychedelic journey five or six hours later, parachuting back to reality as we call it. And then I go home, increase connectivity lasts for how long and how long are the structural brain changes occurring? Well, you're asking fantastic questions 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 to first of all, 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, that increase in global connectivity, functional connectivity.

59:32Do 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 effect similar to what you see acutely 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.

1:00:23And 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. So interesting. Yeah. I mean, just a state of a different way. So what Robyn's referring to is when he say modularity is neuroscientists, we think of the different modular networks of the brain that, the eye talks to a region of the thalamus involved in vision, which talks to the visual cortex, which eventually converges with auditory information, of course.

1:01:10But there's a separation or modularity of function. This increased connectivity is cross -modular during the trip, but afterwards as well. And you're saying that that correlates very strongly with the strength of the therapeutic outcome for depression. I mean, the logical extension of that is that extreme modularity of brain function is depressive in some way. Now, we don't want to go too far, but what does that mean that increasing crosstalk between different modules of the brain is so strongly correlated with positive therapeutic outcome? We don't know other than as a relationship. I mean, this is this is the thing.

1:01:52We 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 mode of brain functioning if you're not getting stuck in modules or the modules aren't excessively cut off from each other. But you see different things with different presentations. If you were to look at cognition, sharper cognition is actually associated with more modularity. So it's a rule that's a little slippery and we need to be careful with it. I just again, I'll forgive me for interesting, but I think I have friends who are, I would say, are on the spectrum who are very linear in their thinking and extremely intelligent in the kind of classic sense of being able ratchet through hard problems to arrive at a solution.

1:02:50And then I have friends who are, let's just call them, they are from the creative communities outside of science that are very expansive. They see connections between many different things, but sometimes you have to, not all of them, 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're not random thought generators. But there's a nonlinearity or randomness to their processing that's distinct from these other folks that I'm describing as on the spectrum.

1:03:27And of course, it's a spectrum. There's a whole range in between. It sounds to me like there's some therapeutic value to being able to move along this continuum from the more linear to the nonlinear. Is that is that correct? Well, I think so. Yeah, it's resonating what you're saying. It's speaking to my intuition that, you could be very passy, passing things up, chopping things up like an analytical scientist. A splitter. A splitter, as we say inside. You're either a limper or a splitter. Or the way I'm being very particular about what went to call something psychedelic, that kind of passy analytical way of thinking you might associate with a more modular system.

1:04:14Whereas the system that's more globally interconnected and open might be more flexible and creative and divergent in the associations and so on. So yes, that's speaking to my intuition to how 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, which is a whole physical depression, that it's easy to fall into and if you do, it's hard to get out of. So almost if I understand what you're saying correctly, almost like getting stuck at what location on this continuum, because most people don't reside at one extreme or the other full time and kind of migrate back and forth between expansive states and more linear states.

1:05:06Like you do with low mood, if you're healthy and inverted commas, you can feel your low mood, your disappointment, but you can spring back. But someone with you. You know you can spring back. Right. Residus suicidal depressive person or to a cytolid depressed person. Somehow, at least in my understanding, there's something about the extreme depressive states and extreme anxiety states, something my laboratory is a bit more familiar with anxiety, which alters the perception of time such that people feel like that negative state is going to go on forever or that if it goes away, that it's going to return at random.

1:05:51Kind of a vulnerability to the time domain. Yeah. Yeah, that's it. It's so tragic, but that cognitive bias in depression, that everything's hopeless and that there is no light at the end of the tunnel. Yeah, so if you were to get stuck in that rut and have that bias, then you're cut off from other things, other sensory modalities or modules, you know, cut off from the world, cut off from other people, stuck in your inner rut. And so yes, I think we're sharing this intuition that a decrease in modularity or an opening up of the system, the brain, could relate to an opening up of the mind that is kind of enduring after the psychedelic dosing session.

1:06:41And yeah, and the third replication was to see in healthys an improvement in well -being because that healthy, we don't look at depression. So these are people that are healthy walking into the trial, take psilocybin twice. Well, actually they do, but the first dose is 1 milligram, which they don't feel, it's a placebo dose. What a quote, micro. Yeah, we sticky G on the heads to measure their brain waves during each dose and 1 milligram, you see no change. So we, I think that you microdose or so, I'm just kidding that. I think again, the microdose has always just been a little bit skeptical based on my conversations with the scientists actually doing the work with psychedelics, it seems like the answer keeps coming back.

1:07:29Do one or two, maybe three macro doses in a controlled safe setting? Well, that's compelling. The evidence for that is compelling and that's what's making all the difference right now. And microdosing is just appealing, but again, you know, science isn't about what we want to believe. It's about what's actually coming through and what seems to hold up, you know, to testing. Would you say that's right? The one or two or three sessions and how far apart are those typically spaced in time? Typically, one, two, three weeks across the sites is the way people are doing the psychedelic therapy dosing sessions, two sessions, you know, Hopkins Imperial NYU.

1:08:20That's been a kind of default to we actually used three in a current anorexia trial, psilocybin therapy for anorexia. Two patients left to see after 19 who've gone through the trial. Very exciting results there. You're seeing a alleviation of the obsessive thought about food and willingness to consume healthier amounts of food. Yeah, even improved weight the long follow up. So so critical. I went we didn't episode on eating disorders and I learned that anorexia and arosa, 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 etc.

1:09:06But anorexia and arosa being the most deadly of all psychiatric illnesses, which is a big statement because, you know, manic depression, so -called bipolar depression, has a 20 to 30 times the typical suicide rate. Basically, many anorexia people with anorexia, I think is how it's now. Is what one says, not anorexics, but people with anorexia often die. Many of them die. 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 so strong. And so it's so rewarding to be doing that trial and to be seeing good results.

1:09:53I have to check myself a little bit that I'm reporting on it in this really promissory way. And the trial isn't yet publicly released and published, so it's still ongoing as well. But that was three sessions. It is three sessions and I can't say what the dosage is because we still have there is a blinding component. But there are three dosing sessions in there. Let's see now, I think there are two weeks apart. And we do the follow -up. Yes. I'd like to close out this description of the of the journey and the trip by extending past the day when people actually take the drug into this. What I've heard described is the integration phase.

1:10:42You know, you have to reintegrate, right? 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 are these patients or subjects and studies having daily conversation with their therapist? Are they journaling every day? And 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. We're people to use psychedelics. 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?

1:11:32In other words, how long does this so -called integration last? And you know, how far can we take this? I mean, I could imagine that how often one chooses to think about the insights could also have an impact. Because clearly people went to raves. Clearly people did psychedelics in the 60s. We don't know if 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 again, are incredibly impressive. In upwards of, as I understand it, 60 % or more people getting relief from depression.

1:12:13Yeah, 70 % incredible, especially when compared to the typical anti -depressant treatments and so on. So, what is this business of integration? How is it done properly? Yeah, yeah. Gosh, well, how long does it last as well? A lifetime. You know, life is a journey. Like a trip is a journey. And there's always work to do. And I was Jack Cornfield says after the ecstasy, the laundry. I love that. Yeah. There will be other good ones as well. I'll be very happy to forget them. But yeah, so the work's ongoing and there, yeah. But this gives you a foot up. It enables people to do the work more easily.

1:13:06And that's true. The classic psychedelics is also very true of MDMA therapy 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. So, it's such an essential component of the treatment model. But one has to be realistic as well. You know, by saying our integration lasts a lifetime, well, people delivering a service can't be there for a lifetime. So, what's the answer there? And people are wrestling with that issue right now. And I think one of the solutions might be that it's in a sense on you to a point, you know, the therapeutic team can treat you to a point.

1:14:03And 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 that's the way it is. Or you have a, another psychedelic treatment. 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 I'm using meditation intentionally here, because they actually think that meditative practice, spiritual practice, elements of spiritual practice, could be a very important complement to psychedelic therapy.

1:14:53And I think it's probably doing something similar in terms of promoting an ability to sit with. A former colleague of mine said it quite well in relation to psychedelic therapy versus chronic pharmacotherapy or like SSRI being on them all the time. So, psychedelic therapy allows you to sit with rather than sit on. And I thought that's quite good. Yeah, so, you know, the meditation, the mindfulness, the ability to yes, be present -centred, but also present -centred and accepting. So, if things come up, you can watch and process and then let go. That holy grail of mindfulness, you know, awareness without reactivity responds.

1:15:47I grew up in the Bay Area and you'd hear this language, right? And I'm not being disparaging this. I have friends that are on the board of Esselin 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, greats on me, which probably just means I have issues. But, then surely I do. But, you know, it is like, what does that mean, right? It's sort of saying like, go to be the observer but not be drawn into the experience, you know, and again, I don't want to be overly reductionist, but what I find so compelling about the emerging data, is it really data on psychedelics as treatments for depression and trauma, namely, psilocybin and MDMA, is that it really seems to allow people this space that is so commonly thrown around, you know, giving space between stimulus and reaction.

1:16:41I mean, Victor Frankl talked about this, but, you know, I've been reading a wonderful book called The Prince of Medicine, good dates back to the origins of medicine, very dense book. People have been talking about this stuff and thinking about this for thousands of years. Psychedelics seem to give people access to that better version of self, which is remarkable. What's also remarkable, perhaps worth pointing out, is that five years ago, I never would have been comfortable having this conversation. I would have 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.

1:17:22Speaking of which, I know you're doing a trial on first time use of psychedelics. What inspired that and what are you observing? And as you tell us that, please give us a few of the key contours. What's the dose? How old are these subjects? I'm assuming it's men, women, are they suffering from depression or not? What's the landscape of that study? I realized this is still early days of the study, or maybe it's close to completion. It's not yet published, however, correct? It's not published, it's not submitted, it is completed. This was another one of our COVID studies, in a sense, meaning COVID hit and we had to finish the study, and it was hard to finish the study because of COVID.

1:18:06That was true about psilocybin therapy versus esitalopram, lexapro trial, which is published in New England Journal of Medicine. That paper, by the way, folks will provide a link to in the show note captions, as well as some of Robyn's other papers. I think that 2022 New England Journal paper is really fabulous given the different dosages and comparison to essentially what is micro dosing and the comparison to sytali -pray. That's interesting that you link the way we gave small doses of psilocybin to micro dosing. We didn't think of it that way. We thought it was just a necessary placebo for the big dose, the 25 milligrams, so that we could say to everyone we're giving you psilocybin and not be lying.

1:18:56For those who got esitalopram, lexapro for six weeks, they got a very, very low dose of psilocybin, but it allowed us to standardize all the psychotherapy and so on. But the other study that you're referring to was in healthies, healthy volunteers, middle aged average age, I think it was 40, so not your typical student study that is so often the case in psychology research, all the undercrets and volunteering for your study. This is more of an age range and also I think it was an unique proportion of male and female. All the staff actually were female, which the staff were very proud of. Although it produces its own potential confound, right?

1:19:42To have all one sex of staff. Possibly. Yeah. They did a good job in the sense that 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 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 the plan is to give them their first ever psychedelic experience.

1:20:26So 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. Again, we gave them a placebo dose of psilocybin, one milligram. We stick EEG headsets on during the experience to record the brain activity from the scalp, the oscillating electrical activity. And we do the MRI scanning 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.

1:21:12So 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 formerly quite 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.

1:22:03So the bigger the trip, the bigger this entropic brain effect, now pretty well replicated finding. But then the MRI, 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 tracks. And we saw a change in major tracks. So we sort of limited our search space to really thick tracks, really thick fibers. And the fibers that came through as changing were ones that traveled between the prefrontal cortex and the thalamus and the striatum.

1:22:57There were two tracks, two prefrontal tracks that changed. And they changed in the direction of a decrease in axial diffusivity, which could be interpreted as tracked integrity, where a decrease would be an increase in tract integrity. It is something that you see in the developing brain that axial diffusivity decreases as a brain goes from being a baby to being an adult axial diffusivity goes down. And then in aging and pathologies of aging axial diffusivity goes up. So 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.

1:23:44If I understand correctly, and I'm perfectly happy to be wrong, by the way, that this decrease in axial diffusivity is translates to a higher fidelity of communication between the prefrontal cortex and the thalamus and striatum as opposed to less. And your description of this is somewhat like the the transition from babyhood and childhood to adulthood speaks to the same where we know that there's a massive calling 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.

1:24:22Is that right? Ish because the change was anatomical and not functional. So the other stuff is is really measuring communication in in the brain by looking at how the activity fluctuates across time and whether those fluctuations in activity, a synchronous between regions. And if they are, we say they're functionally connected and we infer that they're talking to each other because they go up and down in synchrony. But when it comes to the anatomy, we're talking about the just static material stuff. And so we're seeing the fibers in a property of the fibers change. At least that's what we think.

1:25:11And recently we had an independent person come in and reanalyze the data because one of those things, incredible finding requires incredible evidence, really strong evidence. And I would say the evidence at the moment is one study. So we need to be cautious on that. But we did reanalyze it and use this correction procedure free water correction to be more sure that it was a change in in the actual microstructure rather than something to do with the extracellular space, the water surrounding the fibers. And it came through. In fact, the change was strengthened by doing this correction step. So these are, this is neuroplasticity as the consequence of one first time session with 25 milligrams of psilocybin.

1:26:04Yeah. Yeah. So we're excited. And the two different, you know, the second analyst coming in wasn't sure she believed it. And then she, you know, thought this correction technique might kind of kill the result. And then it came through. And she's like, OK, now I'm excited too. So we'll see. We don't know what it means. What does it mean functionally? We don't know. How did the people change? Well, psychologically, as I said, well, being improved, we did look at their cognition. And we used a cognitive flexibility paradigm that looks at people's ability to notice a rule change and then flexibly adapt their behavior based on noticing this rule change.

1:26:48And people improved after the 25 milligrams and didn't significantly improve after the placebo dose. There weren't correlations with the the DTI change, the cabling change and these psychological outcomes. But, you know, with these studies in smaller sample sizes, you don't always see those correlations come through. So it's something we don't know what it means, but it's a change in brain anatomy that's in the opposite direction to what you see in an aging brain or with pathology of aging. And it's what you see in a healthy brain as it goes from, you know, normal, neurodevelopment into adulthood.

1:27:31Very, very exciting and intriguing. And I appreciate that you highlighted that it's just one study, although from everything you said, it sounds like it's been done with immense rigor. So we will eagerly await the publication of that study and so we can peruse all the data and the subsequent studies. 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. I mean, treat bifibromyalgia because I have a good friend who also I won't reveal who it is. And no, it's not me. This isn't I have a friend who also is a scientist who's sits at a fairly high position in the National Institutes of Health who quietly has expressed to me that they are incredibly frustrated with the fact that the standard medical community has largely ignored fibromyalgia.

1:28:25And that for many years, it was kind of lumped with things like chronic fatigue syndrome and other so -called again, so -called I'm not saying this, but people offer them for these as oh, it's psychosomatic. That's all in your head, which as a neuroscientist 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 the world is starting to appreciate that more. But first of all, maybe you could tell people what fibromyalgia is, what inspired you to do a study on fibromyalgia using psilocybin of all things?

1:29:00Because that's surprising to me. And if you are allowed to or if you have access to the data in mind, share with us a little bit about what you're discovering in that study. 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, chronic lower back pain. This is more generalized. And for that reason, it's hard to sort of know what it is. And that's why it's been a controversial space in medicine.

1:29:46And it's been, yeah, it's had that charge thrown at it that maybe it's psychosomatic and just to your point is anything ever independent of the mind anyway. But this is actually a fascinating space for how subjective experience, the lived experience and the mind can influence the body. Because there's some really interesting literature around the etiology, 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 a background of trauma and how that can relate to issues related to inflammation and how that can express into things like fibromyalgia syndrome.

1:30:47I just said, be very careful there because if you go in with an assumption that there's some very 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 going to uncover very trauma in every case. Now the team have treated I think eight people and it's going it is going very well again. I just want to be careful with how I describe it to manage expectations and not get too carried away. But I check in with the team every week and they're still based in London doing the work.

1:31:32And 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 EG cap on in the sessions like in the Healthy Volunteer Study, but this time now taking into a clinical population. And so they're in the I'm they're they are wearing an I mask under the influence of 25 milligrams of psilocybin. Most of them probably have not done psilocybin before. So it's a little bit like the first time study in some sense. They have fibromyalgia that's debilitating in some way. They don't they don't want they don't want it obviously.

1:32:23And during the session, are they thinking about their pain? Are they being told to think about their pain? They're not being told to think about the pain. In fact, as I understand it, while there is a therapeutic model around acceptance of the pain, it isn't unlike some of the PTSD work you aren't encouraging them to focus on you know, the index trauma and then you know, work through it and try and digest it. We don't do that with the pain. So the pain's there, but there isn't an invitation to focus on it. And that's probably one of the differences with classic psychedelic therapy versus MDMA therapy.

1:33:05Arguably, MDMA therapy is more like a bit closer to traditional talk therapy, but there is more dialogue. People are able to talk on MDMA. In the MDMA trials, do you know whether or not they used eye masks or because this seems to be an important distinction between as you describe the therapeutic trip versus the trip that one does going into the woods and taking you know, take a cell in the woods or at a party or while staring at a poster or a leaf. Again, I'm not trying to trivialize those experiences. I mean, obviously they can be profound, but so I'm told. But the MDMA trials seem to involve, as you said, more directed dialogue and sometimes even kind of empathic connection between people by their actually looking at one another, you know, the eyes and eye contact being such a key part of the human social cognitive connective networks.

1:34:15So do you know if they put eye masks on people during the third or people? I'm pretty sure that they have the eye masks there. Right. Because a lot of the MDMA work and I was part of an MDMA trial. It was as I understand gear toward developing because it's an empathogen empathy toward the self. Yeah. I'm pretty sure they have the eye masks there, but they probably, and it's a great question because you can formally test this. It probably don't use them as much. The thing is with the classic psychedelics, if you're looking at your guides, your facilitators and their faces are melting. I know. You know, an MDMA, you just might really start to feel more connected.

1:34:57Yeah, especially beautiful. And you know? Sure. And yeah, there's that fascinating effect of loving, you know, the people that you're with. And so, yeah, I imagine they talk more and use the eye shades less. And it is more interpersonal, rather than like intra -personal going inside. They do use a fascinating terminology that some people have critiqued, but it is a very interesting phenomenon and it's this notion of the inner healer. They use that language a lot. It's been critiqued because it sounds very suggestive, you know, and that's probably one of the vehicles here driving the therapeutic process is suggestion.

1:35:41I think we have to be honest about that. But so when they go inside, that's another term that we use very much in the classic psychedelic therapy work, you go inside, you know, you put the eye shades on and people are encouraged to go inside, you know? But when they do that in the MDMA work, especially, they might be told explicitly and listen to the inner healer, you know, and that kind of language. So you could see how a cynic or a skeptic could come in and see that as some kind of like suggestive priming or biasing. I think they have points. Skeptics often do, but I don't think it is all of the story.

1:36:27And just briefly, because it's an interesting point, speaking to that point a bit, in our cello -sybin therapy versus S -tallopran trial, we measured pre -trial expectancy and we did it for both conditions. So, you know, what kind of improvement do you expect with the lexapro, the S -tallopran at the end of the trial, and what kind of improvement if you go into the cello -sybin arm and get a big two big doses of cello -sybin? What kind of improvement do you think you'll see in that? And of course, it was a coin flip as to what arm people went into and there was no crossover. And what we found was that it was true that we had a sample bias.

1:37:14So most people had higher expectations on average. There were higher expectations for cello -sybin and its efficacy or effectiveness versus the S -s -s -r -i, the lexapro. However, when we looked at the correlation or the predictive relationship between pre -trial expectancy and response, we saw that pre -trial expectancy for the S -tallopran predicted response to S -tallopran across virtually every single measure, all these different measures of depression and anxiety and well -being. And I think none of the scales, I'm pretty sure it was none of about 12 or so mental health rating scales, was there a relationship between pre -trial expectancy?

1:38:02Even though it was high, it didn't predict, pre -trial expectancy, didn't predict response to the S -s -s -s -i -bin therapy. So that was a bit of a, you know, smash on the head for the idea that the classic psychedelic therapy is some kind of placebo response. And I think it's so important to address that question because if it doesn't come through as it didn't come through, then it opens up even more intrigue about, well, what is it then? If it's not just a placebo response or a super -pulcebo response, like an amplification of the placebo response, then it must be something else. And how intriguing it has a direct therapeutic action, it must be something.

1:38:52And we don't yet know what it is. I talked about the residual, you know, increase in global connectivity. That's one possibility. But the truth is we're just scratching the surface. And yet that therapeutic outcomes are again just so marvelously impressive. I'm curious as to why, as well, there are that many labs, but the laboratories that are focused on classic psychedelics for the treatment of depression. And now, as you mentioned, promising results for anorexia and fibromyalgia as well, although preliminary, very promising. Why the lack of attention toward LSD? Is it that the LSD trips are just too long?

1:39:37Is it that they are qualitatively different? Are there any data on non -microdosis of LSD? And here I want to be very careful because I learned through my interactions on social media that this term microdosis is very misleading. And in some cases can be dangerously misleading because, as you mentioned earlier, the effective psychedelic dose or the effective meaning that can induce a real trip with hallucinations, etc. Of LSD is actually in the microgram range. So some people hear microdose and they think microgram of LSD is a micrograms is a microdose when, in fact, a macrodose of LSD can be measured in micrograms.

1:40:25So this is where, in the absence of scientific training, people can really go astray. Or even in lack of understanding of the metric system. And since now you're a recent rival to the US, fortunate for us, sorry, England's loss is the US's gain by Robbins' move from England to the United States recently. So score one for us. But why isn't there more use of LSD in these trials? I think it probably is the duration of the trip. It used to be stigma. And it was easier to get your psilocybin study through because others were, they were getting that through.

1:41:14So there was a lot of work coming along in doing the psilocybin work at Hopkins. So you could appeal to that president and say, well, they're doing it over there, you know, can we not do it in little England? So that's how it worked for us. We did actually go on and do an LSD study once we kind of laid the foundations for doing this kind of work. And it was a brain imaging study. It was a really extensive one actually where we use both MRI and another modality called MEG, sort of super EG in the sense. But, you know, why didn't we, why didn't that turn our heads to think, oh, should we not be doing our trials with LSD?

1:41:59It does have something to do with a pragmatics, like a study day with psilocybin is long enough. So four to six hour trip. Yeah. And the FDA asked us to have the people in the lab until eight hours post dose, with personally, I think, could be quite excessive, especially if it's a low dose. And, you know, if you have that in the placebo condition as well, it becomes a long day. In practical. Yeah. Scientists are not paid nearly enough to warrant the, there's no such thing as overtime in for the graduate students and postdocs. Yeah. And it's often that there's, you know, more junior members that are doing that really hard work.

1:42:41It was described very well to me by a student when I was a graduate student said to me, they really can't afford to pay us by the hour. Because we used to work. He was an electrophysiologist, so he would run experiments. No joke, folks. Three to five day experiments, sleeping in bouts of two hours here or there in a dark room with a bunch of equipment and recordings. So these are long, long acute physiological, physiological, electrophysiological recordings. So, yeah, no, no scientists does it for the money. I promise you that there is money in pharma. There is not money in personal income. It's not lucrative for the basic scientist.

1:43:24So, yeah, LSD is what anywhere from eight to 15 hours? Yeah, 15 would be a little long. You'd be a bit worried if you were still tripping at that time. Maybe with a really big text. No, just kidding. But yeah, eight hours plus and dose dependent. Yeah, if it's a bigger dose, it's a longer experience. But, you know, if you're going to dose, let's say, you know, 10 a .m. in the morning, which is more or less how it often goes, then that's six p .m. still feeling the effects. And then how long do you wait now to kind of close things out before they can go home? Even with psilocybin, yeah, people still work into the evening.

1:44:07And the staff are always there later, of course, because they've got to pack up. And yeah, so these are long days. And it's just, it's too much, you know? That makes sense. You know, practicals and constraints. I learned from a recent guest on this podcast that we recorded with Dr. Sachin Pando, who was a colleague of mine when I was down at the Salt Institute, is a pioneer to a lot of the studies on so -called intermittent fasting. That the reason the intermittent fat, that the eating period and these studies in animals and now on humans is eight hours. The sort of feeding window in these studies is because the graduate student was going to otherwise lose their relationship because there's significant other says, listen, you can be in the lab for 12 hours.

1:44:50That meant some hours before the experiment, then eight hours and then some hours afterwards, but you can't stay in there longer. And many people use the eight hour feeding window as a consequence. So the science has to exist and be carried out in real world frame. It does. It does. MTMA is a little bit, a little bit shorter, right? It's about a four to, it's also about four to six hours. Yeah, it's kind of similar to psilocybin. Yeah, it is. And actually in the maps work, they reduce after a certain point. So the boost, the boost, they have a boost. They're optional booster. Yeah. So, so there is that.

1:45:23And now people are thinking, well, even these psilocybin sessions are long and expensive. And if you have to have two staff members there all the time, that's expensive. That's where most of the expense is, is in the staffing. So can we abridge the experience, make it shorter and get away with this? And get, get similar kind of therapies outcome. So there's a lot of interest in that direction. May ask about, I'm sorry to interrupt, but I want to make sure I don't forget to ask about combination psilocybin MDMA therapies. The reason I ask about this is, and here truly not me, but I know people who do self -administered combination psilocybin and MDMA.

1:46:10I think I have this right. I think it's called a hippie flip. There's another one that involves LSD too. Again, I'm not suggesting people do these kind of drug combinations. But the way it was described to me was that the psilocybin, because it's so serotonergic, sometimes can be not a downer, but can have a bit of a kind of a murky feel to it. Some really deep introspection, sometimes in the darker realms of ones, psiky, depressive thoughts, etc. Not that it necessarily stays that way throughout the trip. But that the MDMA, because it has a very strongly serotonergic, but also dopamineergic, I mean, so it has an emphetamine component, a cocaine -like, in fact.

1:46:52If you've ever seen someone on an MDMA, their pupils are about the size of quarters. For a reason, they're in extremely extreme autonomic arousal compared to a sedative, which by the way, would constrict the pupils. So they describe the use of MDMA to kind of balance out the kind of affect component of it. What are your thoughts on combination psilocybin and MDMA? Does this hold any therapeutic potential? This is obviously a backyard chemistry in the sense that people are, or, you know, kind of cowboying this stuff on their own, which again, I don't really recommend. I like to see the science go first, but I understand this is how it works in the real world.

1:47:35Yeah, what are your thoughts on combining compounds? Yeah, well, I guess they're cowboying it in recreational contexts, but also underground therapists do work with this combo. That's what I'm referring to. So I'm not talking about people parting with this stuff. I'm talking about there are thousands now of therapists that offer psychedelic therapies illegally, really, because it's not legally, not in the US, to possess or sell, but that are doing this. So that's really why I'm asking. Yeah, and, you know, I think there's something to be said for when I have to be careful with this as a scientist, but, you know, if they're doing it, are they using some kind of trial and error?

1:48:14The same is true, of course, with the, you know, longer history of psychedelic plant medicine use, if by plants, we include the fungi as well, so in the extended sense plants, you know, there will have been trial and error there. It might not be as systematic as the science we do today, but maybe there's been a learning process and maybe what they do, they've come to because they found it works. So by that principle, I'm interested in that combination and whether it does offer some advantages, maybe in certain patients, you know, one of the buzz terms in medicine these days is precision medicine, a precision medicine and personalized medicine.

1:48:58So maybe there are certain cases where, you know, introducing, say, Solaceibin after the MDMA or the other way around could offer some advantages. And the differences are interesting, you know, Solaceibin can get you to deep places, maybe, you know, the kernel of your suffering and major life experiences and complexes that are causally linked to whatever the pathology that you're presenting with. But it can do it sometimes quite aggressively, you know, and if it's, say, post -traumatic stress disorder, it can be overwhelming and you can fight it. And really it's that it's that, you know, the resistance is really challenged and they fight back.

1:49:52And the therapeutic breakthrough and the progress isn't happening because you've agitated the defense mechanisms, whereas what MDMA offers is something arguably more directionally reliable in terms of, in terms of the valence, like it's more directionally positive generally an MDMA experience. Hard to have a bad time on MDMA. Yeah. To be quite blunt. I mean, one of the concerns I had with MDMA, I've never done it recreation. I have had not and have not ever done it recreationally. But when it was done in this therapeutic setting, I realized because there was music on at the beginning, I actually asked them to turn it off because I realized that the music was becoming such an attractor to my attention that I suddenly was starting to think about music and my love of music, which was not the focus of the session that I was there for.

1:50:48And I'm glad that they did turn the music off because the moment they did, I was able to drop in within the I'm asked to this to sort of go inward and address some certain issues that at least to me felt key and productive. So that seems to be the kind of hazard with MDMA is that it's such an empathogen that one could start to, you could go down any number of different rabbit holes. Yeah. But it's also, it's a strength because you, well, the classics like Solaceibing can take you there very reliably but maybe a bit aggressively, MDMA makes it easier to go there. And that's its strength. And that's why that marriage of MDMA therapy for PTSD in particular is a good combo.

1:51:35It works because you are going to go there in a sense you have to really make the therapeutic progress. You're going to have to go back there. But we're going to set it up so that you can go back there and feel safer and more trusting and be able to go back there. Whereas you've never otherwise been able to go back there without dissociating or having horrible flashbacks and so on. So that's the strength that it offers. I guess the limitation would be that maybe it doesn't take you as deep as the classic psychedelics. And I tend to think I'm biased on this one that there's a kind of honesty to the classics in that it is, it is hell as well as heaven, you know, and that's the psyche.

1:52:24It isn't all roses. I really appreciate that you bring that up because I think that there's such a fear of so -called bad trips. There's such a fear in non -psyched states to avoid the painful. And everything, everything we know from trauma and the treatment of trauma. We've had several guests on here. My close colleague, close, close colleague at Stanford, Dr. David Spiegel, associate chair of psychiatry, clinical hypnotist, amazing, amazing human being and scientist and clinician. As really just, you know, like embedded this in my mind that the only way to deal with trauma is to get right up next to that trauma to the point where some relief is experienced.

1:53:10There is no other real way. And so I really appreciate that you're saying that the classic psychedelics may offer the, with a very strong nudge, perhaps, the opportunity to get into the uncomfortable in a way that MDMA or some non -classical psychedelics perhaps do not. We're talking about time frames or duration of trips and these different compounds and how they defer and how they're similar. I'd love for you to educate me on DMT and some of the work that you're doing with DMT. My understanding is that it's a very brief trip, minutes. People I know who have done this, again, therapeutically.

1:53:51Actually, I'll just point to one very exciting, I think, group and initiative, which is the Veteran Solutions Initiative, which is a group, this is carried out in Mexico, but in conjunction with laboratories at Stanford and elsewhere who are evaluating the neural changes. And this involves IBegin, which is EboGo, which is a very long duration psychedelic, 22 hours or more, followed by a, I think, one or two doses of DMT. This is for veterans to deal with any number of issues. It appears to be working with great success, and I've spoken to several people who've gone through this. And the way that they described DMT, almost across the board was quote, here I'm just pulling quotes, right, anecdata.

1:54:36The most profound experience of my entire life, even greater than the birth of my children, quote, like being attached to the shockwave of an atom bomb, quote, there's no way I would do another dose because the first one was so unbelievable. Interesting, by the way, I think most of us including me would think why wouldn't you want to do it again, then? But this idea that that was just beyond anything. So these are significant, excuse me, these are significant statements coming from individuals who have existed at the extremes of human experience to begin with, right? These are so -called tier one operators within the special operations who exit and may or may not have trauma.

1:55:18But DMT sounds like a big deal. Short duration, really big deal. What do we know about its chemistry? What do we know about how its impacting brain networks? And what in the world is going on that people are describing it as the ways I just mentioned a few moments ago? Yes, it's a rocket ship. If the Salah Sybin is like a ship leaving port, then yeah, this is a rocket ship into craziness. Is it serotonin 2A? It is, yeah, so it is a classic psychedelic. It's a direct agonist, a direct stimulator of the serotonin 2A receptor. It's an order of magnitude less potent than Salah Sybin, but potenties are a funny thing because it's dose dependent.

1:56:13So that doesn't mean that the experience with DMT is less than that of Salah Sybin. It's just that you give more of the drug. But it has, let's match by its stickiness for the serotonin 2A receptor, which is this kind of golden rule in psychedelic sciences that it was discovered in the mid 1980s, this tight relationship between the affinity or the stickiness or the binding potential of a psychedelic for the 2A receptor in particular, serotonin 2A, and its potency and the stickier the drug and more potent. LSD really sticky, very, very potent. You only need those tiny microgram doses. So DMT by its affinity is a little less potent, but by its effects when you give a standard dose, it's just wild.

1:57:05And DMT, because there's another compound called 5 -methodoxy DMT, which is a bit different pharmacologically and subjectively. It's similar in terms of its kinetics. It's another rocket ship. Both compounds in the wild, so to speak, are smoked often. DMT and 5 -MEO people are vaping both actually now. There are vapes that have been developed for people to administer this, but more traditionally it's been a smoking thing. LSD this is clinically not recreationally, or both. LSD both now. I mean, you know, underground practitioners are using the vape pens. They like them because people titrate the dosage.

1:57:56They get a feel for what it is to be going into this state, so that they feel they can let go and go into it. But actually, I think some of the veterans might be giving 5 -MEO after the eye began. Phenomenologically, if there's a difference between DMT and 5 -MEO, people might put it on 5 -MEO being more of a reliable ego dissolution experience, less visual and more kind of all -round immersion in the greater whole loss of self identity and just emotion and everything. LSD yeah, maybe we could just talk about ego dissolution for a second. LSD it's such a sticky, interesting idea. I can take a step back as a neuroscientist and say, okay, ego dissolution, this idea that the, you know, from a very early age, we have a concept of self and that, you know, I wake up every morning and I know I'm me and not somebody else and presumably you do the same and most people do the same, I would hope.

1:59:01But that and that there are objects in the world and people in the world beyond us. But every time I hear about ego dissolution, it sounds like it's a kind of a temporary elimination of the idea that things stop and start and stop between us and everything else. Almost like, you know, in a kind of a, here I'm not trying to sound philosophical or metaphysical, but there's sort of the molecular continuity of life, right? Or all that. It's just little bits. LSD which is true, right? Not a functional way to go through the day, right? Because you want to make a cup of coffee, you don't really want to get lost in that if your goal is to make a cup of coffee.

1:59:43But, but you know, what is the power of ego dissolution? Is it the idea that we, that we belong? Is it a sense of meaning? Is it the sense that we're not as important as we think, which of course could be a wonderfully useful way to go through life, you know, to think that we're not as, and as in like we are vitally important, but we're not the only thing, right? Because I do believe connection is vital as most people do. What is ego dissolution? And why would this serotonin -2 -A activation cause that? That's remarkable. Yeah. Great questions. I mean, what is it? You alluded to it with the start stop, I think, you know, because you could define it by boundaries in a sense.

2:00:35What isn't me is as valid here as, you know, a developing sense of what is me that a child develops at whatever age.

2:00:49And so a major characteristic of the ego dissolution experience rather than just a negative, a thing going away, my sense of self going away, is the positive, oh, now I feel interconnected with other people in the world at large and I realise, you know, that there is that molecular continuity and actually that's a ground truth. And, oh, maybe the ego thing is somewhat illusory or at least the construction of my mind. And indeed it is, right? Well, it is. Yeah, I mean, there's no transcendentalism about that. It's just like logic. I think about it a little bit like family, I mean, we all know what immediate family is, but you know, sort of like, forgive me for interrupting myself, I do it all the time anyway.

2:01:39When I teach neuroanademy, you know, some clever student always figures out, okay, well, that's connected to that and that's connected, but ultimately everything in the brain is connected to everything else. There's just no way around that. That's a true statement. And so you really just have to decide where you draw the boundaries between what are the modules? What are the modules? You could say the brain is just one big macro module. And then you also want to include the body. And now fortunately, people are starting to embrace this idea that it's not mind body. It's both because the nervous system extends through both, of course.

2:02:13So as the same could be said, a family like we're related, right? Not just by virtue of the fact that we're human beings. If we did our genealogical charts, we would find a convergence at some point. And of course, you know, this becomes a bit of a game, but then one realizes that where you draw the boundaries, and if you draw them at brother, sister, parents, biological parents, etc., that's a game too. And so it is just a construct. Yeah, I mean, it is a fun game, you know, where do you draw the line and when to pass and when to collapse? It's also a classic consideration in science, when to pass.

2:02:53The lumber versus the splitter. Yeah. But you ask this question, well, why do psychedelics do it? And there we think psychedelics do it because the target receptors, at least, you know, classic psychedelics do it. And that's important to stress. So MDMA doesn't really do it in the same way. Might soften the ego a bit, but yeah, that's debatable. My experience with MDMA is that it's such a strong in pathogen. Yeah. And that it can and to cause empathy for others. Yeah. Certainly you could imagine situations where one in MDMA journey and afterwards says, you know, oh, these, these my oppressors, you know, are the people that harm to me, they, and here I'm not referring to my experience, but you know, they did the best with what they have actually have empathy for them forgiveness, but also for oneself.

2:03:48That there's an empathy for self. I know I said this earlier, that is very hard for most people to access, perhaps it's not the narcissist out there listening. They'll be like, of course, empathy for self, but everyone else, I think, all the other healthy people or the healthy people, other than narcissists and not picking on narcissists, I have to imagine they suffer too. In fact, I think that's the root of their narcissism. That empathy for self is not something that comes reflexively for most people. And here I'm not talking about self love or self respect, but this notion of being able to see the self as not just deserving of love and care, but actually holding that in place while in confrontation with something challenging in a way that allows more, not less access to adaptive responses to that challenge.

2:04:40I think that's the way I kind of conceptualize it. Yeah, yeah. But I mean, drugs offer a great, they offer great, they are great scientific tools for tackling this question. What is ego dissolution and why do drugs modulate it? And what does that tell you about the brain? Because other drugs like cocaine, releasing more of a different neurotransmitter dopamine, more than serotonin, the opposite is the case with MDMA, is more of an ego inflator. Oh, absolutely. People become hyper linear, hyperlinked to their own desires and wishes and future outcomes become an obsession. It's the stuff of kind of American psycho and the kind of cliches and stereotypes of the 80s cocaine culture.

2:05:30Yeah, yeah. We did a study once actually looking at dose dependent relationship with ego inflation on one axis, an ego dissolution on the other and saw that it just massively passed or differentiated between cocaine and psychedelics. It's quite a neat study. So cocaine makes people's egos super inflated. Yeah, it doesn't touch dissolution and the opposite is the case with psychedelics. At least in your image, to explain how cocaine does that? That would be a great study. Yeah, great idea. We should do that. I have a sabbatical coming up. I've got 12 months of sabbatical coming up. Yeah, I don't want to get, I'm going to show up in your lab.

2:06:11Yeah, that's a really good one. It's right to finish the thread on why psychedelics and ego dissolution. We do know some things or we have some hypotheses and it's that the target receptor is a serotonin to a receptor, the classic psychedelics hit. I heavily expressed in what these days I like to call recent brain because evolutionarily it's recent brain. It's cortex that humans have more than any other species. If you look at a mapping of cortical expansion from say macaque or chimp to human, it's the very same map that you'll find the two -a receptors in. That's the target. It's just easy to think that, oh, well, that could be the egoic brain.

2:06:57The classic psychedelics come in. They scramble up the activity. That's the entropic brain action. In terms of the start, stop, the boundaries, that entropic action spreads out the system. It doesn't shut it off. It spreads it out. Disolution. Yeah. You were talking about the head space as well. So that fits if it's more capacious, it sort of fits. The big qualifier with psychedelic therapy that people rightly bring up is it doesn't last. That's the paradox of it. The paradox of ego dissolution. The ego might go away during the trip and you have these profound insights about the molecular continuity and how we're all one and to connected.

2:07:55Then you calm down. However, long later, the ego comes back, but maybe with a vengeance. Sadly, things can go right when people haven't done the work, perhaps haven't done the integration work, maybe ego defenses come back. It's not a pretty feature. How often do you see that in the trials that you do? What percentage of the out of people coming through, do you think end up with worse than they were before the trial? It's very rare in the trials that we've done. But you see defenses come back. So you do see people relapse. If you're pushing out to three months plus in something like treatment resistant depression, that's more the rule than the exception.

2:08:52Sadly, people relapse. If their histories are histories of chronic depression, then while you might give them a window of wellness, sadly, it doesn't last. It's not to say that it doesn't ever last. It does. We have people who are in our first treatment resistant depression trial who are well to my knowledge today, back at work doing fantastically well. But sadly, the majority of relapse to my knowledge and need to do more psychedelic journeys. Well, they can't because it's illegal. That's been the really difficult situation that we've been up against is that we do a trial where all of a sudden this schedule one drug becomes a medicine in the trial, or at least an experimental medicine.

2:09:36We give the treatment. It works fantastically well. It gives people a remission that they've never really had for however long. And then the trial ends and they're denied that treatment and were still, if they were to have that treatment, they would be committing a crime. It's sort of a sick joke in a way, but that's that's the situation that we've been in. And that's a perfect segue for what I want to talk about now, which is what is the current state of legality in terms of or the progression towards legality? I'd also like to touch on the role of, let's just say incoming big pharma. There are a lot of startup companies now trying to capitalize on these discoveries that you and others have made.

2:10:22The landscape out there is very unclear to me. Maybe I'll just call out some silos as I see them. And maybe we can draw some bridges between them if they exist at the ground level, not the grassroots, but at the ground level, I look to laboratories like yours, Matthew Johnson's, Roland Griffiths, some laboratories at Stanford, Nolan Williams. Lavaatories studying the effects of psychedelics in human beings, so not animal models in terms of their clinical application for the treatment of depression, anorexia, I don't know, fibromyalgia, trauma. Let's lump MDMA in there as well, assuming that it all works in an equivalent way at the level of kind of where the legislatures taking things.

2:11:12Okay, so labs using government money, philanthropy, etc. Then there are the the sort of the therapists out there that are accessing what we believe are clean sources of MDMA, psilocybin, LSD to do this. They are doing it illegally. This is in the US or other western European countries because obviously it's going to differ by country who are administering these things. Sort of on the basis of what they're reading in these studies that you all are publishing, but also expanding on and experimenting. Hippie flips and combination drugs and ketamine, etc. But let's leave ketamine out right now because it's legal.

2:11:54But there's that. Then there's the, I don't want to say it's sort of recreational slash open market, black market. And here I want to raise a flag to the fact that Dr. Peter Tia did a terrific podcast on this recently in his own podcast, The Drive, the fact that fentanyl, lacing with fentanyl is now showing up in MDMA and psychedelics that are purchased on the streets of serious caution to those getting it from uncertain sources. And then you've got pharma. And then as an umbrella for all of this, you've got the FDA and law enforcement agencies which currently say this stuff is illegal unless it's being used in a can get you charged with a crime ranging from I don't want to say because I don't know but I'm up to felonies, right?

2:12:46Years in prison. Okay. So can't take it through airports, can't don't get caught with it, don't buy it, don't sell it kind of thing. So where are we going from that picture of these silos? I know things are in clinical trials now. Most people including myself are not familiar with how the different phases relate to the proximity to legality. Could you just kind of give us the landscape and touch on how long you think it will be before the people that come through your trials could then go get a prescription for psilocybin or potentially buy it without the risk from a reliable source one would hope but without the risk of getting thrown in jail.

2:13:28I used to live in Oakland, California. My understanding and please correct me if I'm wrong folks, don't trust this information and get in trouble. My understanding is that psilocybin is decriminalized in Oakland but that's not the same as being legal. So what is going on out there? Well, it was so much. Yeah, I just asked 55 questions but feel free to answer just a sub -side of them if you like. Well, Oakland's a funny one. I live close to Oakland. There are head shops in Oakland. There might be selling cannabis and cannabis related paraphernalia that are selling mushrooms as well psilocybin mushrooms.

2:14:12That's a fact. Opened it. Yeah. That's a fact. I can verify. I haven't purchased them but I've gone in and kind of checked it out like what's going on here. Yeah. Yeah. So the police aren't going to prioritize that activity, the purchasing of those mushrooms as a crime now in Oakland because of the decriminalization. So those head shops shouldn't strictly be selling. Well, they shouldn't be selling. They won't have a license to be selling. Licenses don't exist yet for that here. But let's see whether they get shut down. They probably will. I don't know. But there's a church in Oakland that say that they're selling and it's part of religious rights that they're using that church model as a loophole.

2:15:11The way that Native Americans can use peote and they have a more genuine case, I think, because there is a history there that they're trying to kind of piggyback on that. Anyway, that's sort of close to where we are right now. But federally, which is really the major inflection point is the FDA and the licensing of psychedelics as medicines to be legally prescribed across the country, across the US and beyond. That is close because the key phase, there are different phases of clinical trials and the key one to know about is phase three. Phase three trials are licensing trials. If they're successful and typically you have to do at least two successful ones, show the results to the regulators who are the FDA, the medicine regulators and say, is this good enough now for you to give me a license so that I can sell and provide this medicine that we've demonstrated as a medicine.

2:16:18So that work has been done with MDMA therapy for post -traumatic stress disorder maps have led that work and done two phase three trials. I think they've already publicly announced that the second trial had results consistent with the first. We know the results of the first because they're published and they were remarkably good, something like 67 % remission rates. And long term, I understand me as some of those remission rates for trauma or years, which is different than what you're describing for psilocybin, where people might need ongoing dosing. That's true. Yeah. Yeah. But of course, just for trauma in those trials.

2:16:56My understanding is those MDMA trials were not focused on depression. Yes, yes, focused on the trauma. So that's something because that data is being filed now to my knowledge, like as we speak, and they're anticipating a decision maybe this year with rollout happening as early as next year. I mean, that's sort of best case, I think. Could I ask you when you say rollout, who's, and it's the appropriate term for MDMA, so -called rolling, about 20 % of my audience. Maybe 50 will understand that not funny joke that I made. Who's going to roll it out? Where would one get the MD, the clean source of MDMA, meaning not laced with fentanyl, not laced with methamphetamine, not undergone any chemical conversion to some other drug, which can happen with extended shelf life, etc.

2:17:54Are people going to go to their psychiatrist to get MDMA? And who's going to be providing it? Is it going to be some big major pharma? This seems like a serious set of issues. It is, and I don't have all the answers. I do know that maps would be providing because they've done the work and they have set themselves up in a sense to potentially become the provider, whether as a pharma company, which is the big question they're wrestling with at the moment. It's very expensive to become a pharma company. And yeah, they probably deserve to make the choice because they put in so many years of hard work when all of this stuff was considered like rava, culture, party, drug.

2:18:43They were the ones that spotted the therapeutic potential. I mean, we knew there was therapeutic potential based on work going back many decades, but points to them. And I think that in my opinion, they should have the agency to make those decisions. Yeah, it's a remarkable thing that's been achieved. And I think they've done it all on philanthropic donations. I think so. Yeah, so there is this big question mark in the FDA are also asking questions about to your question, you know, who can provide this because in the phase three work and up until this point, there's been a maps training, a maps therapist training.

2:19:28And you have to do this formal training in order to be a practitioner within the trials. But now there's a question from the FDA whether that maps training can be the training that a clinician has to have to now be a provider. And when I say rollout, it's like offering this as a service essentially. And so where would the referral come from? That's a good question that I'm not 100 % on the answer, whether it have to come from a psychiatrist or whether someone's sort of general physician could do that referral. But they will be going to a provider who is licensed and certified and will have done some training.

2:20:17And there will be a consensus on, you know, what constitutes good enough training to provide. There will also be some stipulations on the basic underlying professionalism of the clinician who provides. So I imagine there'll have to be a mental health professional. I don't think they would have to necessarily be a psychiatrist. They could be a clinical psychologist. For all the dosings, I think without question, there would have to be a physician present or at least within ready access in case of an emergency. Yes, especially with MDMA because of the propensity for cardiac issues. Because of the emphetamine properties.

2:20:58And where is psilocybin in terms of the phase trials? Is it in phase two, phase three? It's in phase three. There's psilocybin therapy work being done for treatment resistant depression by a company called Compass, those trials, which are always multi -site. So there's always a bunch of teams or labs in a sense geographically spread out that are each contributing to data that then gets massed together and is then submitted as part of the phase three trial results. So that's happening with Compass right now. It's psilocybin therapy for treatment resistant depression. Those trials have just started.

2:21:40And I think the earliest estimate that I heard in a journalistic article was because I don't think Compass would say, or they wouldn't say publicly, something like 2026. 26. Wow. So MDMA is a head of psilocybin. Oh yeah, quite a few years ahead. And it's more of a not a certainty, but it's very, very strong position with MDMA, whereas the work's only just begun with psilocybin in terms of the phase three trials. But then you have this other situation of like, however many psychedelic research centers there are now, across the globe. It was nice to, you know, we had the first one in London in 2019.

2:22:26First one in 2019 is 2023 now. And I don't know how many there are, but so much has happened in such a small space of time. Yes, but you know, all these different indications I've been able to tell you about anorexia and fibromyalgia syndrome, trying to do a trial with a colleague of mine at UCSF in methamphetamine use disorder. He's got a trial going on in Parkinson's disease and chronic lower back pain and bipolar disorder. I mean, there's so much going on, OCD, almost the full gamut of psychiatric disorders, not schizophrenia to my knowledge, are being looked at. So there's so much ground, ground, you know, ground swell of activity.

2:23:16And I think these small investigator -led studies, typically they're small because trials are expensive, are going to be reporting positive results. I know what we're seeing and it will be, you know, four, let's see now, at least four trials, all with really positive results in very difficult to treat disorders. And that's just asked. And I know there's so much elsewhere, addiction disorders as well, you know, in my Johnson's work, obviously, Michael Bogey and shoots. So all this compelling ground swell, it's really something. And yet, you know, the system to really make a big breakthrough in terms of licensing is, of course, slow.

2:23:58And it's so that can frustrate people, but it has to, it has to be done properly. Else we revert back to what happened in the 70s, where there was a lot of interest in psychedelics. It's kind of interesting to me. There was a close juxtaposition of meditation. And kind of behavioral approaches to self -directed state change, encyclodelics. And meditation kind of made it through the hatch. I mean, there were some years where it was considered kind of counter -culture, who magic carpet, weirdo stuff by Western science. But now, I mean, there are tens of thousands, is not an overstatement of quality studies exploring how meditation can provide advantages for the mind and even for mental health.

2:24:49And psychedelics are now catching up, but they used to be close cousins in the cultural framework. But the problem was, I think, psychedelics were viewed as making people crazy. And university professors lost their jobs for having discussions like the one that you and I are having right now. And some people went to jail. But mostly people either left academic institutions or lost their jobs, whereas now these are some of the studies of the sort that you are doing and that are taking place at Stanford and Hopkins and elsewhere are some of the greatest magnetic pull for philanthropy for universities.

2:25:30Donors are very interested in supporting these sorts of studies because they and their family members and people they know suffer from psychiatric illness for which the current big pharma approaches simply have not worked. So it's sort of interesting to me that what once was seen as kind of poison is now being viewed as a potential therapeutic. It's not just interesting. I think it's hopefully it speaks to the evolution of the human species. People seem to be coming more open -minded about becoming more open -minded. That's a good one. Yeah. And yet, yeah, there's so much that's happening so fast.

2:26:22And there are elements of, it's complexifying the space. There is critique. There's been some bad practice in psychedelic therapy boundary crossing issues that have caused some scandals. That's too bad, isn't it? Yeah. Well, I think to the gene therapy, right? It just takes one bad incident. You know, gene therapy was on a fast track three decades ago and then what sadly child died in a gene therapy trial. And it's like shut down gene therapy practically for half a decade and then it slowly started ratcheting up again. Gene therapy broadly defining now we're in the age of, you know, potential directed gene therapy using CRISPR and things that sort which makes people, some people cringe and other people very excited.

2:27:07You know, if you have Huntington's in your family, CRISPR is like the most exciting technology ever because you could potentially eliminate it from your family line going forward, of course. So I just really hope that we can be balanced. Does this all plays out because it could go similar way given the stigma, given the history that people be very twitchy with, with some isolated incidents. And over generalised them perhaps. In a sense, it's shining a light on them, I think, is important that that has happened recently as important because it really drills home how important it is that this work could be done right and what the necessary safeguards and standards should be.

2:28:00Yeah, it won't be an easy road forward. But let's hope, you know, we've got to hope that it succeeds because current treatments, you know, people talk about the mental health crisis and to your point earlier about anorexia rates. It's not always actually the case when you look at the epidemiology, when you look at the data that you see a big inflection in, you know, diagnoses or cases of psychiatric illness, I would say it's more that the treatments haven't moved. They haven't really progressed. They haven't got any better since the 1950s or less. And new drugs have been more of the same. So there haven't been any paradigm shifts.

2:28:47And that's why I get a little impassioned when I talk about psychedelic therapy and that point that this is something different. It's not, you know, a drug every day. That system is not cutting it, you know, do we really want to keep on with that system? Sure, you know, not everyone will want to trip and that will terrify some people so much that they'll just want to be on their lexapro or a non -psychedelic psychedelic or whatever. And of course, you should be allowed to have those options, of course. And the more options are better. But I think there is a great value in really understanding what psychedelic therapy is.

2:29:31And and I think when you do, you realize that it is a major paradigm challenge on many levels. And the fact that it's different might be its greatest appeal at the moment, I think. Well, I am certainly grateful for your passion for the potential for psychedelics to be added to the array of potential treatments. And I really also appreciate how much you put it in there alongside the other treatments. Maybe even combination with other treatments as opposed to saying this is the thing that's going to cure everything. And yet, the passion that you have for this potential paradigm shift, the one that really appears to be happening at the level of clinical data now is so important.

2:30:18So I want to extend a voice of gratitude for that. And for the work that you're doing, I mean, I've been outside of this field, but as an neuroscientist, I've been paying careful attention to it. Really for the last five, seven years or so. And it's abundantly clear that it is a small group of individuals who are really thinking in terms of how the system works now and what needs to be done in order to change the system for the better, like yourself, that are really the driving force behind this new movement or paradigm shift that without question is going to lead to improvements in mental health and physical health outcomes.

2:31:00So I just want to say thank you for that. Also, thank you so much for joining us today to share this immense knowledge set about the history of psychedelics, what they are, what they aren't. Their clinical applications as seen in your laboratory and other laboratories. I'm sure people already noticed this, but you're incredibly generous in terms of attribution and also in your caution about explaining how some of the results, in particular on anorexia fibromyalgia, are perhaps preliminary, but very exciting. They're not published yet anyway. We wouldn't call them preliminary. And also for touching on mechanism that is not just about people feel better, but point it to some potential underlying mechanisms in terms of connectivity changes and on and on.

2:31:47So thank you so much for your time today. Thank you for the work that you're doing. And thank you for the work that is sure to continue. We will provide links to studies in your laboratory, links to your laboratory, so people can learn more and support in the ways that they deem appropriate for them. But just thank you, thank you. Thank you. Such important work you're doing, Robin. Thank you, Angie. It's been a pleasure. Thank you for joining me today for my discussion with Dr. Robin, Carhartt Harris. I hope you found it to be as informative about the science and clinical uses of psychedelics as I did.

2:32:20If you'd like to learn more about Dr. Carhartt Harris' research or support that research or inquire into being a research subject in one of his laboratory studies, please see the links in the show note captions. In addition, please see the links to his Twitter account and other social media accounts also in the show note captions. Also in the show note captions, you'll find a link to Dr. Carhartt Harris' Twitter account where he regularly posts about new advances in the field of psychedelic science. If you're learning from Endor and join this podcast, please subscribe to our YouTube channel. That's a terrific zero -cost way to support us.

2:32:52In addition, please subscribe to the podcast on both Spotify and Apple. And on both Spotify and Apple. You can also leave us up to a five -star review. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or suggestions about guests you'd like me to include on the Hebrewman Lab podcast, please put those in the comment section on YouTube. I do read all the comments. Not so much on today's episode, but on many previous episodes of the Hebrewman Lab podcast, we discuss supplements.

2:33:22While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like improving sleep, hormone support, as well as focus. The Hebrewman Lab podcast is proud to have partnered with Momentus Supplements. If you'd like to see the supplements discussed on the Hebrewman Lab podcast, you can go to livemomentus spelled O -U -S, so it's livemomentus .com slash If you're not already following me on social media, I am the Hebrewman Lab on all platforms. So that's Facebook, LinkedIn, Twitter, and Instagram. And on all those platforms, I post about science and science -related tools, some of which overlaps with the content of the Hebrewman Lab podcast, but much of which is distinct from the content on the Hebrewman Lab podcast.

2:33:59So again, it's Hebrewman Lab on all social media platforms. If you haven't already subscribed to our neural network newsletter, the neural network newsletter is a monthly newsletter in which we distill down at the essential points of particular podcasts and we list out toolkits, such as toolkits for sleep, toolkits for neuroplasticity, toolkits for optimizing dopamine and on and on. All of which is available at zero cost. You simply go to HebrewmanLab .com, go to the menu, scroll down a newsletter, and supply your email, and we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr.

2:34:30Robin Carthart Harris, and last but certainly not least, thank you for your interest in science.