#377: Psychedelics — Microdosing, Mind-Enhancing Methods, and More

Optimal minimal. At this altitude, I can run flat out for a half mile before my hands start shaking. And I asked you personal questions. No it is. My cybernetic organism, living tissue over metal and those cells. No

Hello boys and girls, this is Tim Ferris, and welcome to a very bucolic episode. I'm sitting outside with the birds and the bees, the flowers and the trees, of the Tim Ferris show. where it is my job to interview world class performers or world class experts, people who are in the top of their fields. And this episode is a panel. The panel relates to psychedelic science and it was recorded at the 2019 Milken Institute Global Conference.

And this particular panel was standing room only. There were several hundred seats, all filled And then the entire room was surrounded by people standing. Which was really surpris and also encouraging. to me because this is a conference comprised of primarily

investors, many of the best investors and uh certainly Most Lauded. and uh objectively in many respects successful CEOs in the world. Very, very unusual uh to to see that type of crowd in that room.

And a few notes before we jump into it. It was a fantastic experience. Uh a lot more to share another time on that. Uh We have a number of different types of participants in the panel. We have incredible scientists. We have investors

And we also have writers who have experimented microdosing. And there are a few visuals. that are referenced in the beginning, a number of slides that are presented. You don't really need the slides to understand what is being said. Uh And I'm a nerd for the science.

Uh. you will be able to find those slides and links to the studies at Tim.blog forward slash podcast with all of the other links to everything mentioned in this episode. So if you go to Tim.blog uh you will certainly be able to find this episode and find all of the visual references, but you do not need them to

in the first, say, nine and a half minutes. If you want to skip directly to a first person description of microdosing and what that is like or what it can be like, I should say. And certainly not recommending that you do anything that breaks the law wherever you happen to be. Colour within the lines would be my recommendation.

But if you are Curious nonetheless, for informational purposes, what such an experience is like that comes up around nine minutes and thirty seconds in And without further ado. Because I do make

Because I do make For fuck's sake. I do make much ado about uh my introductions. Please enjoy this very wide ranging and detailed conversation about Psychedelics and psychedelic science.

Thanks for coming, everyone. I'll keep my introductory remarks pretty short. But I'd like to begin with a show of hands. How many people here know someone who is depressed despite the fact that they take antidepressants. Anyone? All right.

How many people have anyone in their lives affected by addiction, alcohol, opiate, or otherwise? All right, so the entire audience for both questions. Uh lest we start on a complete downer. Let me Give an inspirational story. And it relates to Catherine McCormick.

A name not many people know. I'd recommend that everyone look her up on Wikipedia. She was born in eighteen seventy five in Michigan. She was educated at MIT as an undergrad, where she lobbied the administration to change a requirement that women wear hats with feathers. Because they were a fire hazard in labs, she said. Very true. So they changed that. Uh she also

inherited a good portion of the international harvester fortune. And in nineteen fifty-three, she met a man named Gregory Pincus. who was developing an oral contraceptive. He had lost his funding because his backers didn't see any profit in sight. And over the subsequent years pretty much single handedly financed that development and in nineteen fifty seven the FDA approved the pill.

For menstrual disorders. So that was sort of the strategic first indication and then later we know what happened. And the reason I bring this up is that in total she provided two million dollars of funding. In today's dollars, it's around 23 million over many years.

And uh It was an uncrowded bet. through which she was able to completely bend the arc of history. And Uh I will give some disclosures now. So in 2015 I stopped all my early stage tech investing and redirected almost my entire focus to Psychedelic science.

for reasons that I think will become clear in this conversation. and have been very involved with both Hopkins and Imperial. So with that, let me introduce We have

Christian Anguda Meyer, founder of Epiron Investment Group. We have Robin Carhart Harris, Head of Psychedelic Research, Center of Psychedelic Research, Department of Brain Sciences, Imperial College London. Matthew Johnson, Associate Professor, Department of Psychiatry and Behavioral Sciences, Johns. uh Johns Hopkins University School of Medicine, and Iell it Waldman, author of A Really Good Day, subtitled How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life. So let's begin, Matt.

with uh some of your slides. If we can bring those up. And I'll let you take it from here. Sure. Side three. So Really important before we get into the meat of some of our other conversation is to let you know

That we've been ahead. uh as a field in terms of understanding, being very clear about the risks. There are downsides, so You ask any Jedi knight about the force, they're gonna tell ya, in addition to knowing the good side, you need to be aware of the dark side. and how to keep it at bay. Same thing with psychedelics.

The so called bad trip is real. There are other risks. As well. But we published a paper over a decade ago that has now essentially become the Bible Uh how to uh conduct these studies. It's been used by institutional review boards at a growing number of universities. And I was at the FDA last week. They are using these guidelines to evaluate

novel protocols. recently published another paper um Assessing the abuse liability and risks of suicide and and thoroughly reviewing the scientific literature and suggesting that if psilocybin

which is the active agent in so called magic mushrooms. if it's approved ultimately through phase three trials as a medicine, That It belongs in schedule four, based on the data, rather than schedule one. So We're aware of the risks, we're paving the way, we've analyzed the data.

Um in terms of some of the now we've got the the dark side out of the way. What's the light side? We can look at some of the efficacy data. Very quickly, so next slide number four, please. We published the largest a couple of years ago the largest study examining psilocybin in the treatment

of depression and anxiety Associated with a serious life threatening cancer diagnosis. These are people that are freaked out. Because they're gonna die. Um

And this is essentially like the addiction work in is picking up on older threads of research, largely done with LSD back in the sixties. You can I'll tell you briefly about our our results here on the right. Looking at our At depression results. On the left.

And then anxiety, um results in the right panel. the leftmost uh points on those figures under baseline That's those are the high levels that people had when they came into the into the trial. And trust me, this is a s a clinically severe level of

Depression and anxiety. Post one, the next time point on both panels. The Red Group has received a high dose of psilocybin. This is not a microdose, this is a very large, overwhelming dose. Something you don't want to be at a concert on. You see a huge reduction.

into the non clinical realm. I mean these people are not having problems at those lower levels. uh around uh eight on the scale. You do see a good reduction in the people in the blue group, and that's a group that to this point has essentially received a placebo. It actually is

a very small dose that you could call microdose. In this trial really just designed to serve as the comparison condition, essentially a placebo. So that's probably due to the very careful preparation, the rapport building, and also some of the so called placebo effect. At the next time point, post two, that's a month after they've re everyone has received the high dose. So the people who had gotten the trivial dose of In the first round

They have now also received a high dose. Now they have dramatically decreased their depression and anxiety, just like the group that got it a couple months before. And then the really mind blowing thing on the last point in both panels is that six months UC Staiн Reduction in депресі.

and anxiety Six months after treatment. From a single hido session. And so

In terms of depression, there's understandably a lot of excitement around ketamine, which is recently approved for the treatment of depression in that it has immediate effec antidepressant effects that last one to three weeks. Which is wonderful. Get ready.

'Cause we might be at an even higher plateau when it comes to sustained effects with psilocybin. Um So I'll jump to the the the next slide. These along the addiction angle we decided to do something novel that wasn't done in the sixties.

One of the interesting things is it appears that this isn't just specific to one drug or another, like methadone for opioids or nicotine replacement for smoking. But the anti-addiction effects of psychedelics seem to be broad based. They get to the psychological meat of addiction. So why wouldn't it work for Tobacco smoking, people have tried to quit smoking. We ran a a small open label pilot. We had dramatically uh impressive results

Um at six months We found that eighty percent of participants were biologically confirmed. as smoke free. breath samples, urine samples, you know, we trust people, but we verify. Um

Those results held up to to sixty seven percent at a year. And sixty percent at an average of two and a half years after there's After their uh

Target quit date. In in this study they had three psilocybin sessions, most participants. Just to Tell you how impressive these results are. The best medications we have

Um such as Variniclin, which is Shantix, gets up into the range at six months at about thirty five percent. Nicotine replacement. Anywhere depending on the study, between percent. And twenty five percent.

It was an open label study, so we have to be cautious. The the real question is is Does it s warrant follow up? And the answer to that is APS frequent Lutley. And so we're in the middle of that randomized trial at this point. So this is just a taste of a a number of trials that have gone on the in the field. That are telling the same story that the earlier era of research from the 50s through the 70s showed, that there is huge potential of these psychedelics in treating a number of psychiatric Disorders. Thank you, Matt.

Uh Ayola, let's jump to you. Uh because I th I'd like to contrast, or maybe not contrast, but I'm not sure if I'm add to the scientific discussion the personal. discussion and and your experience. Could you talk to how you ended up microdosing, what microdosing is And what effect it had. That's a very big question, but I'll I'll let you

So microdosing is the practice of taking a subperceptual dose of a psychedelic drug. I mean you can microdose anything, but in this case we're talking about psychedelics. So when I say subperceptual, I mean you do not trip. You do not have a hallucinatory experience. You see no kaleidoscopic colours. The idea is to take a dr dose That you cannot perceive of any effects, but that there is something going on metabolically. So um I was experiencing serious depression. And uh I had not I had been on SSRIs, I had been on mood stabilizers, I had been on various medications and they weren't working effectively.

And so I decided to try microdosing. I had been a uh professor at UC Berkeley's Law School and taught a seminar called The Legal and Social Implications of the War on Drugs, during the course of which I read the psilocybin research, I read the research that, you know, from the very from the nineteen thirties on through the present day research. And um I was I you know made sure that what I was doing was safe, I made sure that the drugs that I was taking were pure. That is the most important issue. When drugs um are illegal, you have no guarantee that what you get when you buy from the illegal market is actually what you think you're getting. And I embarked on a 30-day experiment microdosing with LSD.

So what I did was I took a one-tenth of a dose. If you want to say have a hallucinatory experience at Burning Man, you're going to take somewhere between 100 and 200 micrograms. LSD is a very potent drug, so we're not talking milligrams, we're talking micrograms. I took Ten micrograms. And I took it every three days.

Profound. So the first day I had been in a suicidal, intractable, and hedonic depression. For what seemed like forever'cause when you're depressed you have very little capacity to remember when you weren't depressed. And the first day I took the drug I swallowed it early in the morning because LSD is activating and I didn't want it to interfere with my sleep.

And nothing happened. So I thought all right, well this was a bust and I got to work and about after about I looked out my window. And my dogwood tree was in bloom.

And I had this thought. Oh look. The dogwood is in bloom, it's so beautiful. Now it wasn't like the petals were bursting into color and taking off butterflies in the sky, but I had been unable to appreciate beauty for months.

And I saw it. And I understood it was beautiful and it made me feel happy. And that was an experience that was really mind boggling. Over the course of the next period that I was taking LSD microdoses, it wasn't like every day was a really good day, but many days were really good days. And um my set point of depression dramatically changed.

Um my productivity I wasn't in it for mind enhancement for productivity enhancement but my productivity changed dramatically. The book that you can buy afterwards at the bookstore Was the first draft of that was written in a month. Now I've done that before in periods of hypomania. But I had never done that in a period of Productive calm flow.

Um So uh I became convinced at the end of this experiment that this was a drug that had all the Theraputic benefits that are promised by SSRIs

But I often say that if those antidepressant commercials showed a fat person lying in bed not having sex, that would be a more accurate assessment of their effects. Then a happy lady skipping through a field of flowers. And I was a happy lady skipping through a field of flowers. Yeah.

That's great. But The microgram milligram difference is very important, so please take close note of that. Uh Robin, let's jump to you next, because

Uh I really want to get your perspective on Plausible mechanisms. plausible explanations for how these compounds do what they do. Because it's not as though

at least in the way they're currently administered in in most cases. They're sitting in your system, saturating your system. For say six months. after the cessation of smoking. Uh, could you talk to Mm-hmm.

Based on our current understanding, based on your current research. What is happening? And uh maybe you could also touch on the the entropic brain. Sure. Okay, so The first thing to say is that these compounds are working on the serotonin system.

an important brain chemical that modulates a range of different important uh psychological functions we know uh mood especially, but also uh cognition and states of consciousness. And it it's a particular aspect of the serotonin system that psychedelics work on, a particular receptor subtype. It's called the serotonin to A receptor. And we know from a a a broad range of different evidences that this receptor is involved in Um you could um

uh uh summarise it as adaptability. flexibility, plasticity, Um there are a lot of these receptors in the cortex, an aspect of Um of brain that humans have so much of

And um so stimulating these two A receptors uh appears to um at a higher level have an interesting effect on The um regularity and the quality of brain activity, so we can characterise conscious states. uh in a way analogous to um

to waves. Uh when we record brain activity it it it's very rhythmic Um and as our conscious states change, that rhythmicity changes as we fall asleep. uh or if we're knocked out with an anaesthetic or we suffer some kind of brain injury, you'll see that um brain activity, um starts to look like sort of slow rollers on a on an ocean.

And um Related to that, the the richness of conscious experience drops away. It's very predictable, very steady, there's not much going on. We know if we look at normal waking consciousness that the waves look very different. You know, they're much more rapid. There's is much more richness going on. What we've discovered with psychedelics is that that richness is enhanced further. That was quite an interesting and novel discovery to our

knowledge, there hasn't been a state of consciousness found that shows that increase in the richness uh complexity of brain activity above the level of normal waking consciousness. That's a very mechanistic take on things. Um Uh another way to to look at this that's a way of characterising the acute experience

Another thing to emphasise, tying this in with the therapeutic work, is that the quality of the experience that people have under psychedelics appears to predict very reliably the therapeutic uh outcomes. And so you know these really amazing findings that the drug is well washed out of the body

and yet people months on from these isolated experiences are reporting improvements in psychological well being drops in uh depression and such like so what's going on there. So just quite briefly to talk about the therapeutic mechanisms and perhaps slightly frame it in a in a slightly more um

sort of human and and psychological way. We can think of a range of different um expressions of mental suffering. as being um underpinned by biases and beliefs. Whether it's in depression with negative cognitive biases, we've

think we are worthless and life is pointless or it's eating disorders where we think we're ugly or overweight, uh or obsessive compulsive disorder with those stamped in habits. And so um

Th there is this kind of commonality, this trans diagnostic commonality that that um that seems to relate to a very range of uh broad range of different um psychological disorders and What psychedelics seem to do acutely during the experience itself is they seem to relax beliefs. And open a window.

For change, for revision. And if that opportunity is seized with the right kind of um psychological support, then you can work towards cultivating the r uh healthy revision. of these pathological beliefs and habits.

Thank you. It it's worth noting also for people who aren't familiar that if if we're talking about psilocybin. which in the case of studies is synthesised. It's been used in the form of Slossy mushrooms by, for instance, indigenous populations including the Mazatecs and Mexico for thousands of years, one could argue, very, very effectively. So the there there's a good question, we're not going to dive into it right now, but

Астувай омост і сивілізація Excepting if you in Antarctica. have used psychedelic compounds uh and uh certainly for rites of passage but also with an objective along the lines of these enduring effects that that you talk about. Uh Christian, let's let's talk about

investment in this space and and why you're involved. Uh I know that you, uh, based on our conversation, certainly have very sincere interest in making these compounds more widely available to people who are suffering. And uh your biotech company, a Thai Life Sciences is currently one of the largest investors globally aiming to bring some of these psychedelics, including Sil7, back into the legal realm.

What prompted that? And Um how are you thinking about approaching it? Um okay, let's start because you have many investors. Um I'm a super coward.

Um until five years ago I'm I'm not exaggerating. I have never drank alcohol in my whole life and I come from Bavaria in Germany where this is like cultural uh Actually appropriate. uh to do so, but I I didn't because I was super I was a weird kid, so I I was super worried that uh my brain cells could die.

Um and um so I didn't drink alcohol, I've never smoked a cigarette, I've never smoked a joint, I've not never done anything else. Till like around about six years ago Some very, very trusted friends uh tried to convince me of magic mushrooms and I was like, You're clearly insane. Yeah, I'm never ever gonna do that. Um but then I They told me a lot about it, actually what Matt and Robin said and I do invest a lot in biotech, actually biotech is how I

started my career, I founded a biotech company so I was very inclined to read all the data and the data is very Compelling. So ultimately a year later I gave in. It was uh to uh to say that as well. It was a jurisdiction where it's legal. Um and it was under

a a very guided and very uh well set up protected uh session with a great guide. And um it was The single most meaningful thing

I've ever done and experienced in my whole life. Full stop. There nothing comes close uh to it. And uh which is, by the way, in a lot of studies, um I think it's a John Hopkins uh study where I think it was two thirds of the people.

rank it among the five most meaningful uh events in their life, among birth of a child, death of a parent. And I think one third roundabout ranks it among the the single most meaningful thing. So because I'm an entrepreneur Um I came out of the trip

Um the first thing I did I called my parents. Um Um because um yeah, I realise how much I love them and I never say it. Um and uh the second thing is was like this should be experienced by more people. Um

And I do think that the only way to do it I mean we have a lot of We have a lot of anecdotal experience like myself and like Ayala, then we have a lot of let's call it basic research. But uh unfortunately never These drugs

These various drugs have been brought to the FTA or in Europe it's called EMA. Sort of life cycle or sort of cycle how to approve any normal other drug you want to use for for medical purposes.

So I was like okay This should be done. Is anybody doing that? And so I'm embarked on the trip. And In a figuratively word. Um and um uh and met great people like George uh who founded Compass.

um who had the similar thoughts that this should become a medical drug mainly for the treating uh for treating depression and then other mental uh health issues. Uh this is where we are. Compass uh is in phase two B. Um I'm also back the company which is bringing our catamin, hopefully uh on the market, which is a sort of sub form um of ketchup in also for the treatment of depression, and we're looking on other

um psychedelics or wider mental health structure. Because I think if you look at the numbers, and again investors are very numbers driven. the whole mental health area and not just talking about psychedelics, but as well, as completely more or less neglected. uh been neglected over the last Thirty years. Because it was sort of um

Com the mind is a complicated thing. And I pharma companies, biotech companies thought okay, let's focus on cancer, let's focus on the more Tangible. illnesses and also to be fair Um depression our view on depression and

mental health has changed over the last decades like Fifty years ago, what we now call a depression, people would have said Go on with your life, go to the gym, train a little bit. get well, yeah. When when people came back from the Second World War and were

showing symptoms what we now would call post traumatic stress disorder. People said hey Yeah. I think the the the view on mental health has changed over the last twenty years. but also

I think we live in a world where mental health is becoming a problem because our world where we live in is very bad for our minds, especially for young people if you look at Instagram, whatever. That whole sort of way we live and we have started living the last ten, twenty years, I think is very, very bad. for for the state of our mind. Yeah, and this is why the numbers rise. We have three hundred and twenty million people suffering uh from depression.

And these are just the official numbers and most probably the the how you say the gray number um uh is is much higher. It became if you count sort of the side effects like people not showing up at work, And stuff like that. It became the single most kostly illness. um in the Western world.

And for like twenty, thirty years there has been no innovation and all the drugs which are on the market are not curing but numbing it. Yeah. And again let's go back to something personal. Like if if if a if a person gets very depressive because somebody loved one dies, you don't want to take Prozac and Prozac tells you you don't care about the death. you wanna sort of dissolve it and solve it in a in a different way, and I think this is

where psychedelics have a very a promising path to be a very valuable Truck. Thank you. And uh we're not going to probably talk about a very

Specifically today, but the efficacy of MDMA for post-traumatic stress disorder is is worth looking into. uh and is is really remarkable. Both MDMA and Solocybin now have uh breakthrough therapy designation by the FDA. uh which is remarkable. And if you look at the graphs, you look at the data.

uh for changes in PTSD severity from severe or extreme symptoms to asymptomatic. They look very similar to the smoking cessation graphs. It's it's incredible. MAPS is an organization doing great work there. I see um it's somewhat ironic that I'm the resident drug user because like you, Christian, I don't do drugs other than these. I don't I don't smoke. I don't like to smoke. Sometimes I take CBD because you know you can't get a matcha without it nowadays. Um Uh I don't like to experience any hallu I I I like my mind to be sharp at all times. But um

Uh because I was teaching the one of the s first sort of people who popularized MDMA, Sasha Shulgan, a chemist in Berkeley, used to lecture to my class, and Sasha and his wife Anne, who is a therapist, convinced me to um try MDMA, which is ecstasy. With my husband as a Tool of marital therapy. And we've done it.

Every couple of years since we have the strongest marriage of anyone I know. We're sort of famous among our friends for having an incredibly strong solid marriage. And I do actu we have four kids, we have a lot of stress. But The what MDMA does and why it's relevant I think to PTSD is it's somehow and these guys can probably talk more accurately to it, it disconnects the the emotional experience from the memory, which allows you to um deal with the trauma of memory without the intense overwhelming emotion negative emotional content. So in the context of something that isn't PTSD, but is rather like the You know.

mundane PTSD of a long marriage. It allows you To Talk about your issues. But Фрама плейс в конечно.

So every couple of years we spend six hours talking about everything that has come up for us. From a place of absolute love and commitment. And that sustains that one experience will sustain. For as long as two years. It's really remarkable. Thank you. Not to delve too much into any current use, wouldn't want to.

Implicate anyone. MDMA is w worth taking a very close look at. Uh there are risks associated associated with some of these comments. Yeah. So there are some risks associated with these compounds. These are not panaceas. They are very effective or appear to be for certain conditions. MDMA has certain uh say cardiac risk. In some patients, for instance, since it is

uh what is it, methyl dioxymethamphetamine. Um there is that. Uh I might be getting the chemical name wrong, but uh then you have risks with, say, certain other promising psychedelics, IBogaine, for potentially opiate addiction, which I want to ask you about, not specific to Ibogaine. You have in the case of ketamine some addictive potential, which I've certainly seen in even experienced psychonauts, so you have to be Careful with how it's administered. But the uh I won't.

talk too much about this, but the toxicity profile of many of the classic psychedelics. Like psilocybin is is remarkably Um appealing. Uh Matt.

Just speaking to the the toxicity Or potential toxicity of say psilocybin and also uh based on what you've seen with tobacco and other forms of addiction.

Uh if you think there might be applications to say opiate or opiate addiction. Sure. So for toxicity We can start

А те фізіологіка лево This is true for psilocybin, LSD. Dimethyltryptamine or DMT, which is in ayahuasca. There is no No.

Lethal. Overdose. No dose at which there's any observable organ damage, n not even a potential mechanism. For neurotoxicity.

Um That's pretty freakish. Cannabis is similar. You'd be hard pressed to find anything sold over the counter. Um at C V S Walgreens that you could say this about. You can't say it about caffeine, aspirin.

Most drugs you can't just Take ten times an effective dose and expect to live. Or to be un undamaged. So remarkably freakishly robustly uh safe at the physiological level. I would never say any drug is safe, period.

It dem it it it depends on what area of risk you're talking about. Um So these are Very in sufficient doses

Um profound Altering drugs. very intoxicating, if you will. When you see harms, they fall into a couple of categories.

One that's applicable to anybody that takes a high enough dose. is what people out there call the bad trip. In clinical research we refer to these as clinical experiences uh as as challenging, I'm sorry, challenging experiences, because in fact they can be very um helpful themselves going through extremely difficult experiences. nonetheless we try to minimize them. But out there in the wild, so to speak, recreational use or what have you. Um and it's certainly a small minority, but sometimes

um a an overwhelming anxious state can lead to dangerous behavior. Someone panics, they run into traffic, You know, it was overplayed in the propaganda of the late sixties, but falling from heights. Um It has happened, they're very intoxicating drugs. Far more people have fallen from heights when they're drunk. But nonetheless.

It has it happens. So um in terms of public health this ranks lowest amongst all the other major legal and illegal drugs, but nonetheless there is a risk there. So

Nice thing is you can squarely address that in clinical research and potential clinical use. um through preparation and monitoring. It's never it's not take two and call me in the morning. follow up care. Um the other major area of risk with these classic psychedelics.

is only applicable to a a small percent, one or two percent of the population who have active psychotic disorders such as schizophrenia. Or a strong signal. for that predisposition. And many of the kind of urban legends we may be aware of are folks that

T It seems Very convincing that those folks had a predisposition at least such as you might be familiar with Sid Barrett, the original singer And the Pink Floyd.

Um Mm. And in the earlier era of clinical research with LSD with thousands and thousands of participants, the the only people that had prolonged psychiatric reactions beyond the time course of the drug. uh were those individuals with that psychotic predisposition

It's also very fortunate. like the bad trip side that we can squarely address this. in clinical research. and eventual clinical use Um there are extremely reliable psychiatric structured screenings that can identify

Peep that small percentage of the population that has this risk. And then it does modestly raise blood pressure. Um so we can't uh run people through the research who are at an extremely high level. I mean these are the same folks that might have a cardiac event if they go up several flights of stairs. Nonetheless, that's a real thing. Um

And uh Also in the area of risk, we we documented some systematic effects in increasing the chances of a headache. Within the day following Use Typically not in a severe category, nothing that we would think

Would prevent people from um using it. Uh clinically. There's a very rare thing called the hallucinogen, um uh

persisting perceptual disorder, extremely rare. Tends to be well it's All the data show that it is exc exclusively associated with recreational use, where there's typically multiple drugs including alcohol used and there may be a predisposition there. It's never been observed. in any of the thousands of potatoes.

participants in the older studies or the current studies. Um uh So You've heard of the term flashback, and that can mean many things, but that what this refers to is having persisting

perceptual abnormalities That severely hamper the qu uh uh quality of life. They're very distressing for individuals and it

It seems to be that that's it's probably related to a neurological susceptibility. where other events not only psychedelic drugs but other medications, other events could probably cause the same sphere of of r known risks. Thank you. And what about uh applications to

say opiate opioid, right? And just if I could I'll add just a quick personal note. So my cousin by marriage Uh he had a hereditary disposition to schizophrenia. and really abused LSD all throughout high school and college. And it would seem that it expedited the onset of symptoms of schizophrenia.

although very likely that he was headed there already, it just hastened. The path. So I've seen that firsthand. Um And uh

На флипса ввоза скредил ауз. uh on a personal level that is representative of of I suppose uh sort of pandemic level problem in opiate abuse. So my best friend uh Long Island died of fentanyl overdose, my aunt died of percocet plus alcohol not too long ago. So this is something that's touched a lot of lives in this room. Are there any Potential uh applications you think or is or research worth doing that would Look at

psychedelics and something like O Peter, Opiader Absolutely, it's a very promising area. There was one study published in the early seventies using LSD with heroin addicted individuals. Um

There was, you know, we needed to do follow up, but that was right at the point in society where the rug was pulled out from this research and the research wasn't allowed anymore. But nonetheless there was a a a good initial signal. of long term success. And that's part of this. formula that I was describing earlier, this picture of

broad applicability to treat addiction. of various types. My colleague Peter Hendricks at University of Alabama Birmingham is is showing initial positive results in treating cocaine addiction. Um so opioids um is a is an extremely promising um area t something that we want to look at.

Um It's an extremely promising area, um, particularly in the midst of what's called the opioid crisis. And especially since opioid addiction is resistant to treatment. Um You know, we'd have medication assisted treatments now that

are more effective at keeping people off uh sort of resolving opioid crisis. problems, but without medication assisted treatment, opioids, you know, the the traditional treatments that we think of like narcotics anonymous, they are grossly ineffective. So our current opioid crisis will not resolve without wholesale accessibility of medication assisted treatments and I believe without really evaluating the potential of psychedelic drugs. Um Which is why I actually hope that this crisis might

Інхар рецептивні to d taking Um psychedelics down from schedule one, which means that they're the most criminal drugs. There is no A schedule drug mean drug schedule one drug means there's no medical use.

And it's the most illegal drug down to schedule four. So what kind of what other drugs do you think of that we could analgize that are on schedule four? Oh many of the benzodiazepines and the sleeping aids are in schedule four. We can talk about perhaps the broad applicability. And perhaps some

current diagnostic problems that we may have in psychiatry. Uh Because if you look in the DSM. And we can talk to all sorts of people who have previously been

Uh sort of at the head of mental health, Tom Insul and others. Uh where you have these disorders, these psychiatric disorders so called disorders that are very cleanly separate. Yeah.

anorexia nervosa. Anorexia has the highest mortality rate of any psychiatric disorder. Then you have O C D, then you have this, then you have that. They're all very much Side note. Ah, could you speak to the

Explain with the default mode network. Is if that's possible. Um Fascinating to me personally is that if we kinda zoom out to thirty thousand feet. As you mentioned earlier, you have this kind of hyp you have conditions associated with hyper rigidity, and then you have conditions associated over here, O C D, anorexia, et cetera.

compulsive behavioral or thought patterns, and then on the other side you have this hyperfluidity, which can be problematic like schizophrenia. But could you speak to Um Maybe explain for folks, if possible, the the current thinking around the default mode network. Uh sure, yeah. I mean it's gets some freedom rule so.

It does have that kind of chaotic component to it, but it also has the rigidity to it as well, if you think of uh fixed uh delusions. Um And so um This is a remarkable thing that gets kind of glossed over in psychiatry that uh

These diagnostic categories while they're there. Really to aid the clinician, um Uh That's one few. Another view is that they're aiding something else, perhaps drug discovery and uh

And such like and perhaps to some extent a myth that there are these crisp uh distinctions. that have crisp underlying biomarkers that following the the classical biomedical model we can come in with a magic bullet and and solve uh solve the situation and and if that was true then we wouldn't

B. Seeing the the mental health crisis that we're seeing at the moment, prescription rates of psychiatric medications are going up at record levels yet we're not chipping into the problems. So you know We do need some kind of major paradigm shifting

uh uh events here, a kind of black swan event that that that really changes things and uh Yeah. I think our collective view is that psychedelics psychedelic therapy is is that. model that's not just a drug treatment, it's more holistic than that. It's about managing context.

uh giving a drug that produces this suppleness of mind and then managing context to try and move people out of the kind of you know, entrenched ways of thinking and And um behaving uh into something um broader and more open. So the default mode network

Uh um is uh In a sense you could say it's the most um It's the strongest candidate that we have in the brain.

biological substrate of the self or the ego. Um it's a system that engages when we disengage, so to speak. Well we disengage from attentive focus. But we enter a kind of daydreamy, you know. uh internal imaginative state.

Um but uh this is very much tied in with with self and and the narratives that we Build about who we are. That we Start to believe in a kind of absolute

way that uh guides and drives our behavior. But can be so narrowing. You know, ego sees narrow and short. Uh and what you see under psychedelics is that this network breaks down. It literally

albeit temporarily disintegrates. and people see broad Um and uh they see the bigger picture analogous to the so called overview effect that astronauts have described when they uh are up in space. They look

look back at the whole of the earth and then they can put things in perspective and think, you know, Why was I squabbling with my uh wife or my work colleague um And and you know it's about seeing that that bigger picture. So Here, you know, we've got this opportunity through brain imaging to start to put a bit of meat on the bone, you know, to

Uh help um you know, lift the lid on this black box that's the brain. uh start to show people that this isn't magic. It might feel like magic, psychedelic therapy. But it rests very firmly on nature, on biology. um and I think it's useful to to add that to the conversation and and help

kind of ground the conversation about uh about psychedelic therapy. And Robin just uh touched uh uh something important where I disagree with Ayala and agree with Robin. that most psychedelics it's not true for all of them, but are a very holistic treatment. So partly the setting and the guide and

However, the experience is equally important. So why this is my opinion, especially, for example, on on magic mushrooms that yes they should be available as a medical treatment. but not over the counter. This is nothing somebody should do alone, especially when you're depressed. And by the way, we all I think one risk is that

Most people very passionately like All of us talking of psychedelics, we're not depressed. And it's a different experience. when while when you read observations of of treatment of depressed people, They might go through a

L'allow catharsis or to uh to a a challenging They might have a challenging trip, nevertheless the trip is healing them and the guide is very important. So this is why I just want to add that Yeah, uh I personally think yes, it should be available as a medical truck. This is what we're working on. But uh it should be available on the professional

care like with psychiatrists or in clinics, uh But not over the counter. Definitely not over the counter. I no, I agree with you entirely. In my book I have a whole sort of chapter about paradigms for decriminalization. And You know, my ideal paradigm for s for psychedelic decriminalization would be for lack of a better word the psychedelic spa. where you would check in and get that buttressing because in all drug experiences, but particularly in psychedelics, the set and setting are, as you say, are critical. Set is what you bring to the s experience and setting is the setting in which you experience it. So like, you know, the Canyon Ranch of psychedelics.

with f with you know licensed trained support team. I'm not sure you have to be a therapist per se, but someone with experience and training in supporting an individual. Ideally with preparation Both before and after. Which is not to say that I think all people um require that, but that is that is much more likely to engender a positive response. An interesting number is the Netherlands. It is legal. You can access psilocybin, magic mushrooms in the Netherlands, legally in coffee shops.

And The Netherlands have the same mental health crisis, then every So just the fact that

psychedelics are available, yeah, unfortunately do not change um the mental health crisis. It is really like the professional and I I if I experience it with people like I would look at my parents or or or friends who have depression, they're not making that leap. They rather go to their doctor because they trust them and then the doctor should be the one who's also uh administering that. So I'd like to touch on something you said uh actually but that we've sort of covered

Uh But offer a a framing that I think is is helpful and that is that Rather than think of good or bad trip, think of safe or unsafe trip. Because the

In in many cases the the difficult experiences are when you see the truths you prefer not to see. And you look at the behaviors that may be in your blind spot, and that can be very uncomfortable. Uh as in the case when a smoker's like wow that's disgusting, I saw that I'm killing myself. And they have to look at that hard truth.

Difficult. But safe. And that depends a lot on the context. And the providers and and so on. Uh question for you, Christian.

How do you think about creating business models around compounds that can be so effective with a single dose or two doses because I I I know you want this to be available to a great number of people. that requires a sustainable model of some type. And there are many different ways to approach it. You know, MAPS has one, with say a B Corp that does drug development, then there are for-profit options. Uh how do you look out for temptations like taking something that is so effective with one or two doses and create

creating something that requires a maintenance dose multiple times a week. Is it the therapeutic wrapper, that kind of spa element and context around which you build a business? How how do you think about that? Well first Um And meaning that sh sounds maybe cheesy when we say English, but like uh if you're investing in biotech, you really want to make a difference because I do other tech investments and I'm always very happy about biotech because if you succeed

in uh bringing a drug to market you really make a a difference in the world. So so I think it's not I think this is a little bit the must that everybody thinks biotech investors are like evilly plotting um how to make the most out of it. At least this is not how I think about it. We wanna cure people, um and and hopefully we're gonna make that happen. Um

Second, the market is so huge. Meaning I I said we have three hundred twenty million people and most and the number is rising and I think there are more people who are not diagnosed. So even if I would be very, very happy if it's a single dose pilocybin, which is uh which is helping those people, even if that's the case, the market is is huge. Then you have the uh the side business models or the as as I said, the spas and uh the the clinics you can build up, yeah, because it is all about the holistic. Um Thing and

And then even and we don't know yet. Meaning for a lot of things we also have to say, like we have very good indications, but we don't know yet. what is the right dose. This is, for example, what Compass is trying to figure out at the moment. It might be and I'm not saying that because It should be like commercially, but it might be that you say oh if somebody was depressed you should do it every year again. We don't know yet. We try to figure that out. But there is enough business uh and I think in general like Even if you go aside and look at meditation app like Calm, for example. Like

I think the the whole mental well being like Treating people who are ill have mental health health issues but also keeping people healthy Yeah, in our current environment and and this will get worse. My personal theory is that That our brain

Uh has like actually resilient, so like a immune system which is based on faith Um love and purpose.

And if you look at what our world is happening, we take these three things away. Communities are dissolving, Families are dissolving, so you have G C said a little bit less love in the world. Yeah, then most people know that the world will look so different in twenty years. that uh that they don't have a purpose anymore. The bus driver knows that in twenty years most likely his bus will be driven

by an artificial intelligence. Yeah and uh and then we have a a dramatic loss of faith in every sense, like religion, and in in any spiritual dimension. And it all will make people more impressive. So So Nikki said the market is growing, so I'm not worried about uh about uh how often you have to take it. Okay.

Thanks. Market is growing for better or for worse. Uh Matt, I'd like to I'd like to come to you first I'll just I'll I'll make another personal note. Uh And um

Try not to directly implicate myself here, but So I my family has uh a on both sides quite a bit of severe depression. And I would say every six months or so.

As an adult, I've had a major depressive episode. Almost killed myself when I was an undergrad at Princeton. I've written about that if you guys want to check it out. Uh in the last five years I haven't had a single And here we are on this panel. I'll let you guys draw your conclusions. Not to say that that is going to be true 100 percent of the time, but given the fact that in one could argue that there have been incredible advances scientifically in cardiology and neurology in all these various fields.

And then you look at psychiatry, and there's been very little, I mean, aside from SSRIs some time ago, and now ketamine, which is very interesting, I think, for uh acute suicidal ideation and chronic pain, especially. Uh but there's there's very little that has happened and um So I'm I'm very, very invested in this space. Matt, the reason I wanted to come to you next is that you mentioned Schedule I and Schedule IV. Uh one question that people might have on their minds is well wait a second, if these are so great

If they have such low toxicity, how did they end up in a category, schedule one? which is no known medical application high potential for abuse, among other things. Which of course based on the data I disagree with, but like how did that happen and how do we get out of that. Yeah, my not so secret agenda is to

set the conditions over the next three to five years with private philanthropy and so on. so that I can then work separately to try along with other people to help get federal funding for this stuff, which is not currently forthcoming. Um so how did we get To this. Very

difficult and expensive position. of operating from schedule one and how do we potentially get out. Yeah, this The quick answer is that psychail it was really because of the association with the counterculture and everything associated with it.

In the late sixties. early seventies. And I would say that that the culture was essentially Traumatized.

From um that kinda early Introduction uh of psychedelics and And and there were casualties when they were used. Broadly. There are also plenty of people said it changed their lives for the better and

They're still here to to talk about that. Um but this this came about right at the time when the federal Framework. for controlling uh schedule drugs, the controlled substances act. It's being developed.

And Um There is no there's some flaws in that system. There is no category, for example, of having um no accepted medical use, but mild to moderate abuse potential.

Um you know you jump from uh having no accepted medical use and high potential for abuse in schedule one to schedule two something like cocaine or methamphetamine, which are schedule two. Um As as having uh high high potential for abuse.

But um accepted. medical uh value and those two drugs are used. Uh medically and are approved. Um so there's really no framework. Now, you know, still aside and the language is important here. It we squarely know at every level of science

the the effects in the mesolimbic brain structures. involving dopamine, the epidemiology, reliable animal models of reward. We know that these aren't drugs of addiction. Solidly. Um But they are

They can be drugs of abuse. And that simply means used in a way that can ca can harm you or the people around you. So, you know. couple teenager teenagers go out driving on mushrooms. That's abuse. Or you get into a pattern that interferes with your family relationships. Excera. Um

So they really don't belong in in in the again, the controlled substances act is is rather ambiguous in they refer to abuse potential which can include addiction potential, but also other risks. So they do have risks. You could argue they have you know these classic psychedelics. mild abuse potential. Um

But The other side of that is there's there's no accepted medical value. Um when the controlled substances act was originally um Uh Adopted.

Th it wasn't clear what that really meant and through judicial precedent it became solidified that that what that means is FDA approval. for an indication. So that's where we're at now. So until one of these draw until psilocybin is approved for an indication It's gonna by definition remain in schedule one. promising indications currently or those that are furthest along.

Based on the data, um, the most promising indication would be Depression and anxiety, you could call it psychiatric distress. Associated with a life threatening cancer diagnosis. That's what the most modern uh most cr uh

Advanced research with psilocybin. as a therapeutic uh has been focused on there's three randomized studies in that category. And then Secondary to that sort of as a class are

Um psilocybin in the treatment of of uh smoking cessation as a smoking cessation medication. I showed you some data. treatment of alcoholism. Uh a colleague Mike Bogenschutz at NYU has done some great work with that. And and then Robin's published work.

Um depression outside of cancer. So all of those those three things have been Uh those are published results with open label non randomized pilot studies. So They all look very promising, but they haven't um gone the published data hasn't reached that level of large randomized trials yet.

All of these disorders. are associated with being stuck in a narrow mental and behavioural repertoire. And as Robin suggested, I think that's why we're seeing efficacy with these nominally different disorders. Psychedelics have a way to blast one out of that narrowed mental repertoire. Thank you.

Uh I only Where would you hope? What would you hope this uh this field that is broadly speaking psychedelics to look like a few years from now. Do you have anywhere you'd like to see it?

Well, you know, um because I I went I was a lawyer and I I was a criminal law professor And so I think through this criminal justice lens. And I remember a period where Decriminalization of marijuana seemed incomprehensible. When we first started working um and I was working with the drug policy alliance on state initiatives to decriminalize marijuana, it seemed Um

remotely possible that in some very liberal states you might have a medical model, and absolutely impossible that you would ever have a recreational model. And I don't know about you guys, but I've been to these pot clubs which are like Apple stores and the bud tenders are, you know, showing you weed that in my lifetime as a teenager in New Jersey I never saw anything approaching. So there is a kind of there there the shift is possible. I think we could see A medicalized model specifically for psilocybin. The reason that this research is happening in psilocybin and not LSD is because of the sort of fear associated with LSD, but they operate, wouldn't you say, Matt, almost identically in the brain. So I think we will see over the course of the next decade a sh and maybe even less a sh a shift to a medical approach, maybe maybe changing the schedule or maybe on a statewide basis. having this as we did with marijuana. Marijuana is still schedule one federally, it's still a crime federally, but we have different models state by state.

Um And uh I think that we are a long way from a decriminalization model for other for drugs generally. But I do think psychedelics, because of the research that these gentlemen are doing, does have great potential for medical applicability. And I actually think what can drive that more effectively than anything else are the individuals in this room and others like this Which is why I'm speaking to you, and I imagine that's why Tim is here as well, and maybe the rest of the panel, because what we need is a model of investment and corporate

pressure to change laws. I mean That's the way it works in America when there is A wave of uh of capitalist interest it's a lot easier for laws to change. We are up on time. Closing comments real quickly.

Check out the research. This these are not panaceas, but they are the most exciting thing that I've been focused on for the last several years. It's worth looking at. You have a chance, if you're interested in being on the playing field at having a Catherine McCormick level of impact. It's a big deal. Uh so please take a look, check out everybody on the panel.

And uh I uh Iell it and I will be doing Book signing over there. There are a couple of chapters in Tools of Titans on the psychedelic stuff as well. And uh thank you all for coming. And ladies lady and gentlemen, thank you for coming. Hey guys, this is Tim again. Just a few more things before you take off. Number one, this is Five Bullet Friday. Do you want to get a short email from me? And would you enjoy getting a short email from me every Friday that provides a little morsel of fun for the weekend? And Five Bullet Friday is a very short email where I share

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