Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew huberman, and I'm a professor of neurobiology, and opthamology at Stanford school of medicine. Today. I have the pleasure of introducing. Dr. Matthew Johnson. Dr. Johnson is a professor of Psychiatry at Johns Hopkins, school of medicine where he also directs the center for psychedelic and Consciousness research. As many of you know, there's extreme excitement.
Out the use of psychedelics for the treatment of various disorders of the Mind. Dr. Johnson's laboratory is among the premier Laboratories in the world. Understanding, how these compounds work, how things like psilocybin, and LSD and related. Compounds, allow neural circuitry in the brain to be shaped and change. Such that people can combat diseases like depression or trauma or other disorders of the mind that caused tremendous suffering. Dr. Johnson is also an expert in understanding how different types of drugs impact.
Act different types of human behaviors. Such as sexual behavior risk, taking and crime. Dr. Johnson and his work have also been featured prominently in the popular press such as articles in the New York Times and Michael pollan's book, how to change your mind and in a feature in 60 Minutes about psychedelics and the new emerging science of psychedelic therapies for treating mental disorders, during the course of today's conversation. Dr. Johnson, and I talked about psychedelics at the level of what's called micro dosing.
Not. It is useful for the treatment of any mental disorders. We also talked about more typical macro dosing, what those macro doses entail and he walks us through what an experiment of a patient, taking psychedelics for the treatment of depression looks like in his laboratory from start to finish. The conversation was an absolutely fascinating one for me to partake in. I learned so much about the past present and future of psychedelic treatments and compounds. And indeed. I hope to have dr. Johnson on this podcast again.
Again in the not too distant future, so that we can talk about other compounds, that powerfully impact the mind and human behavior. And perhaps can also be used to treat various diseases before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however, a 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 athletic greens.
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And of the meatballs, so again, that's Bell Kempo.com huberman, and enter the code huberman at checkout to get 20 percent off your order. And now, my conversation with dr. Matthew Johnson. Well, Matthew, I've been looking forward to this for a long time. I'm a huge fan of your scientific work and I'm here to learn from you likewise big fan and happy to do this with you very well. Thank you. My first question is a very basic one, which is what is a psychedelic.
Like we hear this term all the time, but what qualifies a substance to as a psychedelic
nomenclature is a real challenge in this area of psychedelic. So, starting with the word psychedelic, it just, if you're a pharmacologist, it's not very
satisfying because that term really
spans different pharmacological classes. In other words, if you really
concerned about receptor effects, in the basic effects of a compound, it spans several.
We'll come classes of compounds,
but overall, so it's really more of a cultural term or it does have a relationship to
drug effects, but it's at the at a very high
level. So all of the so-called psychedelics across these distinct classes, that I can talk more about the way I put as they all had, the ability to profoundly alter ones sense of
Ality, and that can mean many
things, part of that is profoundly altering, the sense of self
acutely. So when
someone's on the Psychedelic,
so the different classes that can be the specific pharmacological classes that can be called a psychedelic
are one that
what are called the classic psychedelics. So in the literature, you'll see that term and hallucinogen and psychedelic roll. Have traditionally been used synonymously. I
There was a little bit
tendency to stay away from psychedelics at the baggage. But there's been a return to that in the
last several years, but the classic psychedelics are classic hallucinogens are things like LSD psilocybin, which is in so-called magic mushrooms. It's in over
200 species that we know of so far of mushrooms
dimethyltryptamine or DMT, which is in dozens and dozens of plants mescaline, which is in the pay.
Coyote cacti and some other cacti like San Pedro. And even amongst these classic psychedelics. There are 2, structural structural classes. So that's the chemistry. There's the tryptamine based compounds like psilocybin and DMT and then there's the phenylethylamine based compounds. So, these are the basic to two basic building blocks that that you're starting from either, tryptamine structure, orphan ethylamine structure, but that's just the chemistry, the
Of the what's more important or at least to someone like me are the receptor effects and then ultimately that's going to have a relationship that the behavioral and subjective effects. So all of these classic psychedelics serve as Agonist or partial Agonist at the serotonin. 2A receptor subtype of Serotonin receptor, then you had these other classes of that you compounds that you could call psychedelic. Now, they're big one would be the nmda antagonist. So this would include
glued ketamine PCP and dextromethorphan something. I've done some research with which
folks might recognize from like Robo tripping guzzling like, you know cough syrup,
which is something kind of like high school kids are known to do and they can't get a hold of a real drugs that type of thing. So, a large overlap and the types of subjective effects that you get from
those compounds compared to the to a
Agonist classic psychedelics, but then you have
And by the way, this description this framework, I'm describing not everyone will agree. Some people will say no, psychedelic only means classic psychedelic. So there's different opinions here, but you have gosh Salvadoran a which is a Kappa opioid Agonist. Which
again is that come from
Salvia divinorum. It's a plant became 20 years ago with sort of popped onto the legal, High scene and there's a long history of this. You predating the internet going.
Back to like the stuff on go door in the back of High Times magazine and most of this stuff like never worked. You know, it's like the smoke enough of anything maybe a little bit lightheaded but this is one of those things that popped around 20 years ago, when it quickly got the reputation, like holy shit. This stuff actually works and works really strongly in these smoked extracts. Particularly people have these reality altering experiences on par with smoked DMT, the classic psychedelics. Oh, all
And and we did the first Blinded controlled human research with Salvadoran. A so lots of entity contact. So feeling that you in the experience of one is actually interacting with autonomous beings that type of thing. And then you have another big one probably should have mentioned even before the you know, Salvadoran a. But you have MDMA which really stands in a class by itself. So it's been called an intact Aegean and
and what does that mean?
It means like
touching within a sort of eludes the idea that it can really put someone in touch with their emotions. It's also been called in and pathogen. You can connect, can afford empathy, but I think in tacticians probably that's the term that I tend to focus on. And I know I'm not telling you anything, you don't know. But the for the, for the viewers that the primary mechanism of MDMA is serotonin release and to a degree other mono and
Bean release, dopamine serotonin and so structurally. That's also in the fen ethylamine class, which contains mesclun the classic psychedelic but also amphetamine so just like Adderall is in that thin ethylamine class. And so this is another example where chemistry doesn't dictate. I mean you can tweak a molecule in my head that same basic structure, but now you've profoundly changed the way it interacts with the receptor, so
So in MDMA does not, you know, exert its actions by like to say bye-bye, you know, mimicking, the baseball, entering the glove of the post synaptic receptor side, you know, acting as an Agonist so mimicking, the the the endogenous neurotransmitter serotonin, like the classic psychedelics do MDMA works, on the picture side of just basically throwing out more.
Natural the endogenous, something more sir. Don't be more serotonin. Flooding. Yeah,
synapse. So I get the impression that this psychedelic space is a enormous cloud of partially overlapping compounds, right. Meaning, some are impacting, the serotonin system more than the dopamine system. Others are impacting the dopamine system more than the serotonin system. Given that the definition of a psychedelic is that it profoundly Alters sense of self.
At least that's included as a partial definition. Can we break that down into a couple of subcategories? So for instance hallucinating, either auditory or visual synesthesia perceptual blending, the sentence that, you know, you can hear colors and see sounds, for instance, a common report of people that take psychedelics in, sufficiently high doses. So hallucinating synesthesia.
And then in terms of sense of self, you know, as a neuroscientist, I think, okay. What does it mean to alter a sense of reality? Really? What the brain does in a very coarse way is to try and figure out what's happening in space, physical space and that physical space could be within us or outside us. And what's happening in time, right? And as a vision scientist, the simplest explanation is when I move my hand from one location to another location. It's measuring the space.
The location of my hand in Space, over time and then you get a rate and a speed and all that kind of stuff, right? Yeah. That gets more complex as you get into the emotional realm. But is it fair to say that psychedelics are impacting the space-time analysis that the brain is performing and thereby creating hallucinations and thereby altering, you know, the blending of Senses. Is it fair to say
that?
I think it's fair to explore that area. And here's what I'm thinking, the clearly there is a change relationship, certainly at the right dose of orientation. In space time. I think as a I'm primarily a behaviorist and in terms of pharmacology, human behavioral pharmacology and always go to compared to pharmacology. Okay. What can we say that? Is it truly unique about the classic psychedelics or psychedelics in general? So with that disclaimer?
Option, I'm thinking, okay, alcohol can really screw up your, you know, time-space
orientation reception your balance, reassess particular. Yeah, you know,
and many ways. And so, in those gross motor ways like far worse, you know, of course, everything's dose-dependent, but in the classic psychedelics, you know, obviously the benzodiazepines being very similar alkyl. Same thing. So,
You know, I'd want to, you know, dig in a little more in terms of like maybe there's something more specific we could say about that relationship to time and space that the psychedelics are tinkering with. But I'm not sure it's an interesting hypothesis that the idea that that's a mediator that, that's something that there's something fundamental about changing that the representation in time. And in
space,
there might be something to that. And I think these is
Is psychedelics is profoundly altering models, you know, you know, we're all, you know, we're prediction machines and that's large so much of that is, is top-down and and and psychedelics have a good way of, you know, Loosely speaking dissolving. Those models, and one of it,
the reality of us, an example of one of the like a model, like, like I know that when I throw a ball in the air, it falls down, not up.
That's a that's a prediction that I learned as a child. I did not come into the world with a brain that knew that relationship between objects and gravity. But one of the first things that a child learns is the relationship between objects and gravity and their trajectories.
Yeah, and with a four-year-old. I mean I saw that at earlier ages like that, experimentation of like, oh, yeah, that's what happens, you know, right? So if
he were to throw a ball of your
Child were to throw a ball and it went up into the sky. That would be absolutely mind-blowing. It would
be for an adult to if you pre psychedelic experience,
probably right? And so there's there's a space. There's a rule there, you're saying, there's a kind of a prediction. There's a rule that that underlies, a prediction that when that rule is violated, all of a sudden, the circuit. Presumably for that prediction go like that. It doesn't have a mind Stone, but somehow it creates a surprise element or
Or a yakimaneeshin element,
and it's not filtered out, you know, and this might sound extreme, but there are these cases, it was over overblown, and sort of the propaganda, the late 60s, early 70s, but there are credible cases of people and it's very atypical of sounds like they really thought they could fly and you know, jump out of a window now. Far more people every year fall.
I mean, who knows? You know, they they fall and die out of you know from height because they're drunk, you know, so it's is extremely rare but you know, there are some like pretty convincing case that there was one research volunteer in our study that she looked like she was in one of our studies that she was trying to dive through a painting on the wall. She was fine, but she reviewing the video. It looked like she really
Thought that she was going to go through that painting. And so she was the other
dimension. Yes. To the violating these predictions. Yeah. I the reason I ask it. The question, the way I did is because given the enormous cloud of different substances and given the range of previous experiences that people show up to a psychedelic experience with I feel like the ability to extract some Universal themes is useful, especially for people who
Having done them before, right? You might not have an understanding of what their effects are. Like. Can we just briefly touch on the serotonin system and the dopamine system. I want to acknowledge it. As you already know that there are many neuromodulator systems in the body. Oh, and you know, the opioid systems cannabinoid systems, but there's something so profound about the serotonin system in the dopamine system because the way I Define a neuromodulator is, it's a modulator, it changes the way that
That other circuits behave in. Essentially it up. It increases. The probability that certain circuits will be active and decreases. The probability that other circuits will be ID in a in a general sense. So compounds like LSD lysergic acid. Diethylamide and psilocybin. My understanding is that they primarily Target the serotonin system.
How do they do that at a general level? And why would increasing the activity of a particular serotonin receptor or batch of Serotonin receptors lead to these profoundly different experiences that were calling model, challenges, challenging, pre-existing models. And yeah, I mean at the end of the day, it's a chemical and these receptors are scattered around the brain with billions of other receptors. Yeah. What?
We think is going on in a general sense.
Yeah. Yeah, and this is really the area of active exploration, and we don't have great answers. We know a good amount about the receptor level pharmacology. Some things about post receptor signaling Pathways. In other words. Just fitting into the receptor clearly, you know, serotonin itself is not psychedelic, you know, or else we'd be
trippin. All of us all the times when I eat a bagel I get certain and release, right? Uh-huh. I mean there's an artery. I mean there's tryptophan.
Right. My understanding of Serotonin is that engine? Very broad Strokes. That it generally leads to a state of being fairly pushes the mind and body towards a state of contentment within the immediate experience. Whereas the dopamine system really places us into an external view of what's out there in the world. And what's possible.
Yeah. Is that either do something? I mean that's consistent with my understanding and and and I'll certainly not in terms.
I don't primarily identify as a neuroscientist. Definitely tell the, you know, the viewers that were far more in your domain domain here than mine, but in terms of how psychedelics and Other Drugs, you know, interface at the
Neuroscience level, feel free to explain it at the experiential level.
Yeah. It doesn't have. I think
problem there probably are some audience members that are interested in, is that the 5H to see, is that the layer 5 neurons and courses that conversation, we could hold and that's an interesting conversation, but just in terms of the experience.
It's of serotonergic versus dopaminergic drugs.
Yeah, they, they do seem to create distinct classes of
experience. So I think that's, that's primary level for us to discuss
them. And in terms of how they end. I like. I'd like to explore the biology a little bit here and tell you, like, sort of what's known? And what's some of the ideas are please. Um, you have this path, you know, as you know, like, you know, these are levels of analysis and it's not which one is going on. It's almost like for the
Killer question, which level of analysis is most appropriate to is it you know is a question best addressed by the biology the chemistry or the physics. That's why I think of like receptor level post receptor signaling Downstream effects on other other neurotransmitters and then activation level effects and then coordination of Activation. So you've got the clearly the with the classic psychedelics the to a activation. We do know that there are Downstream.
Effects in terms of increasing glutamate transmission. So this is likely a commonality why, you know, ketamine is very psychedelic and slightly different way by the people who lose some, they don't Academy. Yes. Yes, and it's more dissociative. So someone is more likely to sort of be less behaviourally active, if they have a really high dose, they go into a k-hole and at the governor really high dose like you can desert. You're all the cable conscious. Yeah. I
got an a hole, but a cake,
a holy and it's very different. Um,
Decay hole in ketamine's interesting because people can take kind of bumps and kind of dance on it with the sort of an alcohol level strength of affect and that's sort of the classic kind of Raving, you know, use of it, but then those folks want to titrate their dose because if they do more of like a line, you get up to like
75 hundred milligrams, then you're talking about, you know, if you're on the
Dance Floor, you're on the floor and your friends are trying to make sure people aren't stepping on you. So that's like
why I hope so.
Buddy wants to take a dissociative anesthetic like to me. It's completely mysterious as to why someone would want to dissociate from their body.
People claim that these these the in these nmda antagonist. Psychedelics are extremely insightful, you know, in a very similar way to the experiences with the classic psychedelics. Oh,
and ketamine is now legal for therapeutic. Right rights.
Privado the intranasal form marketed by Jansen, which is s.
First one of the, yeah, it's prescription. And so
people are taking in the nasal spray. Yeah, and then are they undergoing talk therapy while they're doing this?
Typically not. So it's this very interesting and there's so much work that needs to be done. It's not treated as psychedelic therapy and by that psychedelic therapy, I mean, you tell the person they're going to have an altered experience, you tell them to pay attention to that experience. That they might learn something from that experience and afterwards, you
Us that experience with spur Votto. The model is its Privado is, is s ketamine. Okay. It's the the, yeah, the spray form of ketamine. That's it's been FDA approved for treatment-resistant depression, but it's you'll probably feel different ignore that. That's a side effect. That's an adverse effect. Just ignore it. We don't think that has anything to do with the way it works. But just get this thing. It's a direct, you know, sort of chemo therapeutic.
In a sense, it's not facilitating a learning process. Now, there's older work. There was a guy karpinski and Russia. That did extensive work with higher doses of quetta me. I should say spur Votto at the prescribed dose has isn't very site. It's a pretty low dose. It's in the mild psychedelic range, but it's not very strong. But this older work that happened in the 90s and early 2000s and Russia. They were using very high doses and treating it like a
Psychedelic treating it as if it was a psychedelic therapy, in other words, telling people you're gonna have this experience. It's going to, you know, we're hoping you learn something from it. We're going to help you through it. We're going to discuss it afterwards and they found incredibly High rates of success and some pretty well controlled trials for both heroin addiction and alcohol addiction. So I think a whole lot of work needs to be done now, and you see some of the ketamine clinics that are using ketamine off-label? A lot of them. Are you treating it like psychedelic therapy? There's
Essentially no research at this point on that. Do you get better results? Straight abusive spur Votto? There's some good variability, but it's antidepressant effects last about a week, but the kick in immediately. Now a week is a long time for like most most psychiatric drugs. Like you take it every day, right? You know, so that's amazing, but it's still just a week. We're seeing effects a year or more later with with, with psilocybin and and some of the classics like that.
That could be a pharmacological difference or it could be that they get a lot more mileage out of ketamine, if they treated it like psychedelic therapy. And so that's sometimes. What would that look like? Really? Just like our psilocybin sessions, which I know I haven't described. But briefly you have anywhere from four to eight hours of preparation getting to know the people who are going to be the guides or the therapist and the
room we have, maybe you could walk us through this. So let's say I were to come to one of your clinical trial
Because these are clinical trials, right? And in near your lab at Hopkins. Yeah, and what I need to be depressed or could I just be somebody who wanted to explore
psychedelics? We've had studies for all of these? Okay, and a number of other disorders. So healthy normal studies. Look at the code for not a problem to fix, but we're all here. That's what's amazing about psychedelics though, because you if you administer them under this model and you develop a relationship and give a high dose of psychedelic. You can be a healthy normal without a diagnosable issue, but man, we're all.
A human in the issues seem to come to a surface. So but we've done work with smoking cessation. So people trying to quit tobacco and haven't been
success over ID of reasons. So right, maybe I'll just ask some very simple questions that would kind of Step us through the process. So let's say I were to sign up for one of these trials and I qualified for one of these trials, I show up. You said I would do several hours in advance of getting to know the team that would that would be present during this psychedelic Journey
first their screening. So it's kind of like a couple of days of
Both psychiatric like screw structured in psychiatric interviews, about your whole your past and symptoms across the the DSM. The psychiatric Bible to see if you might have various disorders. That could disqualify you like the main ones being The Psychotic disorders schizophrenia and also including bipolar. So the manic side of bipolar. So after that sin also cardiovascular screening heart disease after that screening. Then the preparation where you get your both. You get you
Develop a therapeutic rapport with the people who are going to be in the room with you your guides, but you're also then didactically sort of explained about what the Psychedelic could be like and that's kind of a laundry list because they're more known by their variability. Then you know, it's going to have it's not like cocaine. Like you're going to feel stimulated, you're going to feel like, you know, you can do any, he's like, you know, or alcohol. You're going to probably going to feel more relaxed. It's like
I call them uppers downers and all around doors and the Psychedelic. So all around is it's like, yeah, you could be, you could have the most beautiful experience of your life, or the most terrifying experience of your life. So it's this kind of laundry list of like the things that could happen. So there's no
surprises. I think it's so important for people to hear because the all-around errs, they the, you really can't predict how somebody is going to react internally, right? Want to just briefly touch on something.
Because we left that topic but it occurred to me that a lot of these effects of psychedelics and how they function etcetera is still very mysterious. But then I recalled to mind that how most prescription antidepressants work is also very mysterious. They increase serotonin or dopamine norepinephrine Etc. But why they take weeks on end, you know several weeks to kick in etcetera is also mysterious. We're going back to the the the experience of coming to your laboratory. Okay, so
Let's say that, somebody passes all the prerequisites and the and it's the day. Yeah, I'm comes the day that they're going to have this experience. Are they eating mushrooms? Like you hear about or are they taking it in capsule form? And how what sorts of doses are you prescribing? Is there a dose response curve? Yeah, and then secondary to that like to talk about micro dose versus macro dose. So how do they get this stuff into? How do
People receive it and how do they get into
their box? So they receive pure psilocybin. So the mushroom and there are many species. The most private people have taken mushrooms in the United States, its most likely. So, so awesome. Be cubensis. They're easy to grow. They grow in cow patties. It's easy for any
body to grow them in their closet. It doesn't take a
thousand watt light like cannabis. It takes like a little, you know, 10 watt light bulb and a tupperware bin. So those are what those are the types of mushrooms of
People typically tape, we're not administering. Those psilocybin is the compound, you could draw a molecule psilocybin again, based on the tryptamine structure. Like, that's a single molecular entity. So
it's a white powder. Does it look like serotonin molecular lie?
Yes. Yes. Yes. So, if I looked as if I were to show
people the chemical structure of Serotonin, the chemical structure of psilocybin, it would look quite similar.
Right? Right, and they're
basically taking
serotonin.
A modified version of Serotonin, which makes sense. But then again, this repeated theme of the chemistry doesn't always neatly line up because like mescaline looks more like like dopamine than it does like serotonin, but yet it at the receptor activation level the pharmacologic neural pharmacological effect. It's those are similar, but but yeah, I mean and what it does at the receptor is an alternate. It's hitting the same switch, but then
Having an alternate response at the receptor
level. So for people that don't necessarily understand the relationship, between what we call ligand, the thing that parks in the receptor and The receptors, The Parking Spot, one of the reasons that you can get such a variety of effects from different compounds. Has for instance, serotonin, might affect a certain pathway at a particular rate and psilocybin might trigger activation of different components of that pathway different rate, since you get vastly different experiences.
Elsa's from two things that look chemically similar. This is also a good reason why people shouldn't just assume that they can Cowboy their own chemistry, right? That what you see on paper and what you can mix up in a while is often vastly different than what you predict.
Right? And there's a dose effect curve. That's really interesting. Some of our early work with psilocybin in healthy normals looked at a true Placebo Plus for active.
5 10, 20 and 30 milligrams of psilocybin, body weight adjusted. So, you know, those milligrams per 70 kilograms of body weight. We've recently published a paper in our newer trials where we're dropping the body weight adjustment because are going across hundreds of volunteers. We've kind of figure out that that you shouldn't really be. You don't need to be adjusting by body weight. So so
yeah. Well, brain size doesn't vary that much between individuals.
Yeah. Yeah, you
know, yeah.
And this is a brain effect. Mostly probably body as well. Okay. So the person ingests the yeah, powder Council.
Okay. Yeah, and it doesn't take 30 milligrams is a small. He could fit into a tiny little capsule. And it'll take about a half hour, what? Mean we're from 15 minutes to an hour to kick in
and Average. Joe's range was most of our
studies are looking at where we want a psychedelic effect are in the 20 to 30.
Like Graham range again because we have adjusted by body weight and the average American is over 70 kilograms about a hundred fifty pounds like people. And in fact have gotten more like 40 45 and a lot of cases, but it's still a small pill there. The session day itself is not full of, for most of our studies, is not full of tasks. We really want to look at the therapeutic response. Obviously, if it's a therapeutic study, we
in it to be a meaningful experience. And research has found not surprisingly that, you get a less meaningful experience when you're in an fmri, or when you doing a lot of cognitive tasks, we've done. Some research on, you know, a vat type for sure and plenty of colleagues have. But when you're in a therapeutic study, or if you're trying to understand the therapeutic effects, you have to recognize. There's this this this trade-off of what you can do. So our typical therapeutic model which again, is and just limited.
Necessarily to the therapeutic studies where we're trying to treat a specific
disorder.
It is is to have that preparation. So you're the person feels very comfortable with their guides me. Ultimately, what I tell people is like, any emotional response. It's all welcome. I mean, you could, you could be crying like a baby hysterically, like, that's what you should be doing, if that's what you feel like. And so in a lot of ways, sometimes people with psychedelic experience.
On their own, it can be harder to train them in this model because in the real world, people with psychedelic experience a lot of times, the rule is you hold your shit. So, you know, several friends, go to a party. They split a bag of mushrooms. It's like, you know, there's this social pressure for good reason. Not to be the guy, you know, in the corner of the room, where everyone is trying to just have a good time. Relax. I crying about your mother. Your other friends are there having an experience to and you're being a drama King and blah blah blah, and so
So like, yeah, compose yourself,
hold your doings. I mean, you're doing therapy for people. This is, it's not just about the experience.
Right? And the experience itself is very much shaped by by that that container the, by the environment and the degree to which one allows it to happen. Like one should let go of control.
Let's talk about the letting go of control. And then as we March through this hypothetical experience that does take place in your lab. So we're using a sort of generic.
Case example, if you will, the letting go of control is an interesting feature actually, because one of the common themes of good psychoanalysis is, or Psychotherapy of any kind, is that there's a trust built between the patient and the analysts and that relationship becomes a template for trust more generally and Trust in oneself. It's actually the the end goal of good psychoanalysis. Is that the patient actually one of the end goals is that they develop an empathy for themselves, which almost
Sounds like an oxymoron, but if you spend a little time with that statement, it actually pans out. So.
The Psychedelic experience is one in which chemically you're under a new new set of conditions, right? Yeah. Let's coarsely space and timer are altered in some way, sense of self. For instance. I might be going to a strongly interoceptive mode, where I'm focusing on everything within the confines of my skin. Whereas normally, we're sort of interacting in space and pens and conversation. And I'm sorry if I had occasionally, I'll pay attention my breathing, but I'm sort of dilating my and
You can tracking my focus for different things all the time.
The letting go of control, it seems to me could be sort of the expansion of one perceptual bubble to the point where you're not actually worried that that perceptual bubble is going to pop or that meaning you're not worried about what people think of you. Yeah, you're not worried whether or not your brain is going to explode, even though a thought could feel enormous. If I keep going like this. It almost sounds like Adele like but that's the idea here or if I'm paying attention for instance.
Was some somatic experience like the coursing of waves of heat through my body that I'm not suddenly saying, you know, is that weird. I'm actually just going deeper and deeper into it. So it's essentially expanding a perceptual phenomenon. How do you convince people to go further and further down that path? What do you think allows them to do that? Because I think that that to me is one of the more unusual aspects to psychedelics. Is that normally the the so
Social pressure, but also just our internal pressure from our own brain is pay attention too many things at once. Not just one is that
especially these days? Yeah, exactly task. Yeah,
multitask. And the more that we focus on one thing, the more bizarre that thing actually can appear to us. Right?
Right. I mean, even if it's the tip of your finger and you're not taking
any psychedelics, you spent a long enough, looking at the tip of your finger, you will notice when we are e weird Yang's,
right? That's I think that's the classic psychedelic effect or
One classic effect. And one of you is many times of this example of why people should necessarily, you know, these aren't
These one should be judicious in putting themselves in these circumstances. Someone could be, you know, having a very strong psilocybin experience and they're trying to navigate their way in Manhattan crossing the street. And they might be staring into the hand and really like, that's their hand is the most amazing Miracle, like the entire universe has essentially conspired to come to this one point to make this absolutely breathtaking. It's almost like I think of the simplest form of
Well, we know the simplest form of learning is habituation. Simply keep applying stimuli and there's less response. Like, this is, what organisms do is this is what we have to do. And it's like, there's this disc habituation component that like this obituaries. Yes, like that wouldn't be able to get through life if we wouldn't be able to cross that street. If we were like, oh, like, this is a miracle, like, so glad to know. I'm
so glad you brought this up. I mean here, I'm reflecting my bias has a vision scientist, but most people don't realize this, but if you look at something long enough, it eventually disappears to it.
It doesn't actually disappear, but perceptually it disappears. You have these little micro saccades that ensure that it doesn't but most of us don't look at anyone thing for very long, right? The the brains default is to perceptually jump around like crazy with the visual system with the auditory system. We all add that we will talk about add, a lot is sort of baked into our underlying networks at some level and then we have, we can force attention but it sounds like on psychedelics the one of the primary goals therapeutically is too.
Really drill into one of these perceptual Bubbles and expand that bubble. And the safety seems is the safety. It's sort of like a permission to to do that without worrying that something's going to happen.
Right? Because, you know, I've had people there on the couch. Yeah. I remember one lady said, this is probably 13. 14 years ago, said Matt tell me again. I can't die. Like I feel like my heart is going to rip through my chest. I mean, she was feeling. Alright.
And I should say, typically cardiovascular response is is modest the pulse and blood pressure go up somewhat, it can be dangerous for people if they're had severe heart risk and we do monitor this we do, you know each other I was ready to do a variety of devices. Yeah, so every half hour or so we take their on protocol and we you know, space it out a little further further into the time course, but we take their blood pressure and their pulse and if it goes over certain level, we have a protocol and we've had to do is only a few times, but physician comes
Give them a little nitroglycerine under the tongue and you know, knocks the blood pressure down a little bit, doesn't affect the experience. So we have it all in place, even though they'd probably be find out of an abundance of caution. Sure, but but yeah, but someone can feel that my God, I'm gonna die. Like I have never felt my heart beat like this before and like the experience of the breath can be just, you know, absolutely fantastic. And the sort of Nebraska is obviously interesting because
it's this audit automatic, you know, control. But it could also be voluntary. So people get into a sense of, like, what if I forgot it sounds silly. Like what about your baby, breathe? Exactly, but people can, that can be so compelling. And so one of the reasons I get back to one of your questions is like what do we do to kind of allow them to go further into these bubbles? It's a one is is wearing the eyeshades. We don't call them blindfolds because that has a negative connotation like being kidnapped.
And they're probably seeing a lot in there. Anyway, so blind isn't the appropriate.
Right? Right. That's, I've never thought I'd you should be like inter-site Shades, but
when you close the eyes, the levels of activity, in the retina actually are maintained, its Ponte is just
spontaneous activity and it seems. And I'd be curious about your thoughts on this. I mean, but the way I describe it is that the, you know, the mines, I mean, this kind of loose term, we use can be on rocket booster. So a
Lot of times for some people, like, a compound like psilocybin for some people. There's no.
Perceptual effect, like, if they're looking at this room, it would pre pretty much look the same sometimes folks. Like, yeah, things seem a little bit brighter. Now, some people will say, oh my God, there's waves that wall is waving and these curtains are, you know, I'm these compounds people don't typically see pink elephants. You do actually get that in another class. I didn't mention the anticholinergics sort of like atropine and Scopolamine those drugs. Those are, those are the true hallucinations where you thought you were having a conversation with someone who was never. There
it wasn't that.
We will definitely get to those. But when the reason I kind of cringe and say, oh my, when you talked about those is that knowing a little bit about the pharmacology of acetylcholine, the, the idea of manipulating that system to me sounds very uncomfortable because like the whole idea of what witches and flying, there was a whole history there, you know, hundreds of years ago, so-called witches taking these agents and then thinking they were flying around on broomsticks and
Things of that sort and and there's a lot of Mythology around the broomsticks. It's complicated. But but that sounds very unpleasant. One thing I about the the serotonergic. Let's just for with psilocybin.
So there's a person, an expansion of a particular fairly narrow. Percept. Could be sound good? Emotion, could be sadness could be a historical event or a fear of the future. And you've mentioned before that. There's something to be learned in that experience. Yeah. There's something about going into that experience in a, in an unknown, in an undeterred way that allows somebody to bring something back.
Into more standard reality. Yeah.
Given the huge variety of experiences that people have on psychedelics, given the huge variety of humans that are out there.
But what are now very clear therapeutic. Effects in the realm of depression. What do you think is the value of going into? This fairly restricted, perceptual bubble? What we are calling letting go, we're giving up control because if the experiences are many, but the value of what one exports from that experience is kind of similar cost individuals, that raises all sorts of interesting questions, and this is not a philosophy discussion. We're talking about biology.
In Psychology here. Yeah. So let's say I decide I'm going to focus on the tip of my pen. I mean, in the Psychedelic State I could fall in love with this pain. I do happen to like these pilot v5s and B7 is very much but I could feel real love. Yeah for the pain. Yeah, right. That's not an unreasonable thing to expect on our psyche in a psychedelic turn, right? And then the context of your laboratory model, which I think is a great one that experience would be just as valid as me going into the experience of some of the deep.
Action that I might have with a family member over my entire life span. Yeah. And yet the export from that, those two very fastly, different experiences is one of feeling a better relationship to the world and one cell, right? So what is this
telling us about pain and the processing, your childhood trauma both lead to, right? Yeah. So, what does this mean
at that level? It raises this question, like first of all, how why? I mean or just what are your thoughts on
that?
So this is definitely in the this is in the terrain we're figuring out, you know, so there's no the educated speculations. The best I can provide but I
I think the best the the most, I think the common denominator are persisting changes in self-representation. Okay.
Tell me more about self representation.
That's the way. One holds the sense of self the relate, the fundamental relationship of a person in the world. I mentioned earlier that these experienced seems altar at the models. We hold a reality, and I think that the self is the biggest model that I am a thing that
From other things and that's
I am defined by certain. I have a certain personality and I am a smoker. That's having a hard time quitting or I'm a depressed person that, you know, these myself as a failure and all of these things, those are models to. And I think, I think that change in self-representation maybe an endpoint for these different experiences. I mean, maybe the falling in love with the pain, the whole idea that your
Especially in contemplation, afterwards. And, obviously, I'm speculating here. But the whole idea that you could have such a deep connection with this random. Obviously, random aspect of the universe could potentially lead to this transformed, understanding of the self and like the pain may be a proxy for the miracle of reality. In a way that relies nothing on. I know Supernatural thinking, you know, you can be a hard atheist and take this
Ultimately, oh my God, like that, just like the pain. This is, you know, this is amazing. The fact that we exist until you get. There could be an extrapolation chair and use the pain, but I think it sounds so similar to Aldous huxley's. Classic description in the doors of perception of the chair and the drapes. Like, he took 500 milligrams of mesclun. He was just like, at a high dose of most. Yeah. Yeah, and that's, you know, that's a heroic dose for sure. And he just going off on the chair Enos of
The chair like this chair is exuded. The quality of being a chair.
Is this expansion of the perceptual bubble? A narrow narrow percept that then grows within the confines of that narrow percept. The so sense of self is a very interesting phenomenon and if we could dissect it a little bit, there's the somatic sense of self. So the ability to literally feel the self into this process, we call interoception and then there's the, the the
Of the self. The I am blank. Yeah, and I noticed you said that several times. It's intriguing to me. But a good friend. I don't think I can or should mention his name, but he had a very long and successful career. Within one of the more Elite teams and within the SEAL Teams and he is a fairly philosophical guy also, very practical guy, but he has said many times to me that the most powerful words in any language. Are I am
Because whatever follows that tends, if you repeat it, enough tends to have this kind of feedback effect on the on how you are in the world. And it the first pass. It. It sounded to me a little bit like, you know, kind of like internet psychology type thing like, oh the secret or something said which frankly I'm just not particularly have yeah and I say if you kind of like the whole fake it till you make it, like I don't actually subscribe to any of that but in dissecting that a little bit further with him, I came to realize that that
These words, I am are very powerful. I don't think you reprogram your brain just by saying them. But how one defines themselves internally, not just to other people but how he won psychologically, and by default in defines themselves, I think is a very powerful like and depressed people as well as happy people seem to Define themselves in terms of these categories of emotional states. So I think it's it's so interesting that letting
Go and going into this perceptual bubble, which is facilitated, by obviously a really wonderful team of therapists. But also the serotonergic agent allows us to potentially reshape the perception of self. That's, that's a tremendous feat of
neuroplasticity. Right? And I think certainly more work needs to be done. And this is the the Horizon and and she credit Chris left to be a philosopher and Australia who
Has a forthcoming book. It might be out right about now, or
soon within the coming months
psychedelics and philosophy,
as the title of the
book. It's is it might be psychedelic philosophy? It's really close Chris
leatherby, and we'll put a link to it.
Right? And, and so his conclusion in this, it's a really great book and he really plays with the idea. It's like psychedelic experiences come along with a lot of Supernatural stuff experience. It can certainly go along with that. But the idea is, I can't can these
Experiences and including the therapeutic effects, be explained from a naturalist point of view. And his conclusion, is that that changes in self-representation. Maybe the commonality now that could go along with plant spirits and the Buddha and chakras, and whatever your model, you know, system in Jesus, all of that, but it could also be completely devoid of any Supernatural, any religious. And we do, in fact,
See all, you know, all of these varieties. So, I think there's something about this change. In in sense of self. There is seems to be something on the identity level. Both with, I think of the work we did with cancer patients, who had substantial depression anxiety, because of their cancer, and also our work with people trying to quit cigarettes, smoking. I mean, there's this real there seems to be when it really works this change in how people view themselves like smoking, like
Really stepping out of this model. Like I'm a smoker. It's tough to quit smoking cigarettes. I can't do it. I failed a bunch of times. I remember one participant during the session but he held onto this afterwards, said my God, it's like. I can really just decide like, flicking off a bike. I can decide not to smoke. And it's, I call these dutta experiences with psychedelics, because people often like in the Kansas that you say I'm causing most of my own suffering, like I can
I can follow my appointments. I can do everything but I can still plan for the Vic. I'm not getting outside in the sunshine. I'm not playing with my grandkids. I'm choosing to do that and it's like they told themselves that before and the smoker has told themselves a million times I can in it. So it sounds when it comes out of their mouths. And folks will say this is part of the ineffability of a psychedelic experience. Folks. Like I know this sounds like bullshit and the sounds like, but my God, I could just side like they're feeling this gravity of agency.
And which I think is interesting because regardless of the, the debates, on the reality of free will, I think the philosophy of that whether there's, it's ultimately free free will like pure agency. If that exists, which I'm skeptical of, or just the idea that clearly, we have a sense of agency. There's something there, whether it's the sense of agency, even that is the human being has, and that seems to be at
Fundamentally like supercharged from a psychedelic experience. This idea. Like I'm just going to make a decision like normally like you told a press person. Like don't don't think of yourself that way. You're not a failure. Look at all that. It's just yeah, it's like it. And well you can actually in one of these states have an experience. We realized like why God just like using MDMA to treat PTSD and we're going to be starting work with psilocybin treat, PTSD. Someone could really reprocess their trauma in a way that like has
Has lasting effects and clearly, there's probably something, you know, reconsolidation of those memories. They are, they are, they are altered, you know, very consistent with what the our understanding of the way memory works. So the whole idea people can actually in a few hours, have a such a profound experience that they they decide to make these changes in who they are and it sticks, there
seems to be something like that and that's profound. I mean, I think a few moments ago I was
I made us some semi disparaging statements about things like the secret now. Formations. And and the reason I do that with with a, with a nod, to the fact that the people in who are putting those ideas forward are well-intentioned. People is that the neural networks of the brain put language. Last we tell stories, you know, and stories are very powerful, but I think one of the most cruel aspects of the whole self.
Help literature and popular psychology. Is this idea that everything you say your brain and body hear it. That's actually a very unkind or even cruel thing for people who are depressed or anxious to hear. Because if they hear that in believe that and I want to be clear, I don't think it's true that they think that it's very hard to control thoughts is very hard to control thoughts. So somebody says, you know, I can't and then somebody says, well, now every time you say you can't your brain hears that and
Reinforces that that's a very treacherous place to live and language is powerful, but neural networks, the brain and the networks that underlie emotionality and perception and sense of self. They don't change in response to language. They change in response to experience. Yeah, and it just fundamentally you need. There are some prerequisites. You need certain neuromodulators present, like serotonin or dopamine. You need them to be at sufficient levels. You don't need
A drug necessarily do it, you could, you know, you give a kid a kitten or a puppy. Their first getting her puppy and that levels of dopamine and serotonin. I've never measured them but we can be pretty sure that they are higher than Baseline and that
experience will reshape them, right? Yeah.
Likewise with an adult than a certain circumstances. So I think I'm fascinated by this idea that I somatic and a perceptual experience but a real experience of the sort that you're describing.
Yeah, is what allows us to reshape our neural circuitry and to feel differently about ourselves. And I know there's been really tremendous success in many individuals of alleviating depression. I'm treating trauma with these different compounds. I wanted step from the, The Experience, under the effects of the Psychedelic. So the person, they're with your team, they go into this expanded perceptual bubble. If things go, well, they're able to do that.
To a really deep degree. Maybe it's the the relive trauma. Maybe it's the beauty of the their ability to connect to things in the world. Now. I want to talk about the transition out of that state and then the export into life because this is really where the power of psychedelic seems to be in the therapeutic sense is the ability to learn truly learn from that experience so that the learning becomes the default that one doesn't have to remind themselves. Oh I am, you know, they have to do an affirmation. I am a happy person. I am a have, you know, I was thinking Bart Starr.
Person like writing on the chalkboard. I didn't work for him, doesn't work for this other stuff too. But so as they transition out of this state, I know that there's a kind of a heightened. There's a so-called Peak where everything seems to be kind of cascading in at such a level that the person just, they can't really turn it off. At that point. It would be challenging and then they start to exit the effects of the drug. Are those transition zones. Are those valuable much like
Is the transition between a dream in the waking State valuable because you're in a sort of mishmash of altered reality and new reality, right? What do you what do you do to guide? People through the out, the tunnel as they exit the
tunnel and I had to say like this is where we need more experimentation. Really. The clinical model goes back to literally the night late 1950s, and there's been virtually. No.
Ation on let's say, you know, randomize people to we're going to talk more during the latter half of the of the session versus not
versus we have them, you know,
write an essay after their session versus not versus. We have this amount of integration. What's the
discussion in your studies? Are they are they writing or talking to us? They're doing and it's
called, you know, very loosey-goosey, you know, term integration, but for us means
As they're coming back from the experience to sort of five, six hours in, you know, so this is the afternoon, they've been dosed around nine o'clock. So this is like 4 o'clock or so. Just some initial, tell us about the experience. Do you want to not unpacking it? Totally. But, kind of initially just have a little bit discussion before they go home. So, there's a little bit of that, but then that night, their homework is to write something. So it could be, you know, a few bullet points. It could be, you know, 20 pages and we get everything, you know, in that range.
But, you know try not to be self-critical. It's not great. It like just as just to process and for a point of discussion the next day so they write something to come in the next day for a one to two hour depending on the study integration session. Basically just got, let's discuss your experience and depending on what study it's in like what what might that mean for your dealing with cancer. What might that mean for your smoking or becoming a
non-smoker?
So you encourage them.
To Simply take it seriously. And I think this is again, a sort of one of the points that could be the antithesis of what some just kind of social users use. I mean, this was written about by Houston Smith. The Scholar of religion in terms of these mystical experiences that can happen from psychedelics and how a lot of times the attribution to a drug effect is dismissed like the net. Even if one has this, you know, this sense of being one with the universe and it totally like shakes their
Soul so to speak, you know, but the next day, their friends, like dude, you're screwed up too much acid for you who, you know, like, man next time you needed to have a few more beers to like bring that down, you know, like this sort of like, you know, social, you know, reinforcement for dismissing, the experience all, God, you're talking out of your head man, like, you know, even if it's, you know, good-natured, but it's this dismissal. It's not like
You know, what you want to do, you know is tell me more about that. You know, you were crying at one point like in talking about your mom. Let's talk about that. What was that? Like, do you remember that like you are
you doing that follow-up or you? They're encouraged to do that in their own life, with the various people in their
life both. So we do that, explicitly in the follow-up, where we have these discussions and I depending on what the situation is, you might encourage the person to kind of follow up. It's really the
The basics of it is is supportive therapy. It's non-structured. It's, you know, use all that, you know, reflective listening and sort of the humanistic psychology that, you know, unconditional positive regard for the person. But but, you know, I think if you know, if someone feels inclined to apologize to their to their to their sibling, about some things like, yeah, go ahead and call them up when it does something big like a relationship.
Change and be like, sit on that. Two weeks. Don't make any big, don't end any relationship. Don't quit your job. Don't make any big. You
also tell them not to start any
relationships.
I don't remember that ever coming up. What's your, what if it? But I'm not joking. I was
just wondering, you know, it's easy. But yeah, makes
sense. Why you like it? They're dating and they're thinking, like, might be time to take it to the next level show. I ask this girl to marry me. If it did come up. I would say there too. Why don't you sit on that a week or so? Don't get a
Fletcher, sober mind. Don't get a puppy. Certainly don't get for puppies, until your. I have a question about flashbacks. Uh-huh, you know, when it one of the kind of things you hear,
As you know, flashbacks and that that people do people get flashbacks. And if so, what is the basis of flashbacks? The the on the street lore about this? Is that somehow some of the compound gets stored in body fat tissues and then released later like a is that complete
nonsense? No evidence for that. So probably complete nonsense flashbacks are nonsense or the
storage. In body fat is completing the
storage and body fat. So to answer whether flashbacks are
Pleat nonsense, we have to Define it. So I really think these are multiple constructs that are going. It's not the same thing that fall under that term there is a phenomenon that that appears real. That's called hallucinogen persisting, perceptual disorder. It's in the DSM. A certain number of people very small number of people percentage-wise. Have you psychedelics will have these persisting perceptual disorders? Like they'll see Halos around things. They'll see some Trails like
You know, like the afterimages following an object in motion and they'll see distortions and color and it'll be like anything else. That's a disorder in the DSM. It has to be clinically distressing and it has to be persisting over some number of months. And and so very rare, very mysterious, some of the keys to that are.
Amazingly, it's never been seen in the thousands of participants either from the older era, from the late 50s to the early 70s people in psychedelic studies, with LSD psilocybin mescaline, and it's never been seen in the modern era again. Now with thousands of participants at a number of centers like ours throughout the world. So it seems to be something that is for some reason happening and illicit use. So now that brings in okay, is there polypharmacy?
Ecology, you know, because you're drinking during it and you take what you thought. Yeah, what's the dose is with the Purity. But then also what I think is actually even more. So than that what's likely going on is some sort of very rare neurological susceptibility. There is one paper that is a case series of individuals reporting these symptoms and they didn't limit it to the to just people would had hallucinogen history in the amazing thing about this. Is that a number of people
Seemed to have straight up. HP, PD, diagnosis HP, upd, hallucinogen persisting perceptual disorder who have never taken a psychedelic. So it's often prompted by alcohol benzodiazepines cannabis, even tobacco. And and I believe in one individual no lifetime history of any. It wasn't preceded by any of those, you know substance use is so I think it's
I think of it like the precipitation exacerbation of psychotic disorders. We it seems pretty clear through observation that some people with with either predisposition or active psychotic disease, that this can destabilize them cyclic. The same way that a life experience can destabilize those person more easily. I think of it like that. There's probably some pretty rare neurological susceptibility. We have tended going, this goes back to the 80s, you know, clinical practice. It ended up in the
focus on hallucinogen, because
I related to the the psychology of xenophobia. It's always the weird other thing that gets the attribution. You don't attribute to the thing. Like, oh, yeah. Did you smoke cigarettes? Did you drink? It's like, well, yeah, but I see lots of people drinking and not ending up with this. Like you take a crazy like drug and you can get people to believe all sorts of crazy stuff. The biggest example of that is the the cathinone derivative so-called bath salts. And remember, several years back. Yeah. Well, the guy in with, Florida.
That that ate the other guy's face. There's a homeless guy that like literally ate part of someone's face off, like, yeah, while the crazies a lot, while the person was alive and all it took was one sheriff's. Deputy to say, well, I don't know, but I bet it was some of that bass all stuff that's been going on. The only thing,
what it was, it was
the only thing in his sister. Maybe
we could set the record straight for people. What was this? Why would he say bath salts? And was it bath salts? It
wasn't. And so the
Only thing in his talks was Cannabis, which we all know typically people don't eat people's faces off after they gets this, you hungry or what not that, right. So, it's just an example of the xenophobia like today. If you get on Google Images and look up, you know, bath salts, one of the most comment, you know, images you'll see, is this poor guy's face being eaten off. So we're just so ready to latch on just like the people of another culture that we don't know about. It's, it's very easy to assign.
Attribution to a class that you're very unfamiliar with. So I think they decided elex got that attribution with this very rare neurological susceptibility. The way that alcohol didn't. So I think it's not specific to psychedelics, but we don't really know we need, but we look at it and our research have never seen an example of it. But flashbacks can mean a number of other things. I think the most common thing, people experiences, what we call, state-dependent learning its return.
Earning yourself to a similar context. Can bring back the same thoughts and emotions as the experience. So, you know, someone used a mushrooms a week ago. Now they do something like they smoke some cannabis or they or their they take a warm bath or they're simply like relaxed and seems to come out of the blue and all of a sudden these or they follow a thought trail that takes them that reminds them of their in and they find themselves in that same experience again, I think
That's more state-dependent learning. It's not the distressing component that is in and it's typically not perceptual and then another class are just sort of perceptual anomalies within a day or two following the experience, which is not h p PD. Most people have a joke that this is a free trip. Like, you might see a few Trails or Halos the day afterwards. It doesn't last longer than that, and it's doesn't screw you up. Its kind of fun like
Oh, yeah, I'm still seeing some trip. Most people will say so it could mean any of those things. That flashback is.
Yeah, interesting. No, I appreciate you clarifying. That I mean one very common misconception about neuroplasticity is that it's an event and it's not an event. It's a process. And we have no understanding of the duration of that process. However, the experience of any drug or any life experience, right? Even if it's true.
Our a wonderful experience or psychedelic experience, doesn't matter sets in motion, a series of dominoes that fall and it's the falling of those dominoes that we call neuroplasticity. I mean, the reshaping of neural circuits could take years. We don't know. It's the, the trigger and then there's the actual change. And so, I think that some of what you described could be, literally the reordering of circuitry that in some individuals might extend longer than others and there is one phenomenon.
That I've been told people experience and I'm wondering whether or not any of the patients you've worked with or people in your trials have reported this. I've never done Ayahuasca, which I'm assuming has some overlap with the serotonin system, probably hits a
variety of Social and the DMC system. Yes, orally act. That's right. You may of course. There's that. Allow the deity to be orderly.
Right? I should have I should have recalled that. Absolutely well. I've never done it but a number of people I know that have done is
Alaska, as well as people. I know who have done MDMA report, an increased sense of what is sometimes called. ASMR. These autonomic sensory Meridian response X's which is and it's interesting. A lot of people have these naturally and they hide these. These are it's actually something that many people keep hidden to themselves. I'll just ask you if you can do it. So some people are able to pass a like a shiver down their spine or up their spine consciously.
You know, like you can kind of like, I'm able to actually pass a shiver up my spine. I actually learned how to do this. When I was a kid on a hot day. I was standing on a field and Sports Camp. I was like, it's really hot here and I could actually create like a cooling percept cooled, perception. Some people, I told someone this once and then at this led to a discussion of oh I can do it, but I always hid that from people because it's actually somewhat pleasurable and this is a well-known phenomenon phenomenon, ASMR. And some people I know who have taken MDMA therapeutically or ayahuasca.
Will report that they feel great relief from this. They can generate these autonomic reflexes through their body. More readily. Probably I'm guessing because they were able to tune into a kind of deeper sense of somatic self. Now on the internet ASMR, if you look it up, it's a little bit like the basalt thing, but in the other direction like there were people that pay let's just say their accounts on YouTube that have many, many millions of yours of people that will whisper.
Them about. For instance. There's a people that will go listen to. It seems to be women in particular Whispering about, like car mechanics, or something, or about or scratching. So there are certain sounds will do this Whispering tapping finger, tapping and people experience immense pleasure from it. It's not really sexual pleasure. But it's this kind of deep core of its the autonomic nervous system down the
Crowley, what a certain number of people would call Kundalini, which is Annoying Orange scientifically. Whoo. Yeah.
That's right.
Yeah. People who do long duration, Kundalini breathing sessions. Many of them will report later feeling as if they, their perception of self is outside of their head there, right? That. They were literally walk. It's am very uncomfortable for them that they feel like they're walking around with their sense of self extended beyond the body. And this is a neural. This is a clinically describe neurologic for
not have any studies been done. I would imagine that person might actually like with a duck. Oh, what? If they're like, that would be an interesting because it's kind
of in my lab.
I want
to get to, that's everybody could
clear, but they're right projection. Yeah, wouldn't
ya the sense of self? I mean, there's a, there's a well-known phenomenon. It's very few individuals, very sad where people actually avidly seek out imputation of their limbs because their limbs, they feel don't belong to their body. Oh, yeah. This is very sad and fortunately very rare, but also very sad condition. Anyway, I think that the, the core of this conversation that we're drilling into is this notion of reordering, the
Self. And it's, and it's a relief to me to know that flashbacks are not something. That is kind of forgive the term baked in, to the, to the Psychedelic experience. And I suppose that's a good segue to ask about other sorts of drugs. I having said, baked in the Temptation is to go to marijuana or cannabis. But but if we if we could I'd like to just ask about some of the more dopaminergic compounds in particular MDMA. Yeah. My understanding is that
Dma is a purely since that synthetic compound, that you're not going to find MDMA in nature
so far so far, sir. DMT was first synthesized in the lab and then we thought it didn't exist in nature. And then like, Richard, schulte's found it like everywhere. Yeah, actually, yeah. Who knows? A plan out? There might be making MDMA. But right as far as we know, now
know, right, and we'll talk about DMT and it's sources within the body, but MDMA could exist in elsewhere.
R but has been synthesized. And my understanding is that MDMA leads to very robust increases. In both, dopamine and serotonin simultaneously, which from a from a neural networks perspective is a very unusual situation, right, normally? Because dopamine puts us in this external acceptive looking outside ourselves, seeking things in the world, beyond the skin, our own skin. And dopamine, excuse me. Serotonin tends to focus Us in word. Those are all
Mutually, exclusive kind of neurochemical States. Although they always a different levels. So why would it be that having this increased dopamine and increase serotonin would provide an experience that is beneficial? And how do you to accept you can describe it? How do you think that experience, differs from the sorts of experiences that people have on psilocybin or more serotonergic agents? Just broadly speaking?
Yeah, Yeah. In terms of that.
At that balance, in terms of the the effects, generally, on serotonin and dopamine, I can only, you know. Speculate, you know, like sort of is that dopaminergic component necessary for let's say, we know that the amygdala is less reactive during under acute effects. And that may play a role in. There's less sort of control, from, from the amygdala, in terms of like one's experience of memory. So
Maybe part of this sort of reprocessing, this reconsolidation of these memories in a different way where the amygdala is not like going crazy saying freaked out like, you know, fight or flight. What I should
have said, it seems like MDMA is being used clinically. Anyway, mainly for trauma, not just for depression.
Although part of that. We really don't know and maybe that MDMA is great for depression and some of these other in a maybe that and I'm going to be looking at the soon. That's psilocybin is great for treating PTSD. A lot of underground therapist. Say that underground psychedelic therapist. So we don't really know you my underground. Oh because they're doing you legal, you know, but more like, you know, a professional therapist would it just illegal and this is a kind of a growing thing so we don't really know which
It. It speculating but it may be that MDMA for a broader. Number of people is better for for trauma because the chances of having an extremely challenging experience, what I call the bad trip, like really freaking out is much lower with MDMA. People can have bad trips, but there are of a different nature. It's not it's not sort of like freaking out because all of reality is sort of shy
A touring, and it's less of this. It can take so many forms with the classic psychedelics. But like, typically, you'll hear something like, I didn't know it was going to be like this no matter how hard you try to prepare them. That like, this is like get me off this, your trellis to your syllabus T cells have an iWatch. Yeah. Yeah. And just this sense of like I'm going insane. This is so far beyond anything I've ever experienced.
It's scaring the shit out of me. I cannot have a toehold on anything even that I exist as an entity and that can be really, I think, frankly experientially, that's kind of the gateway, to both the transcendental mystical experiences that the sense of unity with all things which we know our data suggests is related to long-term positive outcomes.
Wait, I want to make sure I understand sir you saying the bad trip can be related to the
the transcendental
experience, right? I think those are both speculating but you have to pass through this sort of like reality shattering including your sense of self and one can handle that in one of two ways. You can either completely surrender to it or you can try to hang on and if you try to hang on it's going to be more like a bad trip. So again, I wish there was more and hopefully there will be more experimentation. There's a lot going on here in the Black Box. In terms of the operant.
How you are, you know, within yourself choosing to handle like, letting go, you know, and eventually we'll be able to see this in real time with brain Imaging. Ah, there they are surrendering to the Psychedelic experience here. They are trying to hold on, but we're not there yet. But I think it's a new clinical observation, seems pretty clear that something like that is going on and certain drugs. Like DMT, smoked DMT can be so strong. The reason I think that can be so extraordinary.
You can compare the others because it like forces, people like there is no choice that he never done it. I
was told that DMT is like a high-speed locomotive into the Psychedelic experience and out of the Psychedelic experience. Yeah, and there's no ability to hold onto the self while you're in the kind of peak phase. Is that
correct? A lot of people say that but some Terence McKenna who's kind of the classic Bardon DMT effects, he would say the sense of self was intact, but everything else
Sensorium and what you navigated, what you oriented towards everything else change basically, but it's hard to win. Everything's changing hard to say, like, what is the self that's changing. What is the rest of the world? Well, and
languages is totally deficient to describe experience. Anyway, much less on a psychedelic. What is McKenna's background? Like, what is his qualification? For being this, as you referred this part of DMT? And
so and we're talking about Terrence and there's also the brother, Dennis.
- who am I know whose can only imagine what? Yeah, it's their brothers. Like Terrence has passed away years, couple decades ago now, but he's sort of the one who's known as being a Bard. And you can find hundreds, if not thousands of hours of him on the lecture circuit in the 80s and 90s on YouTube, but his background was really, oh, gosh. I don't recall what his college degree was in, but he basically when he was like 19, he traveled to South America and
And actually on the initial trip, with his brother who was even younger than him with some other friends and just in search, for in DMT, snuff that they had read about from in the Harvard archives, from the work of schulte's from a generation before. But they had discovered all of these mushrooms growing that down there. The psilocybin mushrooms, would they recognize? And just took a lot of mushrooms and and and talked about
It talked about and Terrence was basically a very intelligent very well-read and and literature and culture person that could be was sort of the next Generations. Tim Leary someone who could really speak. Get a little closer to the magnitude of what the Psychedelic experience was like for people and he serves like Leary somewhat of an advocate. I mean, he would tow people folks. You could see, you know, the equivalent of the UFO landing on the White House.
On like it's right there. It'll take five minutes. It'll Shake everything in your reality. You know, he would sort of good people into doing
it. Well certainly science and clinical medicine is are just but two lenses with which to explore these things in life. But what part of the reason I ask is I feel like, you know, in the world of health and fitness, you have this very extreme condition of like Arnold Schwarzenegger, xand.
D Builders who have like two percent body fat and they look like to most people they look kind of freakish
especially now, right? I'll especially now, especially now. Yeah, and yeah, Nate on Rural. Look, yeah. Like yeah, regular exactly back in his day. Yeah. And you have
contortionists, who can put themselves into a small box and wrapped themselves into a pretzel, but from those two, very extreme subculture practices that I don't know anything about contortionism really, but except that they get really bendy the
But it's a community that included a lifestyle practices and nutritional practices. And in drug practices, from those very extreme subcultures. There's been an export, which is that, you know, weight training is healthy, right? The general public is done that or that yoga is healthy. So contortionism to yoga, Etc. Hmm, and I feel like a similar thing is happening in the realm of psychedelics where it was.
Leary and Huxley, I mean, I like, I'm from the Bay Area. I'm not far from the Menlo Park. VA, where One Flew Over the Cuckoo's is basically a song, right, Ken Kesey. And those guys and, you know, the there has been an attempt at creating this movement toward openness about psychedelics and their positive effects. This has happened before the difference is that now there are people like you inside the walls of the University or publishing peer-reviewed studies, and things of that sort. The reason I asked about McKenna was
You know, it seems like McKenna and his brother are, but, you know, it's just two of many people. Michael Pollan, Etc, who have no real formal training in biology or psychology. The other guys who were at universities lost their jobs. They were actually removed from places like Harvard and other universities for their kind of cavalier Explorations, right? And
now things are kind of returning. So in the same way that
Thing led to
weight training and every corner gym. Yeah. Men, women and children, and contortionism is one extreme, but people generally think that yoga is a pretty healthy practice right there. These are matter of degrees, right? And now here you are inside the the the walls of a very highly respected University, Johns Hopkins, you're on the medical school side and undergrads are in the med school, which is a you know, serious health
Institution, you know, the question is to me, you know, what are the, what are the valuable export? Right? And where does the extreme lie? I mean clearly there's a there's a problem with tinkering with reality through pharmacology and there's a benefit. It sounds like to tinkering with their reality, through pharmacology. And what's, so striking To Me is This is the
Elements of a typical experience, a typical representation of the self. So for the, for the average person, right? Or for kids, that are hearing this kids that are in their team. That's right. Yeah. What are the I want to talk about? What are the dangers of psychedelics is something. You don't hear a lot about these days and it's not because I'm antipsychotic at all. But what are the dangers, right? If if a kid or adult has a predisposition toward, let's say,
Psychotic thinking, right? Or auditory hallucinations or, or is on the Aspergers, side of the autism spectrum. Is there an increased risk of bringing the Mind into these states? Because it sounds like a very labile situation. So, could we talk a little bit about that? And are there classes of these different drugs, whether or not be MDMA LSD, or DMT? That are that you think are particularly sharp blades and therefore need to be
ODed. Particularly
carefully. Yeah, so these can be profoundly destabilizing experiences and ones that, you know, ideally are had in a safe container, you know, sort of where, where someone what are the relevant dangers and what can we do to mitigate those? So there's two Biggie's.
One and I've already mentioned its people with very severe psychiatric illness. Not not depression. Not anxiety. I'm talking about psychotic disorders like schizophrenia or Mania as part of bipolar disorder. So and diagnostically this is shifted. So it's a little hard to say how many people today with bipolar would have been labeled as schizophrenia back in the 60s when some of those early research or just clinical observation was done. So
Seems very clear that folks with a predisposition or active disease, they could be destabilized. And so some of the cases that we know, of always think of Syd Barrett, the first singer Pink, Floyd seems pretty clear. Although I think the family, what
happened there, so I should be sorry. Pink, Floyd fans. I've never that songs are just really long.
Yeah, you're more of a punk guy, right? Yeah. So I've got my foot in a lot of Worlds. Definitely, in part in the Floyd world, but
But he basically went crazy early on, he did it seem, I don't think his family ever admitted it, but he developed schizophrenia classic pattern and and he was doing a lot of LSD but you know, like a lot of these cases it looked like he was showing all of the signs of, you know, some some hints of that. He had that susceptibility before and off.
This is hard to disentangle. What causes what because when two people typically not always, but develop when's the modal period for first break, its adolescence, early adulthood. Yeah, and when two people start, playing with drugs, same exact time period. So we can be hard to disentangle, but it seems pretty clear. Now. I should also say there are cases of folks with schizophrenia that say psychedelics have helped them. There's anecdotes for everything. The people around those
schizophrenic say it's help them. I don't know. Is when it's good.
The phrenic say things, you have to know. I mean, we don't with all due compassion and respect for schizophrenia. It's a disorder of thinking. So if they're saying it helped them
have. Yeah. Can you trust them? Yeah, I wouldn't be surprised if there was some kernel truth in some cases, but they're just so it seems very clear that the other side is there too and that that there ever is a therapeutic potential there for those disorders that that shouldn't be the first thing on our list. We need to learn a lot more because of the
Of rest before we start doing research to see if you know psilocybin and can help with schizophrenia. Like I don't think that that may never be the case. But even if it is, you'd have to be even more cautious and figure some more things out first, with some of these other disorders.
What is it seems similar? Bipolar disorder. Can it be exacerbated by these?
Yeah. Yeah, and it's, it may be that sort of the manifestation of people having prolonged psychiatric issues after
a psychedelic experience as a typical is that is when that happens it maybe that's that might be more like a manic episode than a psychotic episode and that can be a blurry line and it's
The folklore is that young people go on a trip and they never come back. That's clearly not the case. Because, you know, the drug is metabolized like for anyone else and the next day. There's not, you know, it's
really not even sure circuitry. I mean,
right? And they're still and I really do think, you know much like the positive experience, you know, long-term effects that, you know, this class of problems is related to like the to the experience and the destabilization that can happen from
That from that experience, if it's not in that in the right container. And again, like these people are susceptible to, you know, some people with that psychotic predisposition, they lucky to be born to a great family, stable environment. They maybe never have a full break or the one that they have is not nearly as bad as what, you know, someone that use who's homeless and is coming from all kinds of Early Childhood trauma. Like the disease is probably going to be far worse, you know, so,
So, you know, the site having a psychedelic experience is like one of those destabilizing experiences, you know, so excluding out. Fortunately, it's really easy to identify those people and we even are on the side of Extreme Caution by eliminating people with like say a first degree relative and some studies. Even a second degree relative, given the heritability. There's some increased chance if your brother your yeah, so, so in an abundance of caution, even limiting that I think,
Julie, if it's approved for use FDA, you said we could dial back on that as we learn more? I think it's again over overly cautious which is but you're doing the early stage Chloe. Yeah, sure the appropriate place to start this point in time. But you know, if you give a skid or another structured psychiatric interview with the clinician seeing, now with this person for a few hours to delve into their history and like you can very reliably determine at this person has either, you know, psychotic disorder.
Or bipolar disorder or a strong predisposition. So that's you know that you can screen for that. And that's how you address that the far more likely danger is the bad trip. Anyone can have this the most psychologically healthy person in the world. Probably Jack the dose high enough and especially and in a less than an ideal environment, you can have a bad trip. You can you even get it in an ideal environment, like ours at a high dose of around 30 milligrams of psilocybin after, you know, the best preparation.
And we can provide about a third of people will say, essentially, at some point. They have a bad trip, you know, we
need some point within, the, the entire Journey
right now. They could have one of the most beautiful experiences of their life. Sometimes like a couple minutes later, but at some point, they had a sense of strong anxiety fear losing their mind feeling trapped something like that. Now, typically, when people have that in the, you know, when they're just taking on their own, like a lot of things, they're fine, they get through it.
You know, they're more likely to be better off if they're not having to navigate the streets of Manhattan that, you know. Or and if there with you know, other people with friends better that those friends aren't also dealing with their own psychedelic experience, but probably having some friend of any type but what other on there is better than having nothing. So very dependent on context and so the tough thing here that in conveying to the public is that
A lot of folks will say man. I've taken psychedelics hundreds of times and this is like your fear-mongering and you know, there's no, you know, you're exaggerating the danger there. So I want to say it is a typical but sometimes and I have a file folder that grows larger every year of these cases either in the medical literature or from the news of people that freak out on a psychedelic and they get hurt, if they die, they run into traffic.
Eric, they, they fall from a height, whether they thought they could fly or they just fell like they you can do when you're drunker and you're intoxicated on any substance. Sometimes that's that's unclear or gosh. One of the craziest cases was a kid like an 18 year old or so in Oregon several years back that just he even wrote about, I want to take the biggest you've done mushroom for. I want to take a heroic dose. The biggest house I've ever taken. He ended up just totally out of it, ended up in
Neighbor's house. He was just totally disoriented disconnected from reality in the cops ended up killing him. And it was just tragic obviously, and over use of force, in that case, because he was actually naked at the time, this naked like a hundred and twenty pound. I think as a recall kid that ended up dying but well, it's
analogous to the, you know, the reason I use the examples of like, bodybuilding culture. I mean people there have taken excessive amounts of antibiotics, and diuretics and died. Then the contortionist culture people to put themselves in a little Plexiglas box has to do, you know
At the extremes, you're going to get deaths and at the extremes and as, and one of the extremes is the sheer number of people with different biological makeups taking the same drug. And so you can create extremes through numbers. You can take extreme. You create extremes through dosage, right? It seems, well. This is why I'm such a fan of, of the fact that people like, yourself are doing clinical trials inside the walls of universities. Not because
I think that psychedelics only have utility in those environments, but because it's so important toward creating their transition to legality and understand what legality means for a compound like this.
Right? Right. What bottle right. I mean, again, I will stay with the
anabolic steroids. There's now testosterone and estrogen replacement therapy hormone replacement therapy is a common medically approved practice, but that's vastly different than people taking their own stuff for dying or deciding how much they need to.
Take right. Like we said, there's hope there's yoga and there's contortionism in a plexiglass box and, you know, thinking of Houdini or something. So they're these are a matter of degrees. Speaking of dosage. I definitely want to ask you about micro dose versus standard or macro dose.
Tell me,
tell me that I'm wrong, but I'm always a little bit, I sort of a little micro cynical if you will about this term microdose. And the reason is that many people that I know who talked about micro dosing are taking dosages of compounds that work at Mike, that are very powerful at microgram levels. So, the word micro I think can be a little bit confusing to people because my
Dos implies less than something. It's a meanie dose, right? And yet some of these compounds are tremendously powerful at microgram concentrations. So, what it constitutes a microdose and what is the value of so called micro dosing, if any and how does it differ from standard or what? I can only assume is called macro dosing.
Yeah, and so LSD would be the prototypical.
Example of that super potent.
How much might have? What, what size dosage of LSD will lead to hallucinations and kind of standards are the entry
point for psychedelic type effects, which may not involve hallucination. Actually, most classic psychedelics. Don't lead to True. Hallucinations as defined in Psychiatry of, you know, see thinking you're talking to the person. That's not they're saying the Pink Elephant. It's my straight-laced tracers and things like right and perceptual blending people never get that.
At a very high dose. So I think more broadly in terms of the Psychedelic effects, which isn't just perceptual unless we get into the level of as you were alluding to earlier a broader definition of perception, like ones models of the world, the model of the self, you can, you can consider all of that perception in terms of, you know, truly not sensation, but perception, the construction of a putting together a reality, so yeah. Yeah. Yeah. Yeah, so de psychedelic effects.
Are typically considered star for LSD around a hundred micrograms. So 1/10 of a milligram is a hundred micrograms and the sound taking a
hundred micrograms of LSD. They on the nowadays, people might mistakenly refer to that as a micro dose because it's micrograms, but that's actually a macro dose of
LSD, right? They might and that's one of the most common mistakes or situations that people get into with micro dosing as they intended to be a microdose, but it ends up being a full-blown, you know. Do
Now, people do when they're working with LSD in their micro dosing. Those shoot for something like, say 10 milligrams, you know, something in that range, 10, 20 milligrams of LSD. So, you know, a tenth V something of kind of your entry-level psychedelic dose people's ability on the street to do this and I say the street as if they're on the corner, but anyway, like outside of the medical profession to do this like, varies as you can there
not measure impurity or molarity, or things like that.
We and there's ways
to do it. So even if you don't automatically know the dose, that's in like the blotter paper of acid, one could at least get a sense of like, yeah. Having one of those tabs is one of those hits is is a psychedelic experience. They could do something like, put it in water. It's a hundred percent. Aqueous soluble. You can vote, you know, make sure it all gets into solution and then volumetrically measure. It's going to be homogeneously distributed. So you can you take one tenth of that volume of water, or after it's fully dissolved. You know, that, whatever you started.
You
can have a tenth of that do so the people that are more sophisticated. Well, do things like that and when they're working with mushrooms, they'll grow a bunch of mushrooms, and then they'll say, put it in a coffee grinder. I'm not telling people to do this, by the way. I'm just describing said, don't do this at home, but like, grind it all up. So it's homogeneous because you can have like, you know, sort of taking, you know, to caps and a stem. Hey, this two caps in the stem that, this buddy takes is has a different potency than this to caps and a stem that the other buddy take, so people that are kind of in the
No, will grind it all up into a homogeneous powder and they'll pack it into whatever size capsule and they'll know that. And again, even if they don't have sometimes, they might have a buddy that will sneak it into the hplc at their, at their job or whatever. They have. Not your life, not mine. Like that's never happened, seriously, never happened. But, but but they'll, at least know that, hey, I've got a sense of what, two capsules do. I've got a sense of what five capsules do and so but in reality like that's not what people do that.
Take a piece of blotter paper and then get a tiny little pair of scissors Swiss army knife, pair of scissors and I'll cut up the tab of acid, which is like, you know, a quarter inch square or something and they'll cut it up into little pieces and it's like, oh my God, you have no idea like if it's equally distributed in that media.
Yeah, and we can chuckle about it and but to me, one of the reasons why this experiment around psychedelics, this cultural experiment and this legal experiment.
We're seeing this now, but this was all attempted once before in the 60s and 70s. The difference was, it was all out in the street. The people in universities who were dabbling with the stuff lost, most of them lost their jobs or were asked to leave through, you
know, they lost their funding for This research service animal and they had to move on to other topics.
That's right. Have so these are precarious times me worried where to we're in a key moment where everyone assumes that this is all going to be legal in a few years, but I think that that
a premature assumption yank lie, but and I'm and let's touch on the legality and some of the things that are happening now, but
What is micro dosing psilocybin versus the sorts of dosages that you described before in the tend to 40 milligram range? I've heard of people taking one or two milligrams of psilocybin every day, as a way, to quote unquote. And for those listening. I'm just making air quotes with my fingers increase plasticity, which is it, which is a term that I personally loathe because what does that mean? I mean, you don't really want your brain to be plastic because you need to make predictive. You need to maintain your ability to
Predictions. Yeah, I mean we're kissing
ass like prediction your you need models of the world you need here is sticks like
plasticity is never the goal or bit. Plasticity is never the goal. The goal directed plasticity is the goal right learning a language reshaping your experience to a trauma. Altering the perception of self, but plasticity is a process. Like
is it's a friend, Nia is a lot of plasticity. Exactly. Right right.
Amanda might even be theirs.
One theory that it's extreme ongoing plasticity and that's why people never create stable representations of anything. That's so kind of minority view out there. But so what's the business with micro dosing? And is there any clinical evidence or peer-reviewed published evidence that it works quote-unquote to make people feel better about anything.
So micro dosing is is the aim of taking, again, something around a tenth of, what would be sort of
An entry-level psychedelic dose for whatever compound. So, so like, yeah, with silicide usually people almost never people have like, pure psilocybin. Like one milligram psilocybin would be in the range of microdose. More likely people are going to have, you know, mushroom. So like something like half of a gram of mushroom. I know people
their daughters ran every day. They're doing these every day. It's like in there like the same way that I take. Like, I'm personally, I'm not recommending other people do this, but I take some, I'm a fan.
Of L. See L carnitine lately. I've been kind of experiment with a little bit, which is not a psychedelic compound by take it every day and they're taking their that's their social science every day. That's their supplement. Yeah. So,
so yeah, if the claims are in their number of them, there's two general ones, one is sort of acting in place of the ADHD treating drug. So the psychomotor stimulus. So like a better version of Adderall, the other claims are essentially a better version of that.
Traditional antidepressants a better version of
Prozac. So we were taking both for attention deficit, and for
depression. Yeah, and the aspects of those disorders that, you know, we all have a degree of in just like, amphetamine is going to increase the focus of at the right. Dose of anyone who takes amphetamine pretty much you, whether your ADHD diagnosed or not. The idea is that you know, that there may not be a necessarily a clear divide between the
Therapeutic need and you know, positive psychology, you know, even improving mood and focus, you know, you know, so it's not necessarily correcting, you know, ADHD, but improving Focus to supercharge, you know, your life. And so those are the claims I am.
So none of the peer-reviewed studies that are have much credibility. None of them have shown a benefit and they've tried. Now, there were there is only at this point, four five studies that and I think for things like this, you really need double blind research because the effects, I mean, there was one study done in Amsterdam where people knew they were taking psilocybin truffles. Basically, same as mushrooms and we're like the roots, the my Celia, my own dosing them.
Making of what would be considered a microdose and then doing some some cognitive measures before, and after, and it's types of thing that, you know, like a lot of cognitive measures are measured on the order of reaction time and milliseconds. I mean, and the types of effects you get, as you could imagine are ones that like would be, you would totally expect. Could be there from either a practice effect or, or an expectancy effect, a placebo effect. So, you know, for something like these
Aimed, you know, you can imagine a sort of an increased Focus, you know, enhancement of cognition. These are like going to be more subtle effects that you really need a good Placebo control for the handful of studies that have done that have shown. They have ranged from finding no effect whatsoever to just a little bit of impairment like impairing someone's ability to do time estimation and production tasks. So you want an accurate sense of time.
At least, if you're navigating in the real world, it's different. If you're on the couch on a heroic dose for therapeutic reasons where you're safe, but if you're crossing the street, if you're getting a in your work life yet, which is why the way people are claiming to you know, use that helps them be a better CEO like you want an accurate sense of time. So if anything it is suggest that it makes it a little bit less accurate and and there's evidence that someone feels a little bit impaired and they feel a little bit High.
Hi, so terms of you know, you call that abuse liability and research not surprising. You take a little bit of a drug that can result in a some type of a high need to take a little tiny bit of it. You'll feel a little bit high. So none of the so far. No Studies have have shown, you know, any increase in creativity enhancement of any form of cognition or sore, a sustained Improvement and mood now,
No Studies have actually looked at the, the system of micro dosing that the aficionados are claiming. And there's a couple of models out there. But, but folks, like Paul, stamets and others, they'll have particular formulas there. Like, you need to take it one day and then take so many days off and take it every four days. And I don't want to get into who's model is what? But it's always something like that. Some pattern of use, usually not every day. And and the claim is that it's not just, you know,
Sometimes people get benefit that first time when they take it, but they really say you need to be on it for a while like a few weeks in, you may start to notice through this pattern of of using it. And you're feeling the benefits on those off days like the three or two days in between your active doses. So, those are the claims again. We don't know that there's any truth to that working but Studies have not been done to model that. So that's a big caveat. We as a feel as if we as the as the
Scientific field have not done the studies to really model. You know what the real aficionados are claiming, you know, you know where the therapeutic benefits come from that said, it's, it's almost assuredly, there's a good amount of placebo there. But but the caveat to that is like, almost everything in medicine or Therapeutics. There's and is going to have some degree of placebo. They leave
effects. Are I have a colleague at Stanford. Alia crumb who has published really?
For work on belief of facts that show that essentially give the same milkshake to to people. You are two groups of people. You tell them that one contains a lot of nutrients, the other as a low calorie shake their there, the insulin response
amazing varies
dramatically between the two or two people, two groups rather doing equivalent amounts of physical movement, and you tell one group, that it's going to be good for them and help them lose weight and they lose on average, 8 to 12 pounds, more doing the exact same.
Patterns of movement. So and I think that these belief effects boil down to all sorts of kind of network-wide neuromodulation things of that, sort of.
But the work at Harvard suggesting that even if you don't have deception you give a placebo and say this is a sugar pill right, you know and tell them that right? And it could still treat things. I think irritable bowel was the first thing they looked at, right? And so there's a huge there's a reality there, right? There's a necessity in developing drugs to make sure it's not only that, but it, but in the actual practice of Medicine,
Hopefully, what you're always getting is some underlying direct efficacy. Plus the placebo that enhances at now, it could be that. This is the real question is, is the micro dosing are those claims? A hundred percent Placebo or they only part Placebo and part real, you know, quote-unquote affect. My bet is and this is totally based on anecdotes that, I think there is probably a reality to the antidepressant effects. I find that more intriguing well because of
The suffering with depression, right? Even if it's an it wouldn't be as interesting as I think what we're doing with high-dose psilocybin or psychedelics to treat depression. It would be if this is developed and there's a reality, it would be more like a better, you know, perhaps a better SSRI a better Prozac which are similar or tools. Then fewer tools in the toolbox and it shouldn't be that surprised I even before the as a going back to the tricyclics and the MAO inhibitors going back to the 50s.
He's like augmenting extracellular serotonin in one way or another.
For many people leads to a de reduction in depressive symptoms. It wouldn't be that crazy for chronically, stimulating, a subtype of Serotonin receptor that you have an antidepressant effect. So, I think if I had put my bets on it, that there's if there's anything real, it is in that category, although I'm very open to like maybe there is something to the creativity to the, you know, improved cognition, which covers many domains in and of itself, but my my greatest hopes are on
The on the antidepressant effect that said, in the big picture, I think all of the most interesting thing about psychedelics are the heroic doses. I mean, the idea you can give something one, two, three times and you see improvements and depression months later and in addiction, you know, over a year later and with these, you know, people dealing with potentially terminal illness. I mean, it's too. I mean, I'm interested in big effects and I don't think you're ever going to get the really big effect. There's also,
Some concern that almost all of these common Psych, the more common psychedelics, even County MDMA, they have serotonin to be Agonist effects and agonizing serotonin to be, has been shown to lead to heart valve formation problems, morphology issue, so valve allopathy. And so, this is why fen-phen was pulled from the market. The diet drug. Yes, very effective Central. Right, right. And it
Is the the portion of that combination that had the, the serotonin to be activity? That was the problem. And so we don't know. So all of the, the toxicologists I've ever spoken to about this. Would, you know, say in cardiologists say like look, hey if there was some concern there, it's not applicable to the whole idea of you, taking something a few times therapeutically within a lifetime. But the idea of taking something like, you know, twice a week for
For years, I mean, even the the hippies back in the 60s weren't doing that. Right? Like, there's not even these naturally and even if they even if there was some heart valve disease problem, is that stemmed from psychedelic use who's connecting those dots that's not showing up in the clinical charts for anyone to figure out so they're in. And just theoretically, there is more of a concern if something's going to happen with with heart valves. It's more likely that that
Those issues would arise when someone's taking these things. Like yeah, let's say twice a week for the next five years. And so I do want to throw that out to people to really consider,
right? Yeah, it's something I hadn't heard before that in micro sounds safer micro dosing as opposed to heroic or macro dosing and yet unless an in the context of your lab and other labs doing similar work, you've got this people checking blood pressure. You've got people that are really monitoring your psychological and physical safety. When people,
Are out there micro dosing. It sounds like there's a potential either, through this serotonin, 5-ht to be receptor or other mechanism. That there could be some common cumulative, negative effects. The and I think that's in a really important consideration. So I'm glad you brought it up. What about kids? So the brain is very plastic early in life. It becomes less plastic as we age, although it maintain some degree of plasticity throughout the lifespan.
The year 25 at the year 25, but rather the age 25 years is sort of an inflection point where the rigidity of the nervous system seems to really take off. Of course, people don't wake up on their 25th, birthday and find they have no neuroplasticity. Whereas, the day before they had a lot. These are, you know, it's plus or minus whatever. It is a year or two, but depends on the individual. However, the big
The young brain is very plastic and I could imagine there could be great risks, who knows maybe even benefits, but I'm certainly not thinking about those. I'm mainly thinking about the risks of for young people. Taking psychedelics. Are there any trials? Looking at people in clinical trials? This would be under the age of 18. Has anyone explored this in a rigorous way? Given the potential to exacerbate, psychotic symptoms.
Bipolar symptoms and some people is their heightened risk of that. What's the story with age of use and psychedelics? For therapeutic
purposes? There is no formal research. Although I there's a very high chance that there will be and so this is one of the very interesting things. Folks may not realize or appreciate about the FDA approval process. So the FDA already in multiple instances has signaled that there they want to see those studies before. Well, not not.
Before it's approved as necessarily as, you know, for for adults, but they're going to eventually want to see in fact, so that the maps group that's developing MDMA for PTSD.
They've
already signaled, that that's kind of a fun list of interest, and there's even some incentives and that in the FDA Pathways for for incentivizing folks to explore that that use and young people. I know in some of the work that I helped with
In pushing psilocybin into phase phase, 2B, clinical research, the FDA, you know, said, well, why can't you give this to kids? It's like, are you aware that the pression is a problem with, with adolescents? Like, you know, like in. It's really interesting because this FDA is very concerned about pseudo specificity. We idea that fun to do, suppose, you put out a drug and say, oh, this is good for me.
Men, but not women. This is good for black folks, but not white folks. And now sometimes there's a very good rationale for that. Like, when we're talking about hormones and for a specific, you know, for men versus women and there's certain, you know, issues, you know, you know certain disease States like maybe sickle cell anemia. That's more relevant a sex things. Yes, exactly, you know, but absent of something that they're very concerned about saying, oh, this is for this type of person, but not that type of
Person, so age is one of those things and also this recognition, you know much like the emphasis at NIH with you know, with you know, with rodent studies and human studies at like you can't just say you're studying man or just went you need a rationale if you're only stuff. Okay. Yeah. To be clear to people, there's no,
it's a recent swish, but there's a stipulation in every federally funded grant that both sexes. We don't refer to gender in scientific studies unless it's a study of gender per se. We refer to sex
Meaning biological sex. So that there's a stipulation that in order to receive and continue received funding, you have to do studies on both males and females of that species including
humans. And at least lie, even if you're not powered for it, at least looking at that in exploratory analysis, like as a grant reviewer, I'm charged with looking at, you know, did they address like sex is a biologically relevant variable? Any does the thrown in there? Because
the same drug have different effects in males versus
females, right? And you cannot
Look at the trends. Even again, if you're underpowered to look at those between subject type
effects, which is a great shift that didn't exist in, you know, ten years ago. It sounds like we're both on grants panels as study section members. You didn't have to do that. Now, it's a, it's an important biological variable. If you don't look at that, you essentially won't get your funding
and age is a similar thing. So it's the whole idea like man, if something could help kids, like what's the rationale? So I think there's going to be now, obviously you're going to have in those studies.
At least just as much probably more. It should be more, you know of a Kasha cautionary approach. It's probably going to be you know would certainly whatever disease states are looked are going to have to be probably treatment-resistant at least as a first step. You know, Jesus. Try - yeah. Yeah, and so, all of that in the mix, but hey, you know, if this stuff really helps people, you know, that are 25 or 30. Like, what's the rationale that it won't help a younger person?
You know, and there's can these generic kind of concerns about the developing nervous, system is more susceptible to problem. I mean Cuts both ways because it's also more plastic generally and adaptable may be resilient injury in certain ways. But you know, you hear the rhetoric about kids their brains and drugs. And it's like the developing brain is a special concern. So yeah, but I think we're going to be seeing research eventually.
That's interesting. I went to the high school.
That is Infamous. Sadly gun high school for having it. The highest degree at least at one point of suicide suicide rate. Wow, um and a lot very large number of suicides. This was written up in the in the times and elsewhere.
He's a very academically successful school. It's a very academic demanding
school to the point where they've restricted. The kids will meet often 6:30 a.m. Or 6 a.m. Before school for study groups and things of that sort that. So some of it may relate to that.
At. But I have to say that even prior to all that academic pressure. When I went there. It wasn't the pressure wasn't like that. It you know, we had an unusual number of suicides for whatever reason and, you know, and so the idea of kids being prescribed and when I want to be emphasized, prescribed not just using, but prescribed psychedelics for therapeutic purposes. I think might make some people bulk, but the idea of
Kids killing themselves should also make people balk. And so I'm relieved to hear that. There's going to be a rational scientific safe, clinical trial, based exploration of this. I want to ask you about the current status of these drugs and compounds. I'm pretty active on social media more. So on Instagram than on Twitter, but as I have been on Twitter, a little bit more recently, I've noticed
That there's a lot of dialogue around your account and other people's accounts around a couple of themes related to psychedelics. First of all, what is the status of the transition to legality for for prescription purposes. So medical doctors MDS. Prescribing. It legally for therapeutic purposes. That's the first question. The second question is, what is the status as it relates to possession and criminal charges? So for a long time,
I lived in Oakland where we were one day told not to long ago. It is now quote-unquote decriminalized is what I was told. Double-check people. But what does that mean? And then the other issue and the third question we can parse these one by one. Is this issue of let's just say I'm aware of a lot of investor dollars going into companies that are essentially companies focused on psychedelics as Therapeutics or psychedelic.
Generally, I have to assume that they are investing in anticipation of a shift in the legal status. And there's a lot of interest now, like will psilocybin become a taxable thing, just like marijuana. So let's start with the question of like, what is going on in the US legally. Is it illegal to possess and sell and use these compounds. My understanding is you can still go to jail for having
In these compounds in your possession or for selling,
right? So even though it's a the, the legal landscape is very different than with cannabis. There are some similarities. So one of the similarities is that regardless of what local Municipal, you know, with city or state has
decriminalized
and that that word itself can mean many things. So the devil, some some forms of decriminalization is close to what folks would call legalization and others.
Like pretty weak, you know, just saying, we suggest that the police make it, their lowest law
enforcement priority that's like, throwing they turn the other cheek kind of
right, but even that the cops can still choose to, but someone can get, you can
get pulled over for one thing. Searched. And then by definition, if it's illegal and they find it, right? They have. They have to do something
about and that'll probably be determined by, you know, like both judicial precedent. Is it going to be thrown out and just the local prosecutor, you know, even before? Like, are they going to choose?
Even at post-arrest are going to pursue to really, you know, go after those charges make those charges stick. So, I think that's still in play, and it's going to depend on the municipality. But like, cannabis federally. These are all schedule one compound, which means they're illegal in, which means they're illegal. The caveat to that. Just as always been the case. Since prop, 215 in California with cannabis and 96 is that hey 99% of drug enforcement has done at the local and state level the DEA, which is
Federal level of law. Enforcement is a tiny fraction of the arrests that got me. Most people are arrested for any drug are done by local or state level authorities, but it's still technically, you know, illegal and so you can and they could potentially depending on the ambiguity, local law. They even those local officials could charge you with a federal crime. And theoretically, the feds could always come in now.
Now although you'll you know, again a similar, you know, case with the whole cannabis history. It was the feds came in in the early days, but the folks that were basically highly visible. They went after Tommy Chong for selling bongs. But you know, I remember him being on The Tonight Show one time and I think it was back in the jail in today's uses but all along Santa, Monica boardwalk at like every Shop sells bongs. How did you go to prison for a half year for pawns? It's because he was and there because he's famous because he was Tommy Chong.
Long and and there were some high-profile cannabis groups of, you know, that were Distributing it and they were very vocal. Those were the ones rated by the DEA in the early days, not the ones kind of keeping to themselves. Keeping it quiet and just doing their thing. So there's always the potential for Selective enforcement. And so, you know, and like this initiative and Oregon, which is a state level legalization of psilocybin therapy, which is really interesting, you know, part of their plan for two years is to figure out how to integrate
Eight with the federal level. And I don't know how that's going to go because like unless you rewrite the Controlled Substances Act. It seems like the best you're going to get is a tolerance from the federal government. And you know, and that could be very, you know, hey you change administrations
and this is psilocybin by prescription from a medical doctor or you're talking about therapists in, who have mastered.
There's degrees or phds or self-appointed, coaches or something like that. Administering, psilocybin be, but without any oversight.
So this is all getting figured out in Oregon case. And again, there's that two-year period of like basically, we're going to figure this out. And so what is it with Oregon? Honestly, you know euthanasia. I love this state of Oregon. It's but
it's interesting how you have these Pockets. Oregon Vermont seems to be one, you know, you got these kind of pockets where people
Our experimental with plant compounds, they seem to be green woodsy areas for in, at least, in my mind, but they're, they're sort of our culture around plants and the use of plants is
Therapeutics and combine. That with the West just did more geographically of more of the the anti, you know, federalism the anti mean the Oregon ranchers from several years ago that held up the you know, the whatever Wildlife Place, you know, and that was a big Showdown with the feds, you know, and the Cuttino.
Just kind of the West is kind of known for you know, more of those issues. So he combined the to the hippie-dippie, California, Oregon by
becoming less hippy-dippy the than, although it was that there's always been a tradition not just in the culture around drugs, but certainly in Academia and in Tech etcetera that the West has been a place where people have tried to throw off traditionalism and kind of lineage.
And like who your parents are, what school you went to and and the past as a determinant of what's next and exciting about the future. Whereas, and here we are in East Coast institution, guy and West Coast institution. Got I think that it's this idea of kind of innovation and the future versus do we stay grounded in history and tradition, right? And of course, they're great institutions on both sides. What's interesting. Is that Hopkins Johns Hopkins?
Let's go. I think of as a real like East Coast academic institution. It is on the East Coast but here you are doing these very pioneering and important and exploratory studies in a certainly not a hippie dippie environment. Oh,
yeah, berrykins is not high tree Department even among Psychiatry departments. And as a psychologist and a psychiatrist varmint Psychiatry is certainly more conservative than psychology even with in academics. But even among psychiatrists
AIG departments, very conservative department. So
we got the law at the federal level. We've got the law at the state and local level. And then we've got this question of whether or not it's going to be Physicians. So, MDS people with phds or master's degrees or whether or not, it will be kind of a free for, all right, for consumption. And we catches the life coaches and, and, and the general public. I mean, right cannabis. Yeah. I'm not a pot smoker. I just, it's never appealed to me.
That's just me and my pharmacology but, you know, you can buy cannabis most places in the US without a ton of risk. It seems right. Are we going to see a time in which you can, essentially go into a shop on Abbot Kinney Boulevard in Venice, California. And, and right now, you can go buy marijuana. If you have a marijuana card and it's my understanding. I see a lot of people going in and out of these stores. The
Lise certainly have no problem with it is they're going to come a time where people can just go by psilocybin.
Do you think like a human Amsterdam and have your think that time is coming?
I think so at a certain point and I don't know how long it's hard to imagine our current level of drug criminalization holding up for and I'm thinking like, large spans of time like really in a hundred years. Are we going to be doing this five hundred years? Like how could that it's not going to be sustained sustained but in five years entrance, so I don't think so in
United States. I do think eventually you're going to see something like that because I was going to be no way and I think we're going to I hope that we're going to eventually come so strongly. We're going to move on from this model of criminalizing drugs that we're really going to focus on regulating drugs at the right level for that drug and I like the word regulation better than legalization. So, I mean I could imagine what one day regulation, smart regulation might mean for
Or psychedelics, maybe it could mean that there will be whether or not you have a diagnosis of a problem. It may be that even for personal exploration. You can do this legally, but you first have to, maybe take a court, get a drive. In this has been I'm not the first to say this begin equivalent of a driver's license. You have to go to get some sort of training. Maybe your first number of experiences need to be with, with trained guides, who can facilitate it and then the public health information for anyone using this.
That this is what riskier uses all use is going to have wrist. This is what riskier uses. This is less risky. Use. These are the factors. So I think eventually we're going to be getting for any but I would say the same thing for like methamphetamine and and you know heroin and cocaine like all of these drugs, it's hard to imagine the current approach of just feeding a black market and really exacerbating a lot of the harms from drugs, you know, you know that happens under the current model. It's hard to imagine that.
Painting that isn't to say. I think it should be in all of the 7-Elevens, you know, sold to kids at at the other. I would hope not, but I do think it's probably not going to be soon in the United States. I do want to make the major point that even if psychedelics had never been made illegal. I think the exact the trajectory of the medical research right now with still need to happen if it's effective as an antidepressant. Like we need it to be, you know, there's all the evidence.
Suggesting that whatever disorder were talking about. The efficacy is going to be increased and the risks are going to be mitigated drastically. And the types of models were talking about with the screening with the preparation with the integration of cognitive behavioral therapy or what-have-you depending on the disorder. You're treating with the integration afterwards with the professionals. So it we would be doing it anyway, so it's not like this versus that. So I don't see it as a race between the decriminalization or legalization.
Of these compounds versus their medical development. Some people who are psychedelic fans get all into a bunch about the medical development. They say you guys want to like you want to, you want to keep it only for, you know, for your medical research and I retire and you want to be in control of it as academics. And my take is, I didn't make it illegal for anyone. We're only moving the needle in One Direction. And again, even if it was already illegal, and because and I've done plenty of survey research,
People reporting, they took mushrooms for fun or for personal exploration and they said my God, why am I smoking and they quit smoking 20 years because of it or it's help with their depression or it's help with them overcoming alcoholism or these different. Sometimes that happens out of the blue. When people use psychedelics, nonetheless, obviously, the efficacy rates are going to be higher when you bring it into these medical models and it's going to be sure safer. So we are going to, you know, so we need to be pushing that and my best guess is that MDMA is going to be approved.
And within the next three years
and for prescription by a physician,
yes in. And not just, you know, take two and call me in the morning. But in the Clinic's, the way that those those PTSD trials are being run. So the MDMA would be approved for PTSD and every disorder needs to be looked at separately and it's going to only be approved for those things. Now, there's
any questions in a legalized and regulated or you know, now we're getting into the Nuance. I think when people hear it's going to be approved in two years. They think that they'll be able to buy and sell.
Use MDMA without legal consequences and I do not think that's going to be. The situation is not the way it is. And I will say that
I think the quote unquote psychedelic Community. I mean they've been doing what they want to and will carry on doing what they want to anyway, right? It's not like the little legal status has has prevented them from doing what they're doing. In fact, unlike Leary and Timothy Leary and Huxley. And and you know, and some of the others that were very vocal and lost their jobs and some of them went to jail, Etc. I mean, you got a lot of public figures now like McKenna and others are just basically out there talking about.
Psychedelics. Michael Pollan who's more of a writer? Foodie Guide Gun, psychedelic dabbler writer guy. I know, he's kind of a polymath but, you know, the league, the legal status didn't seem to hinder their at least Online Career. So I don't know. I don't know. I haven't looked at their bank accounts, but that I'm imagining they're doing just fine. Right? So, the fact that the work is happening inside of big institutions. I think it's important that you point out, and I'm just trying to underscore that.
That's that's in no way antagonistic to what people are doing. It's in support of a different sort of mission, which is to explore the validity in different contexts in a really controlled way, which I really, you know, it's I think it's really important Mission. I want to make sure that I ask you about the other really important mission that you're involved in with, respect to psychedelics, which is not about depression per se. But is about neurological a neurologic injury.
Or head injury. I realize it's early days for this but I think there's a lot of concussion out there. Sadly. There's a lot of TBI traumatic brain injury. Yeah, not just from Sports. I think people sometimes forget that it's not the major source of traumatic head injury is not football. It's not hockey. It's not boxing. It's not any of that stuff, its construction workers and its people. I mean, if you've ever seen the helmets that construction workers where, I mean, they act Hammer. Yeah, my God jackhammer.
And not be just, yeah, I have a colleague that works from this and bioengineering and when you look at the, you know, we always think sports. But there are many people who make a living in a way that is over time, is detrimental to their brain. And they don't have the option of just not being a professional wrath leader, something that sort. And if
they're not doing the construction, someone else needs someone else to do it, right? And we forget for
some reason and I to, I didn't occur to me until I heard it, like, the people who are doing construction and then of course,
Bike accidents and falls, and things like that as well.
So it's Harry
military. Absolutely. So what do you think is the potential for these compounds particular psilocybin, but other compounds as well for the treatment and possible, even reversal of neurological injuries and what sorts of things are you excited to do in that realm.
Yeah. So this is definitely on the more exploratory and so it's based upon. So, you know, this is sort of
Of beyond the Improvement of psychiatric disorders, like
depression or
depression, anxiety associated with the
terminal illness or
substance use disorder the addiction. So those are sort of psychiatric, you know, disorders. So this is, you know, these, you know, there are anecdotes of people saying that that psychedelics have helped heal.
Brain, you know, they've been in one of these situations like in sports a sport where there's repetitive head impact and they're claiming that using psychedelics has actually improved their cognitive function, for example, improve their memory including improved their their mood, but but it's kind of more of the, you know, the cognitive function things like memory are. Now caveat is if you successfully improve, someone's depression, you can get
Some cognitive improvement too, but that's a more of a weaker, more indirect effect. But if you take these anecdotes and you combine it way, across orders of analysis to the rodent research, from several Labs, like, David Olson, Brian Roth. These folks that have shown different forms of neuroplasticity unfolding after, like, sort of post acutely. So after in the days, following the administration of psychedelic compounds occur.
Now a variety of Psych about that would compounds and even some non psychedelic structural analogs that you see these different forms of neuroplasticity. So the growth of dendrites and new connections being formed with with different neurons, so that those effects may be at play and the improved in the psychiatric treatments that we're dealing with that hat. We don't know that. It seems like a decent guess and we're going to be
Figuring out whether that's the case, but another potential that that sets up is that maybe that's what's going on with with, with these claims of improvements from urine neurological issues that there's actually, you know, repair of the brain from injuries underlying, you know, things that, you know, situations where those repetitive head impact, perhaps there's a potential for for helping.
Folks recover from stroke
and disorders like that. There's a wide variety of disorders. Now that it's a bit of magic and a bit of like, it's something that the Enthusiast kind of can do some hand waving and claim that this is already known. It is more exploratory. But what I'm hoping to do is some work with retired athletes who have been exposed, but by the nature of their sport, for example, in an a athletes in the UFC who have been
Exposed to repetitive head impacts, like a lot of sports, a lot of, you know, Sports expose people to and who are retired from the sport and are suffering from say depression, which can impart result from those types of that history of head impact. See if we can fix the depression. But then also as a cherry on top in a more exploratory, aim, see if we can have evidence of
Of improvement in cognitive function and Associate like using MRI. See if it affects gray matter over time, these types of things to see if they're actually some evidence of this improved, like, this more direct repair of the brain, but it again, it is very sort of like we've got some rodent data. We've got some human
anecdotes. We will acknowledge its early days and we look forward to seeing the data. I appreciate how cautious you are.
In tentative, you are you're not drawing any conclusions. I think from a purely, logical, and somewhat mechanistic perspective. I mean if we assume that lack of ability to focus or degradation and mood is the reflection of neurons in the brain. I think we can agree on that. Some dialogue between neurons in the brain. And that what needs to be changed? Is the nature of that dialogue. AK, neuroplasticity. We know that real
During of neural circuitry require in the adult requires these things like intense Focus followed by rest etcetera, but the basis for that like beneath focus is the mechanism is a mechanism rather beneath. The the bin that we call deep rest is a mechanism and those mechanisms are neuromodulator driven. So to me, you're I'm not reviewing your Grant but but from a rational perspective, it seems that drugs that increase
certain neuromodulators like serotonin or dopamine in a, in a controlled way. And then coupling that with learning of some sort sensory, input of some sort. It makes sense that, that would lead to could, I should say lead to reordering of circuitry that would allow for better thinking better mood, many of the same things that you've observed in the clinical trials for for depression. So the rationale is really strong. I think that's a very exciting area.
You know, I get asked all the time about TBI and traumatic brain injury and right now, you know, it's kind of there isn't a whole lot that people can do and people are dabbling in the space of, you know, hyperbaric chambers and people will do sauna and breathwork and you know, and people are kind of, you know clipping at the margins of what really is a problem that resides deep to the skull. So I think I just want to applaud that the exploration. I think it's great provided that exploration is being done in a controlled way. It sounds like that.
What you're doing with the UFC? Yeah, it's
that we, they were really gracious and had myself and a few of my colleagues out to their headquarters in Vegas, impressive place. Right? And it's in process, you know, there's a dialogue going on there. I'm hopeful that there's going to be some some work with them, but it's in process now in terms of exploring that there's a real interest and I'm I'm just really impressed by the organization and their commitment to athlete health and
I am we'll see.
Yeah, I am too. We have a colleague out there. We're doing a little bit of work with them. Duncan French, who's a serious academic in his own, right? And I think when people hear UFC, they just think about the octagon and fighting and, you know, Pay-Per-View fights and things. But in talking with them and I'm sure you've had these discussions as well. They are very much interested in the Health and Longevity of their Fighters. They are also interested in the Health and Longevity of their Fighters being a template for how to treat traumatic, brain injury and improve human.
Performance in other sports and in the general public. And I think it's not an image of the UFC that is commonly comes to mind because they haven't been, you know, particularly verbal about it in the Press, but I think it's great. They're bringing in academics. I mean Geeks like us going to the out to the UFC performance center. I mean you do MMA, but I'm basically just a geek walking through the place, but the fact that they're interested in talking to scientists is really, I'm biased here. But a point in their favor along the lines of other
Groups and individuals that have impacted the space that you're working in and this pioneering of the Psychedelic space, you know, a few years ago. I think, if someone submitted a grant saying, I want to study how psilocybin impacts human depression, I'm guessing having worked on these panels before that. The response might have been closer to. Well, we need to do a lot of studies in rodents and a lot of studies in primates, and then maybe just maybe we could explore.
These drugs, because the National Institutes of Health actually has a whole Institute devoted to addiction, right of exploring compounds, only in terms of their negative effects, right, which is a very,
which is where I've gotten all of my NIH funding, which is so interesting, right? And it's a
super important Institute. I want to be clear. They're amazing people there, but philanthropy and Foundation have been very important in supporting pioneering research. And so maybe we just talk a little bit about
Out that so your lab receives funding from taxpayer dollars through the National Institutes of Health is that mainly where you're sort of your funding comes
from. So our group has gotten some funding from like say the National Institute on drug abuse
Nida for some a
small subset of the Psychedelic work, but only for some work, geared towards understanding these things, as drugs of abuse. Course, when you do a study though, you show us how they really explore. How
Oh, they're bad. Right? But when you doing that, you can explore like, you know, the good stuff too, you know, but but the the large majority of the work and the most interesting work has been funded by philanthropy Private Client. No, I still have some great support from Nida outside of psychedelics. I'm shifting more and more of my my time towards focusing only on psychedelics and in fact us getting the the
Enter level funding from some really, you know, big picture philanthropist like helped me to start to make that transition but groups like to have to research organization, Dennis McKenna of which is one of the founding members the brother Terrence McKenna, who is by the way, an ethnobotanist. That's what is, what does that do? Use after studying the, the essentially, the anthropology of psychoactive plant
use, so you can get a degree in that.
Yeah. Yeah, you know, hanging out.
Hang out with cultures and studying their use of these compounds in the traditional
ways at Hopkins. There's it, that degree exists at John's.
I don't, I don't think that degree exist at Hopkins. But I mean, the kind of the most, you know, as you'll as, you know, from Academia, I'm not, you know, sometimes folks. I'm not sure how many people's phe is actually in ethnobotany or something else. But the real focus is like my degree is General experimental
psychology, but I wasn't kids out.
I just decided they're going to major in ethnobotany. But you know,
the mean, one of the pioneers of the Psychedelic area before Leary and before and actually he was late, even for the human researchers, like folks, like, humphry Osmond and Abram Hoffer and Sydney Cohen were earlier. But even before those folks, Richard schulte's at Harvard, he was, I mentioned him earlier in the conversation, discovered, all of this, that these various tribes using Ayahuasca, or yog, a different name for the same thing throughout South America.
These DMT containing snuffs and all of this. So, you know that was, you know, ethnobotany this kind of this kind of intersection of anthropology and these psychoactive plant compounds. So the have to research institute which Dennis is a, is a founding an active member of a board member. They have funded a lot of our early work. There's also an organization called the Beckley Institute.
Based in England, that a lady Amanda Fielding is that has been the head of that has they provide at the first funding for our psilocybin smoking? Cessation, research and Hafner came in and provide its subsequent funding. But it's and then there are other groups that counsel and spiritual practices a great guy and named Bob Jesse funded some of the original work at Hopkins. Looking at the nature of mystical experience outside of treating disease, States or disorders, but just
Adding these, like, like people take these compounds and astonishingly, you know, frequently will say. That was the most important everything I've ever experienced. It's like, what the hell is that? Yeah. I did
someone mention recently. I think this might surprise people little bits, but certainly surprised me. I had a friend who adores his children. He's got three children, adores his children, happy marriage, and great, great father. They're both great parents, and he told me that as part of a clinical trial here.
Had a DMT experience that he claims. He said I'd love to tell you that it that the birth of my children was as profound. But if that was a more profound experience and the birth of my children, any one of them and all of them combined and I was like, wow, I've never done DMT by was like wow, that's a pretty strong statement. Now, he did it in the context of one of these, you know, clinical Explorations. I assume that was part of a legal clinical trial, but the I mean, that's saying something it's saying something and he's a very rational, very,
Good guy otherwise, but so philanthropy foundations and then in
as recently as I just affect you because I can't skip it our Center where you can get paid. That's like we I mean the Hefner group, The Beckley group. I mean, these are wonderful. I mean, these are people that have been holding the flame alive during The Darkest Hours like the rain. Same thing with MD with the maps organization on more on the MDMA side, like holding that candle during the darkest years.
That you know, so we've but you know smaller organizations connected to smaller but growing over time, you know, pockets of wealth, but you know, we basically limped on limped Along on a wing and a prayer until recently when we got the 17 million dollar gift so that we could create a nominal Center. And as you know, basically to the university that means you get a certain number of dollars and a lot of them, you can call yourself a center, you know, it's a capital investment, you know staff, you know equipment.
Salary support, which is the always been the huge thing for us, but the 70 million Gala get gift, which was split between the the, the Cohen foundation. So Steven and Alexandra Cohen, and they covered half of it and the other half of the Tim Ferriss, collaborative. Basically Tim and a few friends ponied up that the, you know, divided the rest of that half of that 17 million dollar gift and came together to just, I mean, it just it's completely.
And our, the work that we've done in our ability to, like to fully delve into this area. And not worry that like, oh, if I focus on this rather than putting another three night of grandson, some other topic that may or may not get funded. Like, if I focus too much on the psychedelics, am I putting my career at Jeopardy? But like, so,
you're knowing, not only a tenured professor, you're also full endowed rights, and that
came. By the way, when you say, somebody is a fully endowed
Professor or be very clear what that
It means that means that there's
minding all of the above, but now I have no knowledge of your particular situation,
but you probably do. But sure the and these what we're essentially saying is that funding which does not change somebody's salary level. I just want to be clear because I think the general public is in. There's no reason why they would understand all the nuts and bolts of how this work getting these weird. Yeah. Academia is weird because it we're not talking about increasing.
We're not talking about an endowment that were philanthropy that went to increase Matt's salary. That's something that's set at the University level. It's always been said and it is at least is still true now, which is that, you know, nobody goes into science for the money at least not at the academic level not at in Academia, but allows people to devote more of their time and energy to these exploratory Realms like
Like psychedelic research or the case of my lab, the work that we're doing with David Spiegel is lab on, on respiration, breath work and hypnosis for modulating brain States. These are not typically areas that the National Institutes of Health and other major organizations have institutions set up to support. Now. There is an exciting initiative, which is the ncci H, which is complementary Health,
right to be in cam. Yeah. Yeah, at NIH. And now we're not just
throwing out acronyms just to, you know, to bat back and
Acronyms, but I think what we're looking what we're seeing now is a movement toward Science, And scientists and clinicians and the general public and philanthropy being engaged in this dialogue, which says, okay, there are problems in the world, depression, head trauma, psychological trauma, PTSD ADHD, these problems. Clearly exists. The solutions are going to involve behaviors that are going
Involve nutrition supplementation, social connection. However, there are drugs. There are compounds that can change the brain and allow the brain to change its circuitry through experience and psychedelics are one of several others, but one of the you know, powerful levers it sounds like and and I just want to say, I think the reason I reach out to you and so excited to sit down and chat with you is because
I see very few people inside the halls of Academia who have thrown their arms around this issue of psychedelics in a way and gone through the trouble of trying to find the funding to get it done gone through the trouble of trying to set up clinical trials. I know what's involved in doing this. It's so complicated. So time-consuming and painstaking and you've made real progress. I mean, you guys are publishing papers. There's a new dialog emerging that isn't just books on bookshelves and
Um and you know, psychedelic psychonaut gurus on the internet who also play an important role, but you're really moving this field forward. And I know there are others as well their colleagues in England and others as well. We will acknowledge them, but I just want to say personally that I'm like inspired and impressed. By the way that you've gone about this and the level of rigor. I mean, when I ask you a question about serotonin, most people just kind of kick back to me. Well, yeah. You got receptors in.
You got to legging, but I mean, it's clear to me that you care about the details and that you care about the future of this area. And you also really care about these patients and these individuals. So I know I'm speaking on behalf of a ton of people now and in the future, they don't even know what they're going to receive as a consequence of this. I just want to voice a real sincere. Thank you for that effort. It's like your lab and your work matters and that's
That really special and unique
that I appreciate that and I had a good colleague. In fact, shared some Grant support under the multi Pi system years ago, and she actually took a job at in at, at NIH as a review officer. And I remember her telling me, you know, and she actually left when she had multiple ro1. So it's like, she didn't
know you are ones are kind of that the potato butter, a big, big grants that every every card-carrying, it's a mark of respect in our
Merely to have a one or several of
these. Yeah. Yeah. Yeah. Yeah, I mean, you know, and it's like you eat what you kill and Academia gets to what we're talking about later. It's like you don't make more money by pulling more grants, but you're able to pay the salary that like the university doesn't pay you your salary. Your it goes through them. You're just able to do more work. Yeah, and you're able to like and if you don't pull in the grants to cover your salary, your job and come to an end, even if your tenured at a place like Hopkins, they can do tricks like slowly.
Our your salary over the so you're just let you know, just for you anymore.
They just take away your space.
Yeah, they put you in a closet and give you no support for trainees and basically make life hell for you. So, you know, drive a cab and Baltimore and call yourself a full professor at Hopkins truthfully, but you may not have no ability to sure they're out there done. But, um, but yeah, I remember one of the things this colleague has said who is successful but left on top said, I really don't know that I'm making a difference in the world and she did some great memory research.
And and connected to drugs, also connected to aging. But she she said, I don't, you know, I don't I don't feel the impact of what I'm doing in the real world and it's you know, unfortunately there for a lot of academe what we do it stays in the Ivory Tower, you know, the world is a, you know, not its place and like a lot of this doesn't disseminate and and because of the various structures the way the world is set up and thankfully this I mean because the work that
that that our group as well as a few others around the world over the last 20 years. It's like you do have an emerging, psychedelic startup industry now with billions of dollars of investment. And yeah that's going to turn into both good and bad. Like, you know, it's upping the ante like there's going to be a lot of good and bad that comes from that but any new technology is going to result in that. But we got psilocybin designated for two separate entities as a breakthrough therapy by the FDA and people may not realize and MDMA
Is designated as a breakthrough therapy for M for PTSD? This is a really big deal. That's a very high. I mean, Pharma companies would pay millions of dollars to get their new drug, a designation like that, and what it means is, it shows early research has shown saying, it shows a high potential for treating disorders, that don't have very good treatments. So we're and we're probably again a few years away from both MDMA in, probably a year or two after that psilocybin being treated.
Added for PTSD and depression respectively. This is you know, we have to wait for the phase 3 studies. But if the results hold up any even if the effect size is like have what we're seeing now, it's still going to be a lot larger than what you're seeing with the traditional medication. And so it's going to be approved if the data hold up and it probably will for my judgment. So, I feel like, what I'm doing is actually having a positive impact in the world in a way that and I feel I feel lucky that I
At interested in area that happens to plug into a place in the world. Where there is that opportunity where some great colleagues and friends are focused on areas where.
I wish they had the opportunity for their work to be disseminated. I wish that I mean I was lucky to be interviewed on 60 Minutes because of this work and I was like, oh my God, I know so me. There's a bit of you know imposter syndrome like, oh my God. I know so many scientists that deserve, you know more so than me to be had that level of exposure. But if you happen to be in that place where it's
You got to do your best to make it work to take advantage of that luck and that intersection of the world and to push it. And you know, I've been lucky but also did take a bit of a leap of faith early on. I did have some, you know, advisors, that told me like you got a really promising pedigree early on. Like, are you sure you want to focus on
your Island? The Psychedelic stuff? You've been, you've embraced risk. I mean, I think that I mean the world's changed since in 2020 certainly but you know, channels like social media.
Your podcasts and things of that sort, you know, your exposure is because people are interested in these topics and that's why people like myself or are interested in talking to you. I mean, you know, at Stanford there are now a few Labs starting to explore psychedelics more at the mechanistic level. But so an animal models, excellent Labs, but also I can imagine because of the pioneering work that you've done and Hopkins, it'll start to become more common. I'm certain that people.
You are going to have questions about how to get in contact with you and learn more. If people have trauma, PTSD, depression, you know, you, it's likely that they're going to start seeking ways in which they can potentially participate in clinical trials. You're very active on Twitter active. I should say, you've got other obligations but where you are active on social media. You're active on Twitter. It's drug. It's at drug down score
researcher. Right? Right, right, okay.
Drug underscore researcher, that's how to find me, great account, by the way, Matthew and I recently got into a dialogue there about some of the deeper effects of psychedelics and literature versus how they're being discussed in the general public and I follow his account. It's a really wonderful account for whether or not you have a science background or not. If people are interested and I'm going to try and persuade you to be more active on Instagram, but I don't know if I'll succeed in that had to get my into your busy guy and I guess
At it, I'm running a lab to I get it, you're busy. But but we drugged down score researcher there as well. The same handle your lab at Hopkins is pretty straightforward to find through a Google search of your name. Matthew Johnson. Johns, Hopkins University. Are there portals for people to to explore clinical trials, participation in clinical trials of
various? Yeah, and so in our group so you go to Hopkins psychedelic dot-org. That's the website and
We can't remember that just Johns Hopkins psychedelic. Yeah, we have and you're going to find us. It'll be the first thing that pops up and we have trust me. If we have a study on something. It's going to be on that website.
That means he's very being very polite. So I will be a little bit more aggressive and say don't email him directly. He won't see that email wait until there's a posting for a study and then sign up through the correct
portal and I tried to get back to those emails, but frankly and it's a it's cuz you know, I'm
Lucky, the area has taken off so much, but there are many days where I simply get so many to do. Reverse arrest that I have to do the research my day. Yeah if I answer all the so so yeah, trust me if there and something that a lot of folks don't get and being in Academia. Like we are it's easy to forget how people don't understand. We don't realize this, this is experimental research. It's FDA approved as an experiment, you know, so we're working towards formal FDA approval for straight-up clinical use, but right now someone can't bring me a case of
Some idiosyncratic thing and and say I'm suffering from this complex constellation not a clinician and yeah, I'm not a client and even if I was I wouldn't be able to treat them with psilocybin or to send them anywhere that was legal to to to take it, you know, so if we're going to be treating you it's it has to be or anyone else in the United States or most other countries for that matter. It's going to have to be under the guise of a very specific.
Protocol this number of milligrams to treat PTSD to treat major depressive disorder to treat, you know, treatment-resistant tobacco, use disorders of nicotine addiction very specific studies. This is not one off treatment and folks say like, oh I can pay to go out to Baltimore. If you see my oh my son has this, you know, complex like it in their tragic cases. But yeah, so if you're interested in a study, go to our website. If it's not on their
Side, you know, we don't have a study on it. There are going to be forthcoming City. So I'm going to be starting studies on opioid addiction and PTSD and an LSD study for chronic pain. It the day that those are open for recruitment. They're going to be up on our website. So that's where you look to see everything. And in fact, I would just recently couple days ago, put up a couple surveys. Also where we post links to our survey study. So if you, if you had psychedelics and you've taken them for therapeutic intent intent for PTSD or depression, or
Anxiety. You can find a link. And also if you've done breath work, for those reasons, we have a link for a study of that type up there now, which is a holotropic style, Brett, very psychedelic type of of a breathing technique that can lead to some of these similar experiences. So it's up there more broadly outside of our group because there's a growing number of groups in the u.s. Doing this re and in Europe doing this research, but you can go to clinicaltrials.gov and if you lookin for the
The main search term of psilocybin or MDMA or psychedelic plug in those terms. You can get a list of the growing number. I mean, I think there's I think there's over 40. Maybe it's been a while, there might be over 50 now. I don't know but studies with just psilocybin going on right now in clinical trials.gov. So check out clinicaltrials.gov to see what's going on, but it's going to be if you're going to do anything legal. It's going to be in the context of a very specific study. It's not going to be one.
Knopf treatment,
right? Yeah, I should say just and not just legal, but also supported in the right framework, that you described of having a team Etc. Obviously, people will do what they will do and seeing if
yeah, I wasn't if people, I never encourage people to take drugs of any, I don't encourage caffeine use every drug has its risk, I encourage my own caffeine. I am. But yeah, else's, I'm
drinking up right now. This is great. Yeah, this is very strong mate. It's what we're
Making it does not lead to a alteration. In my perception of self to the extent that we talked about earlier. However, this conversation wasn't a good example of how we can enter a perceptual bubble. I learned so much about psychedelics and the future of this, for sake of mental health and other aspects of Health. Matt. Thank you so much for your time, for your knowledge. And I think you put it best earlier for holding the candle in a very dark.
Time and then now there's light. Thank you. Well,
thanks for helping to spread that light. I really appreciate what you've been
doing. This
is a great great medium that you have going on. So thank you for doing
it. It's my pleasure. Thank you. Thank you for joining me for my conversation with dr. Matthew Johnson. If you're enjoying this podcast and learning from it, please subscribe to our YouTube channel. In addition. You can leave comments and suggestions for future podcast topics and guess in the comments.
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