Dr. Robin Carhart-Harris: The Science of Psychedelics for Mental Health
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Welcome to the huberman lab podcast, where we discuss science and science space tools for everyday life. I'm Andrew huberman and am a professor of newbie logy and alphabet gy at stanford school of medicine today. My guest is doctor Robin kar heart Harris.

Doctor car heart Harris is a distinguish professor of neurology and psychiatry at the university of california. Sentences go, he is one of the leading researchers in the field of psychoanalysis and how they change neural circuitry in the brain. His laboratory is responsible for understanding, for instance, how slice ban, also sometimes referred to as magic mushrooms, change neural circuitry in the brain, such that new ideas and new forms of learning occur.

His laboratories is also responsible for Carrying out various clinical trials, some of which have demonstrated that appropriate dosages of slice ivan can alleviate major depression in more than sixty seven percent of people that take the drug. Now this is not to say that everybody should take Sullivan in today's discussion describes both the clinical trials and why treatments with psychiatrically in some cases work and in some cases do not work in order to treat major depression, as well as discussions around soli, ban lyor, gic acid, diethers ID, sometimes also referred to as d as well as d mt. And how these change the brain, and how those brain changes can relate to changes in mental health as IT relates to depression and other psychic atrac chAllenges, as well as how psychedelics are being applied in order to general circuitry for sake of expanding different aspects of the human mind, including creativity, intelligence and much more.

During today's discussion, doctor car heart Harris teaches us about the history of the study of psychiatrically, as well as how the legislature, that is, the laws surrounding psychiatrically, are evolving in the united states and elsewhere for the use of psychiatrically to treat psychiatric chAllenges. By the end of today's discussion, you'll have a third understanding of how psychotic lcs work, both in the short term during the actual journey or trip. In fact, much of my discussion today with doctor car heart herr's talks about the different aspects of the psychedelic journey and how those relate to therapeutic c outcomes.

And of course, by the end of today's discussion, you will also understand the long term effects of psychology. S, that is how they can actually required the brain. Before we begin, i'd like emphasized that this podcast is separate from my teaching and researchers at stanford.

IT is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, i'd like to thank the sponsors of today's podcast. Our first sponsor is element.

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Doctor car heart Harris, welcome. Been wanting to talk you for a long time. I certainly known who you are for quite a while because I place you in this very small, but very special and important category of researchers who has been pioneering the use of psychedelics for the treatment of specific clinical conditions and really Carrying the torch for essentially the entire field.

So I want to start with the a voice of gratitude and say, thank you for doing this incredibly important work. Could you tell us a little bit about what psychic licks are? In fact, i'm curious to how the name psychiatric ever came to be and what you think they potentially revealed about the workings of the brain. And then .

we'll talk about the clinical applications. Well, even that is a kind of hot one because the opinions differ on how to define psychiatric.

But perhaps a good starting place is to start with the etymology, whether the word come from and IT was a bit H X communicated a living in in canada, humper, who was due to present of a paper at a national academy of sciences meeting on psychosomatic tics, drugs that mimic aspects of psychosis in their action. And certain drugs like my clin see one hundred and fifty six and L D. Were on on the bill.

And he felt dissatisfied with them being under this category of psychosomatic tics and felt that the signature psychological effects of these compounds went beyond just miss king psychotic symptoms. And so he wanted to find a more act term to speak to in a sense of principal component of their action. And he jumped IT down a few different h possibilities, about a dozen or so, I think.

And one of them was psychedelic, actually had started as an, ended up being psychodeviant. And he had a correspondence going on with another brit also living in the U. S.

Or just hug a, where they were playing with. Some are terms to refer to these compounds and and in the end, osmond, one with psychedelic. Can he had this little duty of to fathom hell or saw Angela? Just take a pinch of psychiatric that's we've put the disco.

And so what does that mean? It's to ancient greek ard psyche means the human mind or if we're being uh, as he true to the ancient greek IT means soul. And then the other component means to make clear what to make visible or to make manifest or to reveal to all of those work.

And it's it's a neology m it's a made up word. But IT does have that agent greek origin and is speaking to this principle that these compounds reveal aspects of the psyche of the human mind, the soul that are ordinary, not entirely visible. And so that's yet to ology and it's wonderfully poetic, but I happen to think it's also very accurate.

It's a useful term because it's sort of you might say violence nonspecific IT doesn't say you going to have a great time or that you're gna go mad uh it's more that IT revealed a psyche and IT could be halliss but IT could be heavenly and uh so that's the etiology and also a bit of the psychology um and so as you know, pointing to the phenomenology the subjective experience. But there's also a farmer ology here and quite recently there was put out a consensus statement about psychedelic that's really referring to what we call the classic psychiatric, to say that these are all compounds that work on a particular receptor in the brain, the serotonin two, a recept. And that's another way that we could define these compounds. I said this ones a little hot because I move the view that while the pharos gy is really useful, how the drugs were chemically, you can't avoid the phenomenology. And if we're true, the etiology where the term came from, then we must recognize them and we cannot neglect the subject of experience.

Thank you for that beautiful description of what brought us to today in terms of using the word psychodeviant xs. And now it's throw around all the time. Yeah yeah too much and and i'm guessing uh not guessing.

I'm certain that it's uh also used to describe many compounds that don't touch the five h two five H T two a the service one and two a receptor. So there is a broader categorization by most people and um and we interesting to see where all the nomenclature and naming goes for the time being. I'd love for you to tell us a bit more about this idea that psychiatric um however one defines them, can reveal something about the mind that can't be revealed otherwise.

Are you talking about the subconscious? I mean, you know psychologists and most famously frayed but also Young and also neuroscientist I think um think about subconscious processing. I think perhaps the most silent example for me that's outside the realm of of anything psychedelic would be blind sight.

This fomenting that you take people that are blind but still have some connectivity in their brain, and you present them aboard with a computer screen with different number of dots on each side. You say, how many dots are on each side of the screen, and they say, what do you mean? I can see the screen and blind, he said they would just guess.

And their guest rate is accurate far more than chance would would predict. So they have so called blind side and people of said, well, this is the subconscious revealing itself um there's no seacole drug involved, but what you're describing is a pharma logic indo state that reveal something that Normally. Should we assume is masked or that we are a oblivious to, uh, even though it's expressing itself, what does that mean for these drugs to be revealing something about the workings of the mind that would not be obvious to us otherwise?

Yeah so so the example of blind side is interesting, but it's different. Blind side would be a referring to non conscious processing, maybe implicit processing. So stuff going on in the mind, in perception in a sense that is below the threshold ld of consciousness warehouse, but yet is influencing you.

So it's sort of it's kind of related, but it's different. So in in depth psychology, psychoanalysis, psychodeviant psychology, you know, sign friend caryn g and so on. We talk about the Young conscious, and there is more about the kind of blood and guts of the human county and the human nature. Both the personal unconscious say things that you might not want to necessarily be consciously because it's painful, so that that's the repression. Ask back, pushing IT out of conscious awareness.

repressed memories .

in particular. Yeah, like traumatic memories, difficult relationships who could be complex raumer. Not necessarily just a specific you know index trauma but a series of trauma um and then you have the collective unconscious, which was really called you contribution to say that um you know there's a trans personal quality to the unconscious these aspects about humans, not just this individual human as aspects to our my our minds are psyches that are not fully available to conscious awareness but come up in certain states you know psychoanalysis when crazy for dreaming is is their royal road to a knowledge of the unconscious that was royd um but we now know what psychiatric and this was what dream the area was discovering literature that was speaking to this particular action, the psychedelic action and was saying that when these drugs like hell sy salicylic found magic machines um when they used in in psychotherapy um material comes up that maybe may have been repressed the the um is of you know therapy tic value an awareness and insight of this material seems to catalyze the therapy process with and strong emotional release these catheter experiences and and insights you know whether the inside the personnel um or whether the transparent no um but for me this is really where the me of IT is with psychiatrically and classic psychiatrically in particular likes of compounds like l and and solar.

Ivan, I would say that if IT wasn't for this action by classic psychiatrically, we wouldn't be so interested in psychiatry ics. I I think we only had compounds like catamenial cannabis that could be said, broadly speaking, to be psychiatric like I don't think you necessarily would have captured the world's attention in this psychodeviant are right now actually take a major gap to fill is this principal action of the classic psychiatric what does what does this mean that i'm referring to psych revealing, what is that? And suppose where i'm going with this is what is that in terms of the biology as well? What's going on in the brain and the body when people become aware of things that previously they weren't fully aware of?

I'd like to talk about some of the clinical trials that you've been involved with, in particular looking at slynn, as you mentioned, the principle holus psychiatric agent in magic mushrooms. I'd like to start with a kind of nutty n bolts question just so that everyone's on the same page. I've read the papers that you've published and that others are published in this area.

And typically on the dosages used in these trials are twenty five milligrams of Sullivan. And we talk about one recent trial in particularly that compared red twenty five to ten milligrams to more frequent use of very small amounts, one milligram over three weeks. For instance.

However, when people talk about magic mushrooms, they often talk about gram doses of the mushroom because i'm assuming that they contain milligram dosages of slynn. Here, we're not encouraging use of any kind. These are clinical trials.

But for clarity of understanding what is the conversion, typically like one gram of magic mushrooms will contain how many milligrams of silicon on on average because what what i'm trying to do here is, is calibrate people to this idea of microdot versus microdot, and that's fairly straight forward to do with respect to the clinical trials. But then in the a lot of the lay discussion around this, you hear about heroic doses versus microdot. And so I think there's a lot of confusion. So if you would um educate us on this idea of what's a micro dos and perhaps also how many milligrams of Sullivan contained in a gram of coding, quote, magic mushrooms.

So well a micro dice is is uh neither of this so that simple but the fun it's a fun chAllenge microdot. One definition is that it's a dose of typically a classic psychiatric like a or solar yb um that is that has sub acceptable psychiatric effects like IT doesn't put you into a noticeable alter state of consciousness that feels like your tripping and if that was elastic IT looks as though the fresh holders around about, let's see, ten, eleven, twelve microgram. great.

yes. So ten micrograms of L D are you saying will not induce visual hlubi ation in most people?

So it's it's that's thresh hold level that's about the level that that some people who are a sensitive could feel IT. But if you were to talk to the um microdissection rules, they might say that that's kind of the ballpark for N L D dose that you would consider a microdot and then you would take sort of semi regularly. It's typically something like one day on one day you are for one day on two days of this kinds thing.

There's different protocols and yeah so you need some like jim faden um uh one of the popular ries of microdot. I think we'd say that a true microbes should be so perceptable you shouldn't feel that yet. The assumption is it's gonna change you in some way on a kind of trade level more than a state level um maybe behaviorally um and the typical story goes that will improve well being and maybe maybe I could improve certain aspects of cognition, say, related to creative thinking.

Um I emphasized that maybe there because that's another angle with microdot. We're kind of waiting for some compelling evidence as things stand right now, i'd say we lack that compelling evidence is some suggestive stuff. But often the study designs on as strong. It's really hard to do a study with microphone because you need to have permission to give people a microdot that in a for practical reasons they would go home with.

And um otherwise you you're requiring them to be in the labs say three times a week for x number of weeks to meet the criteria of a course of microbes, which might be you know two or three times a week to say a month. And that's hard thing to do in a lab study. It's expensive.

You'd need to do that against a suitable control. So a proceed control and there is a study that being done in new zealand um that has some interesting preliminary ary data that did I think kind of did the design right um but hasn't been published. Yeah, i've seen some positive findings presented around improvements in in mood, but it's a bit early.

Get too excited about that. Need to guys repair of you and all that but asking stand you know the evidence is pretty thin and and and we have to be honest about that. We did quite a creative study uh with my colleagues at imperial, the guy leading that ballah h shaea ti ongry an chat, did a really creative design, very much as brain child instructed people to do their own blinding, their own, plus IO controlled blinding of their own microdissection.

So this was a classic citizen science study, like do IT yourself science, where they would get their allies tags and shot them up, put them into jail, captures, so pick and have other captures that the police boys, that they just close empta captures and then knows a whole barcode scan technique so that you you kind of shut them up, you know. But they've got the bar code in the Q R code, so you can bring the code later run. But once you've shuffle the mark you know longer, know which ones have have the the microbes in in which runs are empty.

Was this L, D.

This was L D. Also tried IT with mushrooms, but the issues with the mushrooms was people with birth sometimes IT belt and and then they have this mushroom taste so that any instructive people to get some like non psychoactive mushroom material to put in size.

really an easy study.

an ezy study. And, uh, IT was, I love that kind of science in a real creative first move, a kind of science and the result of fascinating because the short story is the micro saying didn't um compelling ly beat the policy but he didn't and he controlled because he asked, uh, he controlled for expectancy. So people is positive expectancy, which is in a sense of vehicle that Carries the process by response.

Why you ever play boy is the positive expectancy can drive a therapeutic fect to, you know, a large extent. So he measured that prey trial and then used IT to kind of correct for the response. How did IT work? Those who got a plus boo, but thought they got a microdot did, as well as those who thought they ve got a micro dice and dict a micro dice.

So IT was the bigger effect, that the majority of the effect was in thinking that you got a microcode. So in a sense, IT was a Victory for the power of the proceed by response. And IT created all sorts of controversy. People don't want to believe that, you know that kind of thing, but that's the beauty of science isn't IT that science is not about what you want to believe that right? There is the beauty of science really.

I love that experiment of kudos to them. I'm not going to attempt to say his last name try.

yeah. No, no.

Thank you. You got IT. You were involved in a clinical trial that was published last year comparing twenty five milligrams of silicic bon to ten milligrams of silica bon is a very to A A drug called s yeah and this one milgram over three week dosage wanted to discuss the results of that study a bit um and some of the other trials that you've done involving suicide de and for depression, the treatment of depression, could we calibrate ourselves twenty five milligrams of Sullivan is is that what what it's can be a perceptable dose presuming hu cino and all that and is that a what one would find in um i'm guessing here if I accurate this doesn't not mean that um I have experience .

here but two two grams of we think yeah sorry I miss that s one the time but yeah twenty five milligrams of solar ivan would be we don't know and and it's important that I say that because I wouldn't want people to hear my answer here. And then use IT to calibrate their own dosing and mushrooms and get IT way off so it's guess work.

And I would love to see someone to proper study on IT and you know, look at the solicited content in a given massive philosopher mushrooms, magic mushrooms. But to my knowledge, that hasn't really been done. Someone like post stand has would give a Better answer at here.

But I think the percentage within the mushroom mass is some of soybean in the mushroom mass and styles in which is a metabolite. Solar, yvan, is something in in one percent, a little bit. Ha, maybe range.

okay. So one one gram, one thousand milligrams of magic mushroom would contain about ten milligrams of Sullivan.

broadly speaking.

Yeah great. That helps calibrate um and I think again, just allows the lay person to understand a bit more where we're headed with these suicide and trials and and the results. So we don't have to restrict our discussion to just that one clinical trial.

But if we include that one and compared to some of the other trials that you've done, I mean, your laboratories is seeing phenomenal, in my opinion, phenomenal results in the treatment of otherwise intractable depression, major depression with so many people suffer from from two um I suppose there are two sessions of using, solicited and in these ranges of ten to twenty five milligrams. Do I have that create? okay.

Could we talk a little bit about what people typically experience during those sessions that allows this phenomenal transformation of mood and state and trait um as well? And i'm especially interested in whether not IT is the experience during those sessions that is the trigger that's necessary for the the transformation from a depressed to a non depressed state because the the impulses to think IT is that what one thinks and seas and hallucinates is and here is so vital. But of course, these drugs can create neural plasticity changes in our neural wiring, presumed ly for long periods of time. So what are your thoughts on the the experience itself? And maybe for those who have not done these compounds before, you can explain a little bit about what's typical for people and what you think is leading to that incredible, positive and pervasive change in mood, state and trade.

I would I would say that is more than impulse. That is a leading us to think that the experience is important is really data and and converging evidence now. So independent teams, independent studies are converging on the magnitude de of certain kinds of experience. Rated yes with subjective rating scales is predicting therapy to outcomes pretty, pretty strongly and very reliably.

Um and so that's guiding us now could you say, well, maybe those experiences are some kind of eppy phenomenon of say, a central brain action will absolutely but then all experiences an epi phenomenon by the principle and yet we care about IT you know and IT matters uh to us and in our human relations with each other so I think IT doesn't matter to A A human being when there in a say, a solide de therapy session. And as the drug effects begin to come on and the body starts to feel a little strange and tingly and the there's some initial anxiety, and then in their minds eye, they start to notice patterns and maybe colors. And then maybe those patterns deeper and their dynamic, they have this fascinating organic quality.

Are the patients in your studies typically using a an I mask or so they're in the im as so eyes close, that's why you said minds eyes as opposed to looking out into yes.

And one of the major differences to psychiatric therapy versus taking a psychedelic is you shut your eyes and it's it's a world away from taking a psychiatric yeah arrive or something you know in a sense good luck with that um but in psychiatric therapy yeah it's it's you know settled conditions. There's music playing. And what i'm describing here is very much the default actually you know very little variability between the different sites that have done this work on these conditions. And typically it's two people ideally mental health professional was that at least one whose the psychiatrist that are clinical psychologist to some other kind of psychiatrists or psychiatric um but ideally two who meet those quiet area with a individual whose injured ted the drug a music playing throughout kind of runway into taking the drag. And then throughout that this continue.

We are music with lyrics or .

or without lyrics to begin with. And the music typically is spaces to begin with and then builds and becomes atmospheric. Ah there might be, I don't know, some tribal drugs in the distance or or something as as IT developed or like the sound of a bird in the distance you and I A birds call and then as he gets into more stronger drug effects, the music um starts to cox a emotion and very intentionally in strings, for example, would come in and it's IT would be an interesting experiment and one that we d love to do actually to see whether if you were to pull that out, whether the the psychology experience would be as emotionally intense as as IT is in psychiatric therapy. When you have music, there is a default.

And across the board, people should find this remarkable because this kind of is all of the publish studies that are now, you know, having such an impacts on psychiatry and beyond. Have music, there is a staple of component. And we just take IT as assumption that, that needs to be I tend to share that assumption, but is remarkable that IT hasn't been tested properly.

But is that and you know, if you were to run with that and and if you were and I had a kind of critical agenda, you would say, well, this is music therapy, you know, uh, why making all this first of our psychiatric, it's music that's there in all of these trials is all these fantastic findings. So there is something to that, you know. And this will take me up probably to talk about psychiatric therapy being a combination treatment. We have a hyphen between the two because I share the hypotheses ah 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 psychiatric therapy, the hyphen just like cart heart hair. I'd like to take a quick break and acknowledge one of our sponsors, athletic Greens. Athletic Greens, now called ag one, is a vitamin mineral probiotic c drink that covers all of your foundational nutritional needs.

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This is extremely useful to hear because I think most people think, okay, psychedelic, whether they have experience with syc dogs or not, get to visual halcon ation, some auditory hallucination, some synthesia, some visual auditory blending, some medication ation. You know, rubbing a surface and and being able to illicit the sounds in one's mind um of course IT sara. But so seldom do we actually hear about the the specifics of these clinical trials in a way that, for instance, points to music as one of the perhaps key variables.

Now you mentioned that as people enter these psychology says that there's a little bit of initial anxiety. About a year and a half ago, I had a discussion with doctor Matthew Johnson, who's running some suicide van trials. John kin is know, and he mention the critical importance, at least in his mind, to this idea of the patient court and court letting go or allowing the experience to take them some place mentally as opposed to trying to constrain their sensory and cognitive experience.

Um I course what your reflections are on that on that idea and why IT might be so valuable clinically um and this is back to this earlier discussion we were having about the unconscious or about psychological revealing something that there all the time but that we don't have access to um you know and again, i'm struggling to find the right language for this because we don't really have a neural mechanism like top down in addition or something like that to explain how this you know unconscious might be uncorked in the psychedelic experience but to make IT quite simple direct. How important do you think IT really is for the patient to feel like they are calling letting go? And what in the world is letting go in biological terms? Ah 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 the unconscious into consciousness or unconscious ous material into conscious awareness. It's a it's a wonderful chAllenge, is a huge chAllenge, but it's a chAllenge to embrace and letting go very much is again a staple component to have 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 trial, the first trial of of a psychiatric in uh formally diagnosed depression, you know where that was the target population and depressed population is the first modern study to do that and um we visited hopkins friends iron and were mentored on how to do the guiding bill Richard merry cosme they were just so um brilliant and and in a wise in in the um in the guidance to us as to how to do the guiding in our trial and so this phrase a trust let go be open you will hear a lot I don't know who fail IT should be attributed to but I would attributed to build uh bill Richard yeah everything's borrow do you probably got IT from someone one else but is such a key principle and it's almost like a mantra that you're trying to instill in people trust, let go, be open. And those different components where the trust is about therapeutic report that again, and this goes beyond just intuition. Now we formally mentioned thread at report.

We do IT even. We're just a single item, a visual analogue scale item, the subjective rating scale item on the morning of dosing. And we find that it's a it's a significant predictor of the quality of the experience that you have under the drug in in the psychedelic therapy and then the therapy to outcomes x weeks or months later.

Um a very powerful kind of chain of a sort of predictive components, the trust essentially important. And again, not just the intuition, but the data pointing to that let go. There's a really 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 um a willingness to go there to confront, to be inquisitive ah something that easier said than done can be terrifying. And I when you're dealing with a very vulnerable population, is probably more the rule than the exception that they Carrying some significant adversity, life adversity or Frank trauma that they've suffered.

And so that message of be open, be willing to confront and to go there really and I is really powerful um and that that's how IT plays out and and often the arries struggle, there's something going on that is I don't want to be feeling this make us stop that can be nigh. Marriage at times that is very, very strong. And with these big dices that we give, it's uh it's very strong and actually a student that I ve worked with um I think now doing A P H D H every brower is working on a fantastic project characterising the different phases of the psychedelic experience where the early phase is dominated by a negative emotions and and neck negative evinced feelings of anxiety and struggle. And then it's a different story in the latter half.

Could I ask about that for sure? What I think that's fascinating and important to analyze the different phases. And again, i'm delighted here because people typically hear about a psychiatric journey, but we never really hear about the the kind of steroid c components of the beginning, middle and end of that journey that there is a peak and that there's a kind of a pair shooting down and is set up. But um when you say that typically there's an anxiety, maybe some negative violence in the early stage, do you mean about the sensations people are experiencing or about some prior event that's been called to mind that they're remembering? Um likewise for the positive phase of the psychiatric uh, journey or trip are people they still call the trip yeah alright for the I will use trip for the psychology trip.

Are people feeling positive about the experience like a like there's been some sort of breakthrough or there in a commerce state? Or is IT that they intend to be focusing on prior events that were positive? So in other words, is there a threats through of some concept that comes to mind for people maybe about an earlier trauma, or maybe about a sense of self, for a sense of other forgiveness, you know, could be any these things, but what do we know about the kind of find .

our details of all that? I would say the initial um struggle is more against the general drug effects than pinning IT on on something specific. It's more that you know Normal awaken consciousness.

We have a sense, generally speaking, if we're well or well enough a sense of assurance about what's what you know is a table here and and so and and and we have that sure in this in to an extent about ourselves as well. You might be a losy, but we have IT. And what the drugs doing is, is 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 IT feels like I could be dying.

I might lose my mind. Yeah, I never .

those two are the classics is, oh, but I might, you know, I might know that I ve taken a psychiatric, and I might even know a bit about psychiatrically, but I still fear that i'm gonna go mad.

All the I know that and I generally speaking, these drugs that have I hi um you know fertility risk, I still think i'm gonna die here and it's just it's very palpable and that and that comes up so yeah that's that I mean, those of the core fears, those two and very reliably that comes up and it's really like a basic drug action. It's those dependent that is a basic drug action that is forcing something about the nature of the mind and the way it's made up that makes you feel that way. Oh, but IT feels like i'm losing my mind or IT feels like I could lose my mind that I could go insane or that maybe i'm i'm dying here and this is bad. Yeah.

you've talked many times before and i've done really wonderful work looking at the changes in communication between different brain areas, while under the while, people are under the influence of psychiatrically and I think that is stalled of those data. Correct me from wrong as that compared to the non psychiatric state that under psychiatric influences there is far more I just call interconnect vy or a communication um between a brain areas that typically aren't communicating, which probably is not surprising to people given the the subjective effects of these of these drugs. What is the evidence that after the psychedelic journey is over that some or perhaps all of that enhances 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 we've had a some recent findings in in that direction where yes, it's true. And you know the picture that says a thousand words, some people might be familiar whether these two circles um project that we did in collaboration with some researchers where ordinary the communication is going on um within systems like other regions of the visual system will be speaking mostly within the visual system will be a kind of the click inas or a modularity to the quality of the communication in the brain and then the cool finding with soybean was the first paper, is that the communication yes IT sort of transgender these modules and becomes much more into modular crossing different modalities. And that affair correlated with the magical ude, the subjective effect. And we replicated IT with elastomer sing different methods and new paper come out soon where d nt showing, uh a similar effect, a bit of a debate about what regions are most implicated. But the general effect of an increasing global functional connectivity is what we call IT or global communication in the brain.

and this is well under the influence. Putting people into a brain scanner while they are under the influence of the drug is right. That itself must be a quite an experience, given that these scanners are small tube here in a bite bar, you got a bite bar in your mouth that's IT a ite a study.

You don't always have a big bar, least the site, alex, but yeah, you gotto keep your heads to and, uh, and you have the loud, uh, M R scanning is going. But because it's regular, there are too many surprises. So it's actually surprisingly tolerable in .

a hospital settings. So you not worried about what would happen if you had .

a cardiac events. Profession was around and you know most people generally tolerate that setting quite well, surprisingly well. But yeah, we do all that and and yes, we do see that um opening up of the communication across systems in the brain and IT does speak to a kind of intuition about the subjective experience that different modalities might be blending with each other is sorry for interrupting but .

I have to ask is IT thought that the activation of the sir tone into a receptor is what's responsible for the increased communication between brain eos that under Normal circumstances would not be .

communicated? yes. So there's a few reasons why modeling work the computational modeling work, the first identifies whether two area sectors and then looks at models its basic effects on your activity um will recapitulate the the or um recreate the effect that we see actually in the data with the scanning. So doing the computational modeling you can see the same effect by knowing whether to whether the key receptors are and then making them do a certain thing that we psychiatrically.

I can imagine two possibilities, and I think its important to distinguish between these two. One possibility is that the activation of this settle into a receptor leads to increase connectivity, and thereby, auditory and visual, whose nations emerge, changed patterns of thinking emerge at sea. That 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 phone enon layer on top of some other effect of the psychiatric drugs impacting access to the to the unconscious fluctuations. In other words, is that the increased connectivity that's leading to the subjective experience? Or are those two things happening in parallel?

Will they happen in parallel and they map to each other? But the question of causes, what causes what? Uh, is the tRicky thing where I I would suggest the the the quality is circular that they influence each other and um this gets a bit philosophical but a kind of matters because otherwise you know that's a trap that is easy to fall into uh, where you're thinking that is all about the brain action causing the subject of experience and that's typically what we do in cocoa sive.

Um it'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 causes. That mind also interacts with brain and it's so hard to pick the two apart. And there is a kind of essential jewelry ism where subjective experience is the thing in 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 nowaday, there is a bit of a movement within the scientific community that study psychic alics 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 psychiatrically like sicyon in and here, or throw M D M A.

And they are, although classically not a psychiatric, it's gets lumped in, get back to that later, but that do not produce hallucinations or massive changes and subjective experience. Actually, I think this is what initially got us into conversation on twitter, as I had learned about this paper published out of a group, U C Davis, that essentially modifying psychiatric xs so that they have potential therapeutic tic application for the treatment of depression, but zero holus an gene properties. yeah.

And I thought, wow, this is going to be a very controversial thing in the world, right? Because the history of psychiatric, as you point IT out, has been one of people accessing different modes of thinking, feeling, seeing things these and letting go trust inside of a theraputics 上 ship。 And here we have um I don't want to say farmer because it's not really farma, but we have laboratories.

We are trying to tease apart the activation of receptors independent of all that subjective experience in order to essentially treat the same conditions. I love you to comment on this where you think that might be going um and you know whether or not you think that's the writer the wrong approach, if has any validity. All where IT .

is farmer is just smaller farmers sort of start up farmer bit.

okay. So the former would like to have drugs that can cure depression but don't .

make people pollution ate is that they would and patients might and the system would love IT because the system is used to IT.

It's medicine, right? And he doesn't give this this mental imagery of, uh, you know the summer of love and safran ces go or of know collide scopas right into more yeah you can imagine the more to be careful with my wording here. Those who would not be inclined toward that would might embrace a thai UTC that is strictly effective at treating depression .

with no halcyons yeah and IT doesn't look like in a an individual lying on a safe crying there out eyes out about you know the life that they've lived and that deep cathos being life transforming is very different from that model. Um i'm schedule of IT. Um my for a few reasons.

And the one is that I I can't see the logic. Um I can't see the pieces fit in a way that's compelling. And I also schedule because I think IT could easily be wishful thinking because of that point that patients would like IT and the system would like IT. And I just can't you got a bear that in mind as well. Um so wouldn't IT be convenient you know if that were true and you could get the therapy action without the psychology effects on the way that's .

a little bit of what micro dosing seems to be designed to do. Like he said, take dosages there below that that perceptual or awareness of some effect threshold over a longer period of time in an attempt to pink the circuits or twist, you know, alter the circuits, but not pollute and ate, yeah, not paris.

So if if microbic ing can do that and it's unacceptable, the micro dizon isn't psychiatric action. Because where's the psychedelic action? When psychiatric, when defined, mean psyche revealing? You're not getting that effect.

You might be getting the pharmacology. You might be getting some direct serotonin, a recept agonising so IT could be driving a therapy response. But you can get that with S, S. Arise as well.

And so my point is what what new? Okay, maybe it's a bit new. People are now developing direct to a agonists rather than in direct through a serret and release, or like this, selective serotonin uptake inhibits the assize like legs surprise.

Are there any asserts that selectively agonize, which folks, by the way, means activate in a good way? Agony sound terrible of those not form. I think that mean the disrupt, but they can activate the everyone into a receptor.

Are there any drugs that will do that that are not psychiatric? I'm not aware of any. But then again, i'm not a first .

college there any licensing used as medicines in psychic as I had this debate um recently on social media and I couldn't see uh I couldn't see a compelling example. I saw two, a agonies that we use for other things. You have a compound like lisa ride used in treating parkinsons, but actually it's .

more of a dog mine.

A is .

a selective .

serotonin to a reset stimulator, an agonist that IT isn't psychiatric. That is therapeutic, psychic. And the answer firmly is no.

I haven't seen IT yet. Will they develop one? Well, for patients sake, I hope so, because IT would be great. Let's wait and see. If they do, my doubt will be psychiatric.

And I doubt IT would have much to do with psychiatric therapy and IT would be much more like the system we used to of chronic pharmacotherapy. Take your drug every day. Let's let's hope they find IT and IT works for patients sake. But as things stand right now, i'm a little skip to call now some of the findings that are being seen that are really exciting, fantastic work being done showing things like increases in the communication components of neons dangerous growth, a spine growth, a synaptic spine .

growth yeah by the way, fox just interact for not a necessarily spine, the bone, you know, not the three row, a column, but bines are these little like little tiny twigs with bulbs on the end of of neurons that are allowed for communication points between neurons. So neo plastics is often associated with growth of dendrites and spine, and of which is Robins referred to.

That reminds me, and I just want to make sure that we closed the hatch on the early answer because I inter rupp t to you, is the increased connectivity between or communication between brain areas that 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, let's say I come in to your clinic.

I'm an subject in in your experiment. I'd take to come in in the morning. I do my psychiatry journey five, six hours later per shooting back to reality as we call IT. And then I go home. Increased connectivity last for how long? And how long are the structural brain changes occuring?

What you asking fantastic questions and and partly because we don't have the answer yet, but we do you have some we do have some data. And so we have looked at first for the in a sense of functional plasticity or what we assume IT to be or at least the functional changes, the increasing communication across systems, um that increasing global connectivity, functional connectivity.

Do we see IT after the trip? We know we see IT during the trip pretty well replicated correlation within tense strug effects. Do we see after the trip? Well the answer is we've seen IT in two different depression.

Coho solicited therapy for depression in one study where we look the next day. We saw that kind of residual um effect similar to what you see acutely tes being seen the next day. And then in a subsequent study, we saw IT also three weeks later. So we seen in two independent data sets this decrease in modularity is how we measured its the same thing essentially broadly speaking is the same to an increase in global connectivity, functional connectivity and actually unpublished. We've seen IT in healthy volunteers on a correlational level, not on an absolute change level. But if you look at its relationship to a mental health outcome, and this is an important thing to stress with the depression work, we saw a relationship between the magnitude of that change, the decrease in modulator or increasing global connect and the improvement in symptoms.

severity. So interesting yeah I mean and just stayed a different ways. So um what Robins referring to is when you say modularity is neuroscientists, we think of the the different modular networks of the brain that know I talked to a region of the sellers involved in vision which talks to the visual cortex, which you eventually converses with auditory information, of course.

But there is a separation or modularity of function. This increased connectivity is cross modular in during the trip, but afterwards as well. And you're saying that, that correlate very strongly with the strength of the thai UI c 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 cross talk um between different modules of the brain is so strongly correlated with a positive theraputics come?

We don't know other other than as a relationship. I mean this is this is the thing and we need to be a little careful not to run with IT too far. I mean, there's some things that IT suggests.

I think IT suggests a or flexible mode of brain functioning if you're not getting stuck in modules or the modules on excessive vely cut off from each other, but you see different things with with different presentations. If you were to look at cognition, sharper cognition is actually associated with more modularity. So it's a rule is a little slippery and we need to be careful with that.

I I just again, I forgive me friends, but I think I have friends who are, I would say, her on the spectrum who are a very linear and they're thinking and extremely intelligent in in the kind of classic sense of being able catch IT through hard problems to arrive at a solution.

And then I friends who are just just calling with, they are from the creative communities outside of science that um are very expensive um they see connections between many different things. But you sometimes you have to not all of them, you have to catch their ideas with a butterfly net. And often times, what they're saying doesn't sometimes just doesn't make any sense.

Now they also producing incredible creative works, but to have a conversation with them is anything but a linear experience. They are not random thought generators, but there's a nonlinearity or random to their processing that's distinct from these other folks that i'm describing as on the spectrum. And of course, it's the spectrum. There's some of the whole range in between. Sounds to me like there is some therapeutic value to being able to move along this continuum from the more linear to the non linear.

Is that is that well, I think yeah it's resonating what you're saying it's speaking to my intuition and you know a you could be very party, you know, passing things up, chopping things up like an analytical scientist kind splinter.

As we say in science, you either a lumper or a splitter.

You know the way i'm being very particular about what what went to call something psychiatry you know that kind of passing analytical where thinking you you might associate with a more modular system. You where's the system that's more globally interconnected and open yeah might be more flexible and creative and divergent in the associations. And so and so yes, that speaking to my intuition to how you you're describing IT, and I imagine if you take severe psychopathology severe mental illness like a depression, i've always thought that there's something intuitive about the term itself like a depression in a landscape you know which .

is a musical decision.

physical depression, that is easy to fall into and if you do, it's hard to get out of.

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

do with low mood. You know if you're healthy and inverted commas, you can feel your low mood, your disappointment, but you can spring back.

But someone when you know you can spring back, yeah right? As the suicidal depressive person, or suicide dally depressed person, somehow, at least my understanding there, there is something about the. Extreme depressive states and extreme anxiety states, something my laboratories a bit more familiar with, anxiety, which altered 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. Yeah, kind of a vulnerability to the time domain.

Yeah, yeah. It's so tragic, but that cogniac bias in depression, that everything's hopeless and and that there is no light at the end of the tunnel. yes. So you know, if you were to get stuck in that route and have that bias, then you cut off from other things, other century uh modalities of modules, you know cut off from the world, cut off from other people stuck in your in iraq. And uh so yes, I think we're sharing this intuition that the uh decrease in modularity or an opening up of the the system, the brain could relate to an opening up of the mind that is kind of enduring after the after the psychedelic a dosing session and yeah and and the third replication was to see and healthy and improvement in well being because that healthy we don't look at depression.

So these are people that are healthy walking into the trial. Yeah take suicide and .

twice a well, actually they do. But the first time is one million, which they they don't feel it's surpliced by mo.

yeah.

we have sticky g on their heads to measure their brain waves during each dose and one milligram you see no change. So we I think that you .

microdot or no, i'm just getting that. I I think against the microdot, i've always just been a little bit skeptical based on my conversations with scientists actually doing the work with with psychedelic IT. Seems like the answer keeps coming back.

Two.

two, two, one or two, maybe three. Macro is 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 microbes is just appealing. But again, you know, sense isn't about what we want to believe, it's about what's naturally coming through and what seems to hold up you N A to testing.

Would you say that's right that one or two or three sessions in how how far apart of those typically .

spaced in time and typically one, two, three weeks, uh, across the sites is the way people are doing the the psychiatric therapy during sessions, two sessions, you know, hook kins imperio M Y U. Um it's been a kind of default to we we actually use three in the current anorexia a trials, the side therapy for anne xian, two patients left to to see after a nineteen who gone through the trial, very exciting results. The using .

alleviation of the the obsessive thought about food in willis healthy among yeah .

even improved the weight and the long follow up say .

so critical. I when we did episode on eating disorders and I learned the international nausea, which, by the way, folks, the rates of are not increasing. It's been pretty stable through time despite what said about social media and sea, but interaction, rosa being the most deadly of all psychiatric illnesses, which is a big statement because, you know, manic depression, so called bipolar depression, as a twenty to thirty times that the typical suicide rate, are basically many anorexic people with anorexia A I think is how is is what one says? Not in rexes s but people with anaxibius often die.

Many of them die. Yeah, yeah. So tragic. Soften Young people as well. And similarly with suicide in terms of premature or death.

So the tragedy with psychiatry is so strong and and that so it's it's so rewarding to be doing that trial and to be seeing good results. I have to check myself a little bit that um and reporting on a in this really premising way. And the trial isn't yeah publicly released and published. So it's still ongoing as well. But those .

three three section .

three sessions and I can't say what the dosage is because we still have there is a blinding component um but there are three doing sessions and there let's see now I think there are two weeks apart um and we do the follow up um yes.

i'd like to close out this a description of the of the journey in the trip by extending past the day when people actually take the drug into this um what i've her described as the integration phase you know you have to reintegrate right all this all this increased connectivity during the session hlubi ation insight, anxiety, letting go, maybe revelation, maybe epiphone y okay, great.

At what point is that consolidated meaning um are these patients, subjects and studies having daily conversation with their therapies? Are they journal everyday? And you know, I want to keep in mind that most people are not going to be part of a clinical trial.

And of course, here we're not suggesting what people do or not do, but let's just put in this way where people to a use psychiatric s what is the way that people can maxim on the neuroplasticity and the brain changes in a positive way in the days and weeks afterwards. In other words, how long does this so called integration last? And you know what how far can we take this? I mean, I could imagine that um how often one choosers to think about the insights could also have an impact.

Yeah right because clearly people went to raves. Clearly people did psychiatrically in the sixties. We don't know if clearly people do psychologists now, but we don't have dated 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 into the numbers yet, but again, are incredibly impressive. You know, in upwards of, as I understand, sixty percent or more people getting relief from depression.

Yes, seventy.

seventy percent incredible, especially when compared to the typical the depression treatments and and on. So what is this business of integration? How is IT done .

properly? Yeah, yeah. Gosh, well, how long does that last as well? A lifetime. You know, life is a journey, like a trip is a journey. And there's always work to do, you know, jorn phil says after the extra. Ca, the laundry. Yeah there will be other good ones I forget them um but um yes so the works on going and and and the yeah um but this gives you foot up IT enables people to um do the work more easily and and that's true the classic psychiatrically so so true very true of and a therapy uh for post traumatic stress disorder.

It's really giving you a leg up, making IT easier to do, very, very difficult work, going back to the trauma, trying to digest IT process IT integrate IT um so it's such an essential component of the treatment model, but one has to be realistic as well. So you know by saying our integration last a lifetime, well people delivering a service can be there for a lifetime. So um what's the answer? The 嗯 and people are wrestling with that issue right now。 Um and I I think one of the solutions might be that it's innocence on you uh to a point you know the therapy tic team can treat you to a point and then IT becomes what you might call practice in a similar way that meditation is a practice is something that you have to keep up and if IT slips then things could slip and and that's the way IT is all you have a and another psychiatric treatment.

You know so people have even used this term of practice in relation to psychiatrically whereas a PC delic practice like there's you know a meditation practice, but amusing meditation um intentionally here because I actually think that um meditation practice um spiritual practice, elements of spiritual practice could be a very important compliment to psychiatric therapy ah and I think it's probably doing something similar in terms of promoting an ability to sit with uh, a former colleague of mine that is quite well in relation to psychiatric therapy versus chronic pharmacotherapy or like accessory being on the all the time this psychological therapy allow you to sit with rather than sit on. I think that's quite good. Um yeah so you know the meditation, the mindfulness um ability to yes be present counted but also present cents in accepting. So if things come up you can watch the process and then let go .

that holy grail of of mindfulness you know you know awareness without reactivity respond. I, I, I group in the the area, you hear this language, right? And i'm not being disparate ging. This, my friends that are on the board of isoline and worked down there, know, and i've gone there and you know, and yet you hear these terms right be responsive, not reactive, which to a neuroscientists is like grades on me which probably just means I have issues but um and surely I do but you know elisia what does that mean right? It's saying like go to be the observer but not be drawn into the experts.

And again, I don't want to be overly reductionist, but what I find so compelling about the emerging data is that really is data on psychic alex as treatments for depression and trauma, namely suicide ban and md ma, is that IT really seems to allow people this space that that is so commonly throw around, you know, giving space between stimulus and reaction and virtual Frankl. Talk about this. But, you know, i've been reading a wonderful book called the prince of medicine.

Good dates back to the of medicine, very dense book, talking about this stuff. And think about this stuff for thousands of years, psychedelics seem to give people access to that Better version of self, which is remarkable. So 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 publish an entire issue about psychiatrically with how kadee words m dma illusive and with the appropriate cautionary notes in there. But clearly, times are changing.

Speaking of which, I know you're doing a trial on first time use of psychodeviant s. What inspired that and what are you observing? And as you tell us that, please give us a few of the key on to us.

What's the dose um hold? Are these subjects I assume that the men and women, are they suffering from depression or not? Well, what's the landscape of that study? And I I realized this is still early days of the study or maybe it's close to completion.

It's not yet published, however, because it's not publish, its not submitted. IT is completed. So this was one another one of our code studies, in a sense, meaning cover hit. And we had to finish the study and IT was hard to finish the study because the cover that was true of our solid interview versus as the telegram lexus o trial um which is published new english of medicine. But the was twenty that paper.

by the way, folks will provide a link to in the showing te captions as well as some of Robin's other papers I think twenty twenty two new england journal papers really fabulous given its the different dosages and the comparison to essentially what is micro dosing and the comparison to the alia yeah that's interesting .

that you you link the way we get small dices of solar de into micro dicing. We didn't think of IT that way.

We thought that was just a unnecessary plus ibo for the big, big days, the twenty five million that yeah and so that we could say to everyone we're giving you sale IDE and and not be lying yeah for those who got telegram lex approve for six weeks, they they got a very, very low dose of sale, but allowed us to standardized all the psychotherapy and so on. But the the other study that you're referring to was in healthy, healthy volunteers. Middle age average I think was forty.

So not your typical students study that so often the case in psychology research, you know all all the other crat and a volunteering for a study. Uh so this is some uh more more than age range. And also I think there was an equal proportion of male and female. All the staff actually were female, which the staff were very proud of them.

although IT produces its own potential confounding right to have all one one sex of of .

staff possibly. Yeah I did a good job in the sense that um we saw significant improvements in well being at the end of the trial. So let me describe the design.

IT was a repeated measures design meaning people come in, you collect your baseline data and do a brain scan and you give people um a placebo. We gave people a placably actually let me remind a little bit everyone's healthy volunteers midday age never taken a psychiatric in their life. None of them entirely in a fresh verdon.

People coming in and uh and the plan is to give them their first of a psychiatric experience. So that's what we did in the study. But to do IT, we have this repeater measures design where that i'll first get a proc bow and we have the proceed by so the weekend do all the procedures, all the therapy or the music listening but not give a warping dose of salicylic.

Again we gave them a proceed to solide in more milligram. We stick E G uh headsets on during the experience to record the brain activity um from the scale of the isolating electrical ectivity. And we do the MRI scanning um before enough 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 the study. So the the short story is the all of the changes that we saw, both psychologically and neurobiological ally was seen with the twenty five milgram IT, all happened with that big wapping dose. And what did we see where we did see significant improvements in psychological well being.

We saw what equally entropic brain effects, which is actually formally quite accurate, we see an increase in the informational complexity of ongoing brain activity recorded with the E. J. On the day save soichi ban.

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 the subjective effects are the bigger trip, the bigger this entropic brain effects.

Now pretty well replicated finding um but then the M R E M R I and think deep into the brain was probably our most exciting results 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, 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 we sort of limited our search base to really thick tracks, really thick fibers and the fibers that came through as changing the ones that traveled between the prefrontal cortex and and the Thomas in the stratum. There were two tracks, two prefrontal tracks that changed and they changed in the direction of the decreased in x deficience ity, which um could be interpreted as tract integrity, where a decrease would be an increase in tractive integrity. IT is something that you see in the developing brain that actually divisive ity decreases as the brain goes from being a baby to being an adult exil deficience ity goes down and in an aging and path, logic of aging, x deficience ity 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, if I understand correctly, and i'm perfectly be happy to be wrong by the way, that this decrease and exile diversification is translates to a higher fidelity of communication between the prefrontal cortex and the dominus and trade m, as opposed to less.

And your description of this is somewhat like the the transition from babyhood childhood to adult speaks to the same where we know that there is 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. Is that .

right ish? Because the the change was anatomically um 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 are synchronous between regions.

And if they are, we say they're functionally connected and we inferred that they are talking to each other because they go open down in synchro. But when IT comes the anatomy, we're talking about the you know material staff and uh um so we're seeing the fibers in a property of the fibers change um at least that's what we think. And recently we had an independent person come in and we analyzed the data because you know one of these things, incredible finding required in a credible evidence, really strong evidence and and I would say the evidence of the moments won't study.

So we need to be cautious on that. But we did we an analyze IT and use this um correction procedure, free water correction to be more sure that IT was a changing in the actual microstructure rather than something to do with the extra cellular space, the the water surrounding the fibers. And IT came through IT. In fact, the the change was strengthened by doing this correction step.

These are this is neural plasticity as the consequence of one first session with twenty five milligrams of silver.

Yeah, yeah. So we're excited. And and the different in the second analysts coming in um wasn't sure he believed IT and then SHE you know I thought this correction technique might kind of kill the result and then he came through and and she's like, okay, now i'm excited too.

So we'll see. We don't know what that means. What what does that mean? functionality? We don't know. How did the people change? While psychologically, as I said, uh, well being improved, we did look at their cognition.

And we is the a cogging tive flexibility paradise that looks at people's ability to notice a rule change and then flexibly adapt their behavior based on noticing this rule change. And people improved after the twenty five milgram, and didn't significantly improve after the policy motos. There weren't correlations with the the D.

T, I change, the the cabling change and the psychological outcomes. But you know, with these studies and smaller samples, zed, you don't always see those correlations come through. Um so it's something we don't know what that means, but it's 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 in Normal arrow development into adulthood. Very.

very exciting and intriguing. And I appreciate that you highlighted that is just one study, although from everything you said, that sounds like been done with immense rigor. So we will eagerly await the publication of that study. And as we can prove 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 solicitation on for the treatment of fibre. mil. Ja, i'm intrigued by fiber melcher because I have a good friend who also, I won't reveal who he is and I know it's not mean, this isn't that I have a friend thing who also is a scientist who 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 um the standard medical community has um largely ignored fibre biog a um and that for many years IT was kind of lumped with things like chronic fatigue syndrome and other um so called again so called i'm not saying this but people offer in for to these oh it's psychosis tic that's all in your head wich as a neuroscientist is a ridiculous statement to hear because it's all in your head your brain is in your head after oil your physiology and psychology are influencing each other of course and and the world is starting to appreciate that more but first of all. Maybe you could tell people what fired alga is what inspired you to do a study on fiber malaga using sliced and of all things because that's surprising to me and um if you are allowed to or if you have access to the data um in mind, share with us a little bit about what you're discovering and in that study.

sure. Yeah happy too. So again, solo sob therapy and the population is fibro melodious and drome. So this is people presenting with the 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 and for that reason, it's hard to to know what that is and that's why it's been a controversial space in medicine and it's been yeah it's had that charge thrown at IT that maybe a psychosis tic and just see your point is anything ever you know independent of of the mind anyway? But this is actually a fascinating space for how, in a subjective experience, lived experience, and the mind can influence the body, because that some really interesting literature around the etiology, like the how the pain has come about, in a sense, like what caused the pain? What's the story? And I head 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 um how um ah that can relate to issues, relate to inflation tion and how that can express into things like viBrant melodist syndrome.

I just said be very careful there because if you go in with an assumption that there's some berry trauma, for example, and as a whole other side of psychology sis that massively tripped up around false memory and so on. And so please don't hold prior assumptions that you're gonna uncover um very trauma in every case. Now the team are treated, I think eight people and it's going IT is going very well again.

I just wanna be careful with how I describe IT to you know to manage expectations and not get too Carried away. But I checking with a team every weekend, there's still based in london doing the work. And 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 where you have the E G. Cap on in the sessions like in the healthy volunteers that you beat this time now taking into a clinical population. And so they're .

in the they're wearing in I mask under the influence of twenty five milligrams of solicited on. Most of them probably have not done Sullivan before. So it's a little bit like the first time study in some sense, they have fired maler that's dibbled ating in some way, don't want IT, obviously. And during the session, are they thinking about their pain? Are they being told to think about their pain?

They're being told to think about the pain in in fact um as I understand that while there is a therapist model around the acceptance of the pain IT isn't and unlike some of the P T S D work you are encouraging them to focus on you the index trauma and then you work through IT and try and digest IT.

We don't do that with the pain so the paints there um but there isn't an invitation to focus on IT and that's probably one of the differences with classics psychodeviant therapy versus M D A therapy. Arguably M D A therapies more like speak closer to traditional talk therapy, where there is more dialogue. People are able to talk .

on md ma um in the md ma trials. Do you know whether or not they used I masks or because this seems to be an important distinction between, as you described, the therapeutic trip versus the trip that one does are going into the woods and taking taking self ibn in the woods or at a party or um while staring at a poster or or a or a leaf um again, i'm not trying to trivialize these experiences. I mean, obviously they can be profound but so i'm told but the md ma trials seem to involve, as you said, more more directed dialogue um and sometimes even kind of apathy 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. Um so do you know if they put I masks on people during the party?

Sure they have the I masks there because .

a lot of the m dma work and I was part of an M D M A trial. Um IT was um as I understand gear tard developing because it's an impatient en empathy toward the self .

yeah I pretty sure they have the I masks there but they probably and is a great question because you formally test this IT probably don't use them as much thing is with the classic psychiatrically, if you're looking at your guides, your facilitators, ors and their faces are .

melting on md ma. You just might really start to feel .

more connected yeah might especially yeah and and yeah there's that that fascinating effect of loving you know the people that you're with and so yeah I imagine they talk more and use the ice shades less and IT is more interpersonal or rather than like interperting or going inside they do is a fascinating terminology that some people are critiqued but IT is a very interesting uh, phenomenon and and is this notion of the anaya they use that that language a lot.

It's been critical because IT sounds very suggestive, you know and that's probably one of the vehicles here driving the therapist process is suggestion, I think have to be honest about that um um but uh so when they go inside, that's another term that we use very much in the classic psychiatric therapy work. You go inside, you know, you put the ice shades on and people are encouraged to go inside, you know. But when they do that in the N D, maybe especially, they might be told, explicit and listen to the anaya.

And I am not kind of language, so you could see how A A sync or a skeptic could come in and and see that some kind of like suggestive prime or passing. I think they they have a point. Skeptics often do.

But I I don't think this is uh, all of the story and is briefly because it's an interesting point. And speaking to that point a bit, in our solar eban therapy versus as taliban trial, we measured pretrial expectancy and we did IT for both conditions. So you know what kind of improvement do you expect with the lexapro the us.

To telegram at the end of the trial? And what kind of improvement if you go into the solar ebon ARM and get a big two big doses of solar yb on what kind of improvement teething you see in in in that? Um and of course, he was a coin flip as to what ARM people went into and there was no cross over um and what we found was IT was true that we had a um a sample bias.

So most people had higher expectations on average. There were higher expectations for solar ibn and its efficacy y or effectiveness versus the S S arrive lexapro um however, when we looked at the correlation or the predictive relationship between pretrial expectancy and response, we saw the pretrial expectancy for the S A telegram predicted response to as a telegram across specially every single measure, all these different measures of depression and well being. And and I think none of the scales, and pretty sure I was none of about twelve or so mental health rating scales was their relationship between press trial expectancy.

Even though IT was high, IT didn't predict pretrial expectancy, didn't predict response to the solo therapy, say that was a bit of a you know smash on ahead for the idea that the classic psychology therapy is some kind of policy by response and I think it's so important to address that question um because if IT doesn't come through as IT didn't is IT didn't come through, then IT opens up even more intrigue about well, what is IT then if it's not just a policy by response or super policy by response. Like an amplification of the policy response, then there must be something else. And how intriguing IT has a direct therapy to action.

IT must be something. And we don't yet know what IT is. I talked about the the residual in increasing global connectivity. That's one possibility. But the truth is we're just scratching the surface and .

yet the therapeutic outcomes are again just so more marvelously impressive. Um i'm curious to why as well there are that many labs, but the the laboratories that are focused on classic psychiatrically for the treatment of depression and and now as you mention, promising results for action and fibre biology as well, although preliminary, very promising.

A why the lack of attention toward A L S um is IT that the L C trips are just too long? Is IT that they are quality timely different? Um are there any data on um non microdot of elliston here? I want to be very careful because I learned through by interactions on social media that this term microdot is very misleading and in some cases can be dangerous ly miss leading because as you mentioned earlier, the effective psychiatric dos, or the affect a meaning that can induce a real trip with illustrations at at A A of L S D, is actually in the micro o gram range.

So some people hear micro dos and they think microgram of L D is a microgram is a microdot, when in fact, in microdot, lsd can be measured in micrograms, right? So this is where you know, in the absence of scientific training, people can really go go a straight or even in just a lack of understanding of the metric system. And since now you're yeah you're a recent rival to do yes, fortunate for us.

Sorry, england's loss is is the U S. Has gained by a robbin's lab move from from england to the united states recently so score one for us. Um but why isn't there more use of SSD in these trials?

I think if IT probably is the duration of the trip, but used to be stigma um and IT was easier to get your side aside and study through because others were they were getting that true.

So there was still like to france volunteer in eric switch are learned and then rain griffis coming along in doing this solar ivan work at hopkins so you could appeal to that presidents and say what we're doing IT over there, you know can we not do IT in in little? Um that's how IT work for us. We did actually go on and doing A S D study once we kind of lay the foundations um for doing this kind of work.

And IT was a brain imaging study, a really extensive one actually where we use both MRI in another modality called M G sort of super E G in a sense. But you know, why didn't we? Why didn't that turn our heads to think goal? Should we not be doing our trials with our it's does have something to do with the pragmatics, like a study day with solar de, and is long .

enough to four to six hour.

Ask the people in the lab and until eight hours post those with personally, I think could be quite excessive, especially if it's a low dose. You know if you have that in the proceed by condition as well, IT becomes long in practical.

but scientists are not paid nearly enough to warrant the there's no such thing as over time in for the graduate .

student in postdoc, often you know more to members that are doing that really hard work.

Uh, I was describe 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 electrophilic gy, so he would run experiments, no joke folks, three to five day experiments, sleeping in bouts of two hours here, there, in a dark room with a bunch of equipment and recordings.

So these are long, long, acute phylogeny election philological recovery. So, ah, no, no scientist does IT for the money. I promise you that there is money in farma.

There is not money in uh, personal income um is not lucrative if the basic scientists. So yes, L D is what? Anywhere from eight to fifteen hours?

Something like this would be a little long. You would worried if was still tripping at that time, maybe with a really big time. But yeah eight hours plus and those dependent, yes, it's a bigger day, it's a longer experience.

But you know if you are gonna say, you know ten A M in the morning, which is more or less how he often goes, then at six P M, still feeling the effects, and then how long you wait now to can close things out before they can go home, even with solar. Yvan, you have people still at work into the evening, and the staff were always there later, of course, because they got to a pack up. And yes, so these are long days and IT and it's it's too makes .

sense practical constraints. I learned from a recent guest on this podcast um uh that we recorded with a doctor's setch an panda was a colleague and when I was done at the sole constitute is a pioneer.

A lot of the studies on so called internet and in that the reason the internet in that that the eating period in these studies in animals are now on humans is eight hours that are feeding window in these cases because the graduates student was going to otherwise lose their relationship because they're significant. Others says, list, you can be in the lab for twelve hours. That meant some hours before the experiment than eight hours and then some hours afterward, but you can't stay in their longer.

And many people use the eight hour feeding window as a consequence. So the science has to exist in and be Carried out in real world frame. Yeah mtm is a little bit um a little bit shorter. Write is about a .

is similar to that in the maps work they read after a certain booter a booster so there is that um and now people are thinking, well, even the solar de de in 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 bridge the experience, make IT shorter and get away with IT and get get similar kind of therapies outcome. So there's a lot of interest in .

that direction. They ask about sorry to help, but I want to make sure don't forget to ask about combination suicide md ma therapies the reason I ask about this is and here truly not me but I know people who um do self administer combination Sullivan and M D M A um I think of this right I think it's called a happy flip. There's another one that evolves else too.

Again, i'm not suggesting people do these kind of drug combination products. But the way was described to me was that the silica ban because it's so certain erga sometimes can be not a downer but can have a bit of a kind of a kind of a monkey field to IT some real deep introspection, sometimes in the the darker realms of ones psyche. Depressive thoughts at set a, not the initial stays that way throughout the trip, but that the m dma, because IT has a very strongly search error, but also dopa energia.

I mean, so if this has an infect mine component, a cocaine, like in fact um if you have ever seen to want to md ma, their pupils are about the size of of quarters for reason there you know um extremely extremely onic sal compared to executive which by the way would construct the pupils. So they described the use of md, made a kind of baLance out the kind of affect component of IT. Um what your thoughts on combination solicit an M D M A does this hold any therapy potential? This is obviously a backyard chemistry um in the sense that people are what you know cowboy the stuff on their own which you again I don't really recommend. I'd like to see the science go first but I understand this is how IT works in the real world yeah are your thoughts on combining compound yes.

I guess cowboys in recreational context, but also underground .

therapists do work with this combat. People with this stuff i'm talking about, there are thousands now of therapies offer second tic therapies illegally really because it's not legal, at least not in the us, to possess her cell, but that are doing this. Yeah so that's really why .

I asked yeah yeah and you know I think there's something to be said for when has be careful with this as a scientist? But you know if they're doing IT, are they using some kind of rol an error? The same is true, of course, with the you know longer history of psychiatric plan medicine using by plants.

We include the fun guy as well. So in the extended sense, plants, you know, there will have been try an era there. IT might not be a systematic as the sense we do today, but maybe there's been a learning process and maybe what they do they've come to because they have found IT works.

So by that principle, i'm interested in that combination. And whether IT does offer some advantages may be uncertain. Patient, one of the past terms in medicine these days is precision medicine, a procedure medicine and personalize medicine. So maybe there are certain cases where you know introducing um say solar de an after the M D M A or the other way round could offer some advantages and the differences are interesting you know soichi ban get you to deep places, maybe you know the corner of your suffering and and major life experiences complexes, the causeway link to whatever the pathology that you're presenting with um but you can do IT sometimes quite aggressively and I and if IT say posta matic stress disorder IT can be overwhelming and you can fight IT and really it's that is the you know the resistance is really chAllenged and they fight back and the therapy at breakthrough and the progress isn't happening because you've agitated the defense mechanisms. Where's what m the office is something arguably more directionally reliable in terms of in terms of the baLance, like it's more directionally positive generally and M D, M, A experience .

yeah to be quite blunt. I mean but one of the concerns I I had with mda, i've never done IT recreation. I have had not and have not never done IT recreational.

But when IT was done in this, the apex tic setting, I realized because there was a music on at the beginning, I I actually asked him to turn IT off, because I realized that the 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 know for. And i'm glad that they did turn the music off, because the moment they did, I was able to drop in within the ms. To this the 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 m dma is that it's such an impatience en that one could start to you could go down any number of different rabbit holes. Yeah.

yeah. But but it's also it's a strength because you well, you know the classics like soichi bing can take you there very reliably, but maybe a bit aggressively. M, D, A makes IT easier to go there.

And and that's its strength. And that's why the marriage of P S D. And is a is a good combo.

IT works because you are gonna there in a sense. You have to to really make the therapy progress. You're gonna have to go back there.

Um but we we're gna set IT up so that you can go back there and feel a safer, more trusting and be able to go back there. Where is you've never otherwise be able to go back there without you associating or having you know horrible flashbacks and so on. So that's the strength that IT offers. I guess the limitation would be that maybe he doesn't take you as deep as the uh classic psychodeviant xin. I tend to think i'm based on this one that there's a kind of onest y to the classics and that IT is IT is hell as well as heaven, you know and that's the psyche IT is in all roses I I really appreciate that .

you bring that up because I think that there's such a fear of uh uh so called bad trips. There's such a fear of in non psychic tes to um to avoid the painful and everything everything we know from trauma and the treatment of trauma. And we've had several guests on here. My close college close close college gets sanford, doctor David, speaker, associate chairs, psychiatrists, clinical hipness sts.

Amazing amazing human being and scientists and clinicians as as really just you 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 has experienced there is no other real way as so I really appreciate that you're saying that the classic psychiatrically may offer the the with a very strong nudge perhaps the opportunity to get into the the uncomfortable in a way that md ma some non classical psychodeviant s perhaps do not. We are talking about time frames or duration of trips and these different compounds and how they differ and how they are similar. Um i'd love you to educate me on d mt and some of the words that you're doing with d mt.

a. My understanding is that it's a very brief trip minutes. Um people I know who've done this again, they're peut ally actually. Um just point to one very exciting, I think, group and initiative, which is the veteran solutions initiative, which is a group this is that Carried out in mexico but in conjunction with laboratories at stanford and elsewhere who are evaluating the neural changes.

And this involves I begin, which is ebola, which is a very long duration psychiatry, twenty two hours or more, followed by A, I think, one or two doses of d mt. This is for veterans with to deal with any number of issues, 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 d mt, almost across the board was, quote here, i'm just pulling quotes, right? Anethe data, the most profound experience of my entire life, even greater than the birth of my children. Quote, like being attached to the shock wave of an adam bomb.

Quote, there is no way I would do another dose, because the first one was so unbelievable. Interesting, by the way. Think most of us, including me, we think, why went you wanted do IT again then? But this idea that that was just beyond anything.

So these are significant excuse. These are significant statements coming from individuals who have existed at the extremes of human experience. To begin with, right? These are so called tear.

one. Operators within the special Operations who exit and mayor may not have trauma, but d mt, sounds like a big deal, short duration, really big deal. What do we know about its chemistry? What do we know about how it's 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 it's a rocket ship with. If the solar ibn is like a ship leaving port, then yeah this is this is a rocketship craziness. Is is IT .

serotonin two a IT is.

yeah so IT is a classic psychodeviant tes, the direct agonies, the direct stimulator of the serotonin to a recept. Ah it's a an order of magnet de less potent than but potent. Ces is a funny thing because those dependent so that doesn't mean that the experience with emt is less than that of soybeans, just that you give more of the drug but has not matched by its stickiness for the serotonin.

A recept, which is this kind of golden rule in in psychiatric science, is that IT was discovered in the middle nine hundred and eighty. This tight relationship between the affinity or the stickers of the binding potential of a psychiatric for the two a receptor, in particular serotonin two a, and its potency, and the sticky of the drug, and more potent. So, L, S, really sticky, very, very poor.

You only need those tiny microgram doses. So D, M, T, bites of minutes is a little less potem. But by its effects, when you give a standard dose, it's just in it's just wild and d mt because there's another combin called five methods I D mt, which is a bit different pharma logically and subjectively in similar in terms of its connections. It's another rocket ship, both compounds in the wild, so to speak. Um smoked often T M T and five M O people are waking both actually now um there ate vate pens had have been developed for people to administrate minister this but more traditionally it's been a smoking thing.

This is clinically, not recreationally or both both.

Now you ming, you know, underground practice is using the way pants they like them because people titre the dosage, they get a feel for what IT is to be going into the state so that they feel like can let go and go into IT. But and actually, I think some of the veterans work might be giving, five years after the eye became an phenomenology ics, if there's a difference between D M T and five A M O. People might put IT on five 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 immersion and everything ah.

But we could just talk about ego dissolution for a second because it's such a sticky, interesting idea 啊。 I can take a step back as a neuroscientist and and say, okay, ego dissolution, this idea that the that know from a very early age we have a concept of self, and that know I wake up every morning and I know i'm me and not somebody else the same and most people do the same, I would hope, but 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, a elimination of the of the idea that things stop and start and stop between us and everything else, almost like, you know, and kind of a here, i'm not trying to sound philosophical or metaphysical, but there there sort of the molecular continuity of of life, right, or all that IT all just little, little bits. It's 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 up a coffee. But um but you know what is the the what is the power of ego dissolution? Is that the idea that we that we like 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 used for way to go through life.

You know, to think that we're not as as 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 two a activation causes? That's remarkable.

Yeah great questions. I mean, what what is IT? Um you will lead to IT with the start stop I think you know because you could define IT by boundaries in a sense what is what isn't me a is as valid here is isn't you know a developing sense of what is me that a child develops at whatever age um and um so a major characteristic of the ego dissolution experience rather than just a negative thing going away. My sense of self going away is is the positive oh, now I feel interconnected with other people in the world at large and I realize you know that there is that molecular continuity and actually that's a ground truth. And or maybe the ego thing is somewhat elusive or at least the construction of my mind.

And indeed, IT is right.

Well, IT is yes. I mean, there's no translator ism about that is just like logic.

I think about IT a little bit like family and we all know what immediate family is but you know serve like forgive me for interrupting myself I do IT all the time anyway um when I teach her anatomy, you know some clevers 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. yes. And so you really just have to decide where you draw the boundaries between.

Are the mother? You say the brain? Just one big macro o module? yes. 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 nerve system extends to both, of course.

So as the same could be said of family like we're related, right, not just by virtual fact that were human beings that we did our geneology ical charge, we would find a convergence at at some point here. 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, is that that's a game too. And so IT is just a construct yeah.

mean, that is a fun game. You know, where he draw the line and went to pass and went to collapse is is also a classic consideration in science. Went to pass .

vers litter.

really yeah it's the us is question like why do psychiatrically do IT? And there we think psychic delicate do IT because the target receptors, at least you like classic psychiatric s do IT and that's important to stress. So and that may doesn't really do IT in the same way. Yeah that's the Better. My experience .

with M D M A is that it's such a strong pathogen um and and that I can do cause empathy for others yeah certainly you could imagine situations where one in md a journey and afterwards says, you know these these my oppressors, you know the people that harm to me they and here i'm not referring my experience, but they did the best with what they have actually have empathy for them. Forgiveness yeah, but also for oneself that there's in a empathy for self. I know I said this earlier that is very hard for most people to access. Perhaps it's not the arcesius out they are listening theyll be like of course empathy for ourself but everyone else I think um all the other healthy people or the healthy people other than nurses and not picking on nurses, I have to imagine they suffer to in fact I think that's the root of their nurses ism um that empathy for self is not something that comes reflexively for most people and here i'm not about self love, 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. I think that's the way I kind of conceptualize yeah.

yeah. But I mean, drugs offer of a great, they offer great, they are great scientific tools for tackling this question. What does he go to solution? And why do drugs modulator? And what does that tell you about the brain? You know, because other drugs like cocaine releasing more of a different europe transmitter, uh, dopamine more than serotonin, the opposite is the case with m dma is more of an an ego inflating, right?

H absolutely. People become a hyper linear, hyper linked to their own desires and wishes. And future outcomes become an obsession. It's the stuff of kind of american cycle and the kind of classes and stereotypes of the the the eighties.

uh uh, cocaine culture. Yeah yeah. We did a study once actually looking at those dependent relationship with ego inflation on one, access to ego dissolution on the other, and saw that IT just massively passed or differentiated between cocaine .

and and psychiatric s it's .

is the case with this at the imaging to explain .

how how cocaine does that.

That would be a great study. Yeah, great.

We should do that was coming up. I got twelve months of coming up. I'm going to show up in your .

lab yeah that's a really good one if if it's right finding the thread on on White psychiatrically and you go to solution, we do know some things or you know we have some hypotheses. Season is the the target receptor is a serotonin, a recept, as the classic psychiatrically hit are heavily expressed in what these days I like to call recent brain. Because evolutionary, 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 same meaco or chip to human, it's the very same map that you'll find the two a receptions in. Um so that's the target. It's and it's just easy to think that h that could be the egoi brain, you know and and the classic cycle that it's come in, they kind of they grambling up the activity that's the entropic brain action and in terms of you know the start stop the boundaries um that entropic action so that spreads out the system um IT doesn't shut IT off IT sort of spreads IT out you know I um the solution yeah and you know the you were talking about the head space as well so that fits if it's you know if it's more capac ous sort of fits.

The big qualifier with psychotic c therapy that the people rightly bring up is IT doesn't last as the paradox of IT the paradox of you go to solution so the ego might go away during the trip, and you have these profound insights about the molecular continuity and how we're all warn and interconnected. And then you come down, and however, long later, you know, the eagle comes back, but maybe the vengeance, and sadly, you know, things can go right when people haven't done the work, haven't done the integration work and maybe ego defenses come back in E. N. A. And it's not it's not a pretty picture.

Um how often do you see that in the the trials that you do? What percentage of the the of people coming through? What do you think end up with worse than they they were before the the trial?

It's very rare in the truth that we've done. Yeah but you see defences come back. So you you do see people relax. That's more you you pushing out to like three months plus in something like treatment resistant depression, that's more the rule than the exception. Sadly, people relax if their histories ah you know histories of china ic depression then while you might give them A A window wellness sadly doesn't last has not to say that IT doesn't ever last IT does and we have people who were in our first treatment resistance depression trial who were well to my knowledge today back at work doing fantastically well. But sadly, the majority of of relapse, to my knowledge.

and need to do more psychology. Ney, well.

they because it's illegal. That's been a really difficult situation that we've been up against. Do a try where all of a sudden is schedule on drug, becomes a medicine in the trial. Listen experimental medicine, we give the treatment IT works fantastically ally well gives people a remission that they've never really had um for however long. And and then the trailers and they denied that treatment and were still if they were to have that treatment, they would be committing a crime, sort of a sick joke in a way. But that's that's a situation .

that we've been in. And that's a perfect segway for what I want to talk about now, which is what is the current state of legality. In terms of the progression towards legality, i'd also like to touch on the role of, as just say, incoming big farma.

There are a lot of start up companies now trying to capitalize these discoveries that you and others have made you. The landscape out there is very unclear to me. Um 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 grass roots, but at the ground level.

I look to laboratories like yours, Matthew Johnson s rolling griffis, some laboratories at stanford knowler Williams laboratories doing, studying the effects of psychiatrically in human beings, so not animal models in terms of their clinical application for the treatment of depression and a no fibre, my logia trauma, let's lump of M D M A in there as well, assuming that IT all works an equivalent way at the level of kind of wear. The legislature is taking things, okay. So labs using government money, philanthropy, eeta.

Then they are the they of the therapist out there that are accessing what we believe our clean sources of m dma. Solicit an elastic to do this. They are doing IT illegally. This is in the U S.

Or other western new rope an countries because obviously it's going to defer by country um 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 an experimenting hippy flips and combination drugs and cademy. And it's a abilities academy out for IT right now because it's legal. But there's that then there's the um I don't want to say it's a recreational slash open market, black market.

And here I want to raise a flag to the fact that A A dr. Peter T. A. Did a terrific podcast on this recently in his own podcast, the drive, the fact that fatal lacing with fantine's now showing up in M D, M A and psychiatric that are purchased on the streets of serious caution to those getting IT from uncertain sources. And and then you've got farmer. 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 been used in a clinical trial. Selling in a possing IT can get you charged with a crime ranging from, I don't want to say because I don't know, but up to files right years in prison okay.

so I take IT through airports.

can not get caught with IT don't buy IT don't sell IT kind of think so where are we going from that picture of the celilo? S, I know things are in clinical trials now. Most people, including myself, are not familiar with out the different phases relate to the proximity to legality.

Could you just kind give us the landscape in touch on how long you think IT will be before the people that come through your trials could then go get a proscription for solicit van or potentially buy IT without the risk from a reliable source, one would hope, but without the risk of getting thrown in jail? I 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 solicit an is decriminalized in oakland, but that's not the same as being legal. So what is going .

on out there .

was so much I have just feel free to answer.

Well, oakland of funny one. I I live close to icon. There are head shops in oakland. Um I the might be selling cannabis and you know cannabis related party ili that are selling mushrooms as well.

Suicide de and mushrooms and thing yei fy, I haven't purchased them but i've gone in and can check IT out like .

what's gone on here yeah yeah yeah so in a uh the police aren't going to prioritize um that activity the purchasing of of those mushrooms as a crime now in oakland because of the decriminalizing. So those had jobs 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 lets see whether they get shut down. They probably well, I don't know there's there's a church you know in in ocean that sort of say that they're selling and is part of religious rights that they're using that church model as a loophole.

You know the way that native americans can use peyote and they have a more genuine OK, I think because there is a history that um etra ic on a pig back on that anyway that's that's sort of you close to where we are right now. But um federally, which is really the major inflection point, is the fda um and license singing of psychiatrically as medicines to be legally prescribed across the country to cross the U S. And beyond.

Um that is close because the key um phase there are different phases of class and the key to know about its phase three a phase three trials and licensing trials, if their success will typically have to do at least two successful ones show the results to the regulators who are the F, D. A, the medicine regulators, and say, is this good enough now for you to give me a license so that I can sell um and provide this medicine that we've demonstrated this medicine um so that work has been done with M D M A therapy postal matic stressed disorder maps have let that work and done two face 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 sixty seven percent remission rates.

And long term, I understanding, is some of those remission rates for trauma years, which is different than what you're describing for silicon band, where people might need ongoing dosing.

That's true. yeah. yeah.

But of course, just for trauma in those trials, my understanding is those M B M A trials were not focused on depression.

Yes yes, focused on on the trauma. So that's something because the that data is being fall now, to my knowledge, like as we speak. And um they're anticipating a decision maybe this year with roll out happening as early as next year. I mean that sort of best case, I think .

could ask you when you say roll out whose work in IT to appropriate term for M D M A so called rolling, about twenty percent of my audience, maybe fifty will will understand that not funny joke that I made who's going to roll IT out is this where would one get the M A that the clean source of N D M A meaning not least with val not laced with mEthanol to mean um not undergone any chemical controversial some other drug which can happen with extended shelf life is at there are people going to go to their psychic atrix to get M D M A and who's going to be providing IT is not going to be some big major farmer. Uh this seems like a serious set of issues.

IT is and I don't have all the answers I I do know that maps would be providing because theyve done the work and they have set themselves up in a sense to potentially become the provider. Um whether is a farmer company, which is the big question they're story with the moment, it's very expensive to become a farmer company.

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 river culture party drug. They were the ones that spotted the therapeutic potential that I mean, we knew there were theraputics tenant, al, based on work going back many decades, but pointed to them. And I think I think in my opinion, they should have the agency to make those .

decision yeah and is a really such a remarkable thing that's been achieved. And I think we've done IT all on philanthropic donations, I think so. Yeah so there there is this yeah big question mark in the F, D, A are also asking questions about um to to your question, you know who who can provide this because in the face three working up until this point has been a maps training, a map therapy training and you have to do this formal training um in order to to be a practice within the trials but now there's a question from the fda whether that maps training can be the training that a clinton has to have to now be a provider. And when I say roll out is like um offering, this is a service essentially.

And so where would the referral come from? That's a good question that are not hundred percent on the answer, whether IT would have to come from a psychic st or whether someone's um so the general physician could do that referral. But they will be going to a provider who is license and certified and will have done some training and 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 clinton who provides. So I imagine they will have to be a mental help professional. I don't think they would have to necessarily be a psychosis. They could be a think a clinical psychologist for all the other things. I think without question, there would have to be a physician present or at least within ready access in case of an emergency.

especially with M D M A because of the a prepense for cardiac issues ah, because of the. Properties and where is solved. And in terms of the phase trials is that in face two face .

three it's in face three the solar ban therapy work being done for treatment resistance depression by a company called camps uh those trials um which are always multi sight. So there's always a bunch of teams or labs in a sense um geographically spread out that a reach contributing to data that then gets mass together and is then submitted as part of the face three trial results. So let's happening with compass right now.

It's such as sub therapy for treatment resistant depression. Those trials have just started. And I think the earliest estimate that I heard in a in a journalist article was because I I think camps would say, or they wouldn't say publicly, something like twenty, twenty six.

twenty six. wow. So m dma is is a head.

So oh yeah, yes, quite a few years I had and it's more of a not a certainty but is very, very strong position with M D, M. A. Where's the work only just begun with with solar de and in terms of the face three trials, but then you have this other situation over, like however many psychiatric research chances there are now across the globe was nice to and we had the first one in london in two and nineteen. First one in twenty twenty is twenty twenty three now.

And I don't know how many there are but so much has happened in such a small space of time um yes but you know all these different indications i've been able to tell you about an ex ia and fibre mildest 的 trying to do trial uh with a colleague of mine and you see itself in mEthanol t minus disorder a he's got a troll going on in parkinson's disease a and chronic low backpack and bipolar disorder， I mean that so much going on. O C D almost the full game of psychiatric disorders um not schizophrenia to my knowledge um are being looked at. So there's so much ground ground you know ground swell of activity um and I think these small investigator LED studies, typically they are small because trials are expensive.

Um i'm gonna be reporting positive results. So I know what we're sing and I will be, you know, for see now least four trials, always really positive results in very difficult to treat disorders. And that's just ask, I know that so much elsewhere, diction disorders as well.

And I much Johnson's work, obviously, Michael bogin shoots. So all this compelling grows. Well, it's really something. And yet, you know the system to really make a big breakthrough in terms of licensing ing is, of course, slow and it's so that can frustrate people. But IT IT has he has be done .

properly. Else we we revert back to what happened in the seventies where there was a lot of interest in psychiatric is come interesting to me. There was A A close drugs, opposition of meditation and kind of behavioral approaches to us, self directed state change and psychodeviant s meditation kind of made IT through the hatch. I think there were some years where I was considered kind of counterculture, woo, magic carpet, weird stuff by western science um but now I mean there are tens of thousand.

Tens of thousands is not another statement of quality studies expLoring how meditation can provide advantages for the mind and even for mental health um and psychotic xs are now catching up but they used to be close cousins in the in the cultural framework but the problem was I think pyi could alex were reviewed as making people crazy and university professors lost their jobs for having discussions like the one that uni are having right now um and some people went to jail but mostly people either left academic institutions or lost their jobs. Where as now these are some of the these studies of the sort that you are doing that are taking place at stanford and hopkins and elsewhere are some of the greatest magnetic poll for philanthropy for universities. Donors are very interested in supporting these sorts of studies because they and their family members and people they know suffer from psychiatric gillers.

For which um the current big farm approaches simply haven't worked. So it's sort of interesting to me that what once was seen as kind of poison is now being viewed as uh, a potential therapeutic. C uh, it's not just interesting. I think it's hopefully IT speaks to the evolution of of the human species. People seem to be becoming more open minded about becoming more open minded.

yeah. Yeah it's a that so much as happening so fast and is, you know there are elements of its complexities ying the space that there is critique. There has been some bad practice in psychiatric therapy, boundary crossing issues that have cause some scandals .

that's too bad. Isn't IT yeah. Well, you know, I think to the gene therapy, right? IT just takes one bad incident.

Your 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's slowly started ratcheting up again.

Gene therapy broadly to find an hour in the age of, you know, potential directed gene theri using Christopher and things that which makes people, some people cried and other people very excited. You know, you have huntings in your family. Crisp a is like the most exciting technology ever because you could potentially eliminate IT from your family one going forward, of course.

So I just really hope that we can be baLanced as this all plays out because IT could go similar way, given the stigma, given the history that people be very twitchy with with some mis olathe incidents um and and I over journalizing them perhaps um in a sense 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 be done right and and what the necessary safeguards and and standards should be um uh yeah IT won't be IT won't be an easy right forwards but but let's help you we got a hope that they succeed because current treatment see are people talk about the mental of crisis and T O point earlier about ana rax I A rates.

It's not always actually the case when you look at the fp d meos gy, 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. I hadn't really progressed.

They have got any Better since the nineteen fifties, more or less, and and new drugs have been more of the same. So there haven't been any paradigm shifts. And that's why I get a little impassive when I talk about psychiatric therapy at 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? Uh, sure.

And not everyone will want to trip and that will terrify some people so much that they'll just want to be on the lexi pro or or an psychiatry, psychology, whatever. And of course, you should be allowed to have those options, of course, and the more options are Better. Um but I think there is is great value and really understanding what psychiatric therapy is. And and I think when you do, you realize that this is a major chAllenge of many levels and 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 psychedeli C2Be add ed to the arr ay of pot ential tre atments. 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 curate 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 um is so important um so I want to extend A 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 a 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 outcome. So I just want to say thank you for that.

Also thank you so much for joining us today to share this immense knowledge. Said 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 and also in your caution about explaining how some of the results, in particular in antiqua fibre biogas are perhaps preliminary but very exciting.

They're not published yet anyway, we went call them preliminary, and also for touching on mechanism that is not just about people feel Better， but pointed to some potential underlying mechanisms in terms of connectivity changes and on and on. So 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 be appropriate for them. But just thank you, thank you. Thank you. Such important work you're doing, Robin.

thank you. Andrew, been a pleasure.

Thank you for joining me today for my discussion with doctor Robin car heart Harris. I hope you found IT to be as informative of about the science and clinical uses of psychodeviant s as I did. If you'd like to learn more about doctor car heart Harris research, or support that research, or inquiring to being a research subject in one of his laboratory studies, please see the links in the showed captions.

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