Guest Episode
September 19, 2021

Dr. Matthew Johnson: Psychedelic Medicine

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In this episode, Dr. Huberman discusses medical research on psychedelic compounds with Dr. Matthew Johnson, Professor of Psychiatry and Behavioral Sciences at Johns Hopkins School of Medicine. They discuss the biology and medical clinical-trial uses of psilocybin, MDMA, ayahuasca, DMT, and LSD. Dr. Johnson teaches us what the clinical trials in his lab reveal about the potential these compounds hold for the treatment of depression, addiction, trauma, eating disorders, ADHD, and other disorders of the mind. Dr. Johnson describes a typical psychedelic experiment in his laboratory, start to finish, including the conditions for optimal clinical outcomes. And he explains some of the potential hazards and common misconceptions and pitfalls related to psychedelic medicine. Dr. Johnson explains flashbacks, the heightened risks of certain people and age groups using psychedelics, and the evolving legal and pharmaceutical industry landscape surrounding psychedelics. Dr. Johnson also describes how the scientific study of psychedelics is likely to set the trajectory of psychiatric medicine in the years to come. Dr. Johnson is among a small handful of researchers who have pioneered the clinical study of these powerful compounds. He has unprecedented insight into how they can be woven into other psychiatric treatments, changing one’s sense of self and reality.

Links

  • 00:00:00 Introducing Dr. Matthew Johnson
  • 00:02:10 Supporting Sponsors
  • 00:06:40 ‘Psychedelics’ Defined
  • 00:14:09 Hallucinations, Synesthesia, Altered Space-Time Perception
  • 00:19:56 Serotonin & Dopamine
  • 00:23:50 Ketamine & Glutamate
  • 00:28:00 An Example Psychedelic Experiment
  • 00:37:30 ‘Letting Go’ with Psychedelics
  • 00:44:10 Our Mind’s Eye
  • 00:48:00 Redefining Your Sense of Self
  • 00:58:56 Exporting Psychedelic Learnings to Daily Life
  • 01:04:36 Flashbacks
  • 01:12:10 Ayahuasca, & ASMR, Kundalini Breathing
  • 01:15:54 MDMA, DMT
  • 01:26:00 Dangers of Psychedelics, Bad Trips, Long-Lasting Psychosis
  • 01:38:15 Micro-Dosing
  • 01:56:45 Risks for Kids, Adolescents & Teenagers; Future Clinical Trials
  • 02:03:40 Legal Status: Decriminalization vs. Legalization vs. Regulation
  • 02:18:35 Psychedelics for Treating Concussion & Traumatic Brain Injury
  • 02:27:45 Shifting Trends in Psychedelic Research, Academic Culture
  • 02:44:23 Participating in a Clinical Trial, Online Survey Studies, Breathwork
  • 02:50:38 Conclusions, Subscribing & Supporting the HLP, Supplements

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Andrew Huberman:

Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.

Andrew Huberman:

I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology 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 Psychedelics and Consciousness Research. As many of you know, there's extreme excitement about 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 changed, such that people can combat diseases like depression or trauma or other disorders of the mind that cause tremendous suffering. Dr. Johnson is also an expert in understanding how different types of drugs impact different types of human behaviors, such as sexual behavior, risk-taking and crime.

Andrew Huberman:

Dr. Johnson and his work have also been featured prominently in the popular press, such as articles in The New York Times, in 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 talk about psychedelics at the level of what's called microdosing, whether or not it is useful for the treatment of any mental disorders.

Andrew Huberman:

We also talk about more typical macro dosing, what those macrodoses 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 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.

Andrew Huberman:

It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast, and now my conversation with Dr. Matthew Johnson.

Andrew Huberman:

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. So-

Matthew Johnson:

Likewise. Big fan, and happy to do this with you.

Andrew Huberman:

All right, well, thank you. My first question is a very basic one, which is, What is a psychedelic? We hear this term all the time, but what qualifies a substance as a psychedelic?

Matthew Johnson:

Nomenclature is a real challenge in this area of psychedelics. So starting with the word "psychedelic," if you're a pharmacologist, it's not very satisfying, because that term really spans different pharmacological classes. In other words, if you're really concerned about receptor effects and the basic effects of a compound, it spans several classes of compounds. But overall ... it's really more of a cultural term, or it does have a relationship to drug effects, but it's 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 it is, they all had the ability to profoundly alter one's sense of reality, 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, what are called the classic psychedelics.

Matthew Johnson:

So in the literature, you'll see that term. Hallucinogen and psychedelic all have traditionally been used synonymously. I think there was a little of a tendency to stay away from psychedelics because of the baggage, but there's been a return to that in the last several years. But the classic psychedelics, or 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 peyote cacti and some other cacti, like San Pedro. And even amongst these classic psychedelics, there are two structural, structural classes. So that's the chemistry. There [are] the tryptamine-based compounds like psilocybin and DMT, and then there's the phenethylamine-based compounds. So these are the basic two building blocks that you're starting from, either a tryptamine structure or a phenethylamine structure.

Matthew Johnson:

But that's just the chemistry. 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 to the behavioral and subjective effects. So all of these classic psychedelics serve as agonist, or partial agonist, at the serotonin 2A receptor, so a subtype of serotonin receptor. Then you have these other classes of compounds that you could call psychedelic. Another big one would be the NMDA antagonist. So this would include ketamine, PCP and dextromethorphan, something I've done some research with which folks might recognize from like robotripping, guzzling cough syrup, which is something high-school kids are known to do when they can't get ahold of real drugs, that type of thing. So a large overlap in the types of subjective effects that you get from those compounds compared to the 2A agonist classic psychedelics.

Matthew Johnson:

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, salvinorin A, which is a kappa-opioid agonist, which again-

Andrew Huberman:

Where does that come from?

Matthew Johnson:

Salvia divinorum, it's a plant that became ... 20 years ago, it popped onto the 'legal high" scene, and there's a long history of this predating the Internet, going back to the stuff one could order in the back of High Times Magazine, and most of this stuff never worked. Or it's like, just smoke enough of anything, maybe you get a little bit lightheaded. But this is one of those things that popped around 20 years ago, when it quickly got the reputation of 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 psychedelic. And we did the first blinded controlled human research with salvinorin 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, I probably should have mentioned even before the salvinorin A, but you have MDMA, which really stands in a class by itself. So it's been called an entactogen, and-

Andrew Huberman:

What does that mean?

Matthew Johnson:

It means touching within. It alludes to the idea that it can really put someone in touch with their emotions. It's also been called an empathogen, meaning it can afford empathy. But I think entactogen's probably, that's the term that I tend to focus on. I know I'm not telling you anything you don't know, but for the viewers, the primary mechanism of MDMA is serotonin release, and to a degree, other monoamine release: dopamine, serotonin.

Matthew Johnson:

And so structurally, that's also in the phenethylamine class, which contains mescaline, the classic psychedelic, but also amphetamine. So just like Adderall is in that phenethylamine class. And so this is another example where chemistry doesn't dictate. I mean, you can tweak a molecule, it might have that same basic structure, but now you've profoundly changed the way it interacts with the receptor. So in MDMA, it does not exert its actions by, I like to say, by mimicking the baseball entering the glove, the postsynaptic receptor side, acting as an agonist. So mimicking the endogenous neurotransmitter serotonin, like the classic psychedelics do. MDMA works on the pitcher side of just basically throwing out more of the natural, the endogenous-

Andrew Huberman:

Dumping more serotonin.

Matthew Johnson:

... dumping, more serotonin, flooding the synapse.

Andrew Huberman:

So I get the impression that the psychedelic space is an enormous cloud of partially overlapping compounds, 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 sense that you can hear colors and see sounds, for instance. A common report of people that take psychedelics in sufficiently high doses. So hallucinating, synesthesia.

Andrew Huberman:

And then in terms of sense of self, 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. 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 your speed, and all that kind of stuff, right?

Matthew Johnson:

Yeah.

Andrew Huberman:

That gets more complicated 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 the blending of senses; is it fair to say that?

Matthew Johnson:

I think it's fair to explore that area. Here's what I'm thinking. Clearly, there is a changed relationship, certainly at the right dose, of orientation in space-time. I'm primarily a behaviorist, and in terms of human behavioral pharmacology, and I always go to comparative pharmacology. What can we say that is truly unique about the classic psychedelic, or psychedelics in general. So with that description, I'm thinking, okay, alcohol can really screw up your time-space orientation.

Andrew Huberman:

And the proprioception, your balance, your vestibular.

Matthew Johnson:

Proprioception. And in many ways, and in those gross motorways, like far worse, of course everything's dose-dependent, but in the classic psychedelics, obviously, the benzodiazepines being very similar to alcohol, same thing. So I'd want to 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, the idea that that's a mediator, that there's fundamental about changing the representation in time and in space; there might be something to that. I think of these as, psychedelics, as profoundly altering models. We're prediction machines, and so much of that is top-down, and psychedelics have a good way of, loosely speaking, dissolving those models. One of the, the reality-

Andrew Huberman:

Can you give us an example of one of, like a model? I know that when I throw a ball in the air, it falls down, not up. 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.

Matthew Johnson:

And with a four-year-old, I mean, I saw that at earlier ages, like that experimentation of "Oh yeah, that's what happens."

Andrew Huberman:

So if a 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 too.

Matthew Johnson:

It'd be a pretty psychedelic experience, probably.

Andrew Huberman:

Right. And so there's a rule there. You're saying there's a prediction. There's a rule that underlies a prediction, that when that rule is violated, all of a sudden the circuit, presumably, for that prediction would go ... it doesn't have a mind of its own. It's somehow it creates a surprise element or a recognition element.

Matthew Johnson:

Yeah. It's not filtered out. This might sound extreme, but there are these cases, it was overblown in the propaganda of 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 jump out of a window. Now, far more people every year fall. I mean, who knows-

Andrew Huberman:

Sure.

Matthew Johnson:

They fall and die out of, from height because they're drunk. So this is extremely rare, but there are some pretty convincing cases. There was one research volunteer in our studies that, she looked like she was — in one of our studies, 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 who knows? You know what I mean. So she was into the other dimension.

Andrew Huberman:

Yeah, so they're violating these predictions. Yeah, the reason I asked 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 haven't done them before, who 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 that, as you already know, that there are many neuromodulator systems in the body, and the opioid systems, cannabinoid systems. But there's something so profound about the serotonin system and the dopamine system, because the way I define a neuromodulator is, it's a modulator, it changes the way that other circuits behave, and essentially, it increases the probability that certain circuits will be active and decreases the probability that other circuits will be active, in a general sense.

Andrew Huberman:

So compounds like LSD, like lysergic acid diethylamide, and psilocybin, my understanding is that they primarily target this 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 we're calling model challenges, challenging pre-existing models and predictions? 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. What do we think is going on in a general sense?

Matthew Johnson:

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 postreceptor signaling pathways. In other words, just fitting into the receptor. Clearly, serotonin itself is not psychedelic, or else we'd be tripping, all of us all the time.

Andrew Huberman:

Because when I eat a bagel, I get serotonin release. I mean, there's ... or turkey, the tryptophan ...

Matthew Johnson:

[inaudible 00:17:32]`

Andrew Huberman:

My understanding of serotonin is that in very broad strokes, that it generally leads to a state of being fairly ...

Andrew Huberman:

It 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. Is that fair to say?

Matthew Johnson:

Yeah. The need to do something. I mean, that's consistent with my understanding. And I'll, certainly not in terms of ... I don't primarily identify as a neuroscientist. So I definitely tell the viewers that we're far more in your domain here than mine. But in terms of how psychedelics and other drugs interface at the neuroscience level.

Andrew Huberman:

Well, feel free to explain it at the experiential level. I mean it doesn't have ... I think there probably are some audience members that are interested in, is it the 5-H2C, is it the layer 5 neurons and cortex? That conversation we could hold, and that's an interesting conversation. But just in terms of the experience of serotonergic versus dopaminergic drugs, they do seem to create distinct classes of experience. So I think that's the appropriate level for us to discuss them.

Matthew Johnson:

And in terms of how they ... I'd like to explore the biology a little bit here and tell you what's known, and what some of the ideas are.

Andrew Huberman:

Please.

Matthew Johnson:

You have this path, as you know, these are levels of analysis, and it's not which one is going on. It's almost, like, for the particular question, which level of analysis is most appropriate, is it a question best addressed by the biology, the chemistry, or the physics? That's how I think of receptor-level postreceptor signaling downstream effects on other neurotransmitters, and then activation-level effects, and then coordination of activation. So you've got, clearly with the classic psychedelics, the 2A activation. We do know that there are downstream effects in terms of increasing glutamate transmission. So this is likely a commonality, why ketamine is very psychedelic in a slightly different way, but ...

Andrew Huberman:

Do people hallucinate on ketamine?

Matthew Johnson:

Yes. It's more dissociative. So someone is more likely to be less behaviorally active. If they have a really high dose, they go into a K-Hole. If they go in a really high dose, you get in [inaudible 00:19:56] K-Hole.

Andrew Huberman:

That's called a K-hole

Matthew Johnson:

... unconscious.

Andrew Huberman:

Not an A-Hole, but a K-Hole.

Matthew Johnson:

A K-Hole. Yeah. That is very different. The K-Hole, and ketamine's interesting because people can take bumps and dance on it with the, sort of an alcohol-level strength of an effect, the classic kind of raving use of it. But then those folks want to titrate their dose because if they do more of a like a line, you get up to 75, 100 milligrams. Then you're talking about ... 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 the K-hole ...

Andrew Huberman:

Why would somebody want to take a dissociative anesthetic? To me, it's completely mysterious as to why someone will want to dissociate from their body.

Matthew Johnson:

People claim that these NMDA antagonist psychedelics are extremely insightful in a very similar way to the experiences with the classic psychedelics.

Andrew Huberman:

Ketamine is now legal for therapeutic use.

Matthew Johnson:

Right. Spravato, the intranasal form marketed by Janssen, which is esketamine, one of the-

Andrew Huberman:

It's a prescription.

Matthew Johnson:

Yeah, it's a prescription.

Andrew Huberman:

So people are taking in the nasal spray, and then are they undergoing talk therapy while they're doing it?

Matthew Johnson:

Typically not. So this is 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 discuss that experience. With Sprovato, the model is-

Andrew Huberman:

Sprovato is.

Matthew Johnson:

... is esketamine. It's the spray form of ketamine. It's been FDA-approved for treatment-resistant depression. But 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 chemotherapeutic effect, in a sense. It's not facilitating a learning process. Now there's older work. There was a guy, Krupitsky, in Russia that did extensive work with higher doses of ketamine; I should say Sprovato at the prescribed doses isn't very ... 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, in 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 going to have this experience, we're hoping you learn something from it. We're going to help you through it. We're going to discuss it afterwards. They found incredibly high rates of success, and some pretty well-controlled trials for both heroin addiction and alcohol addiction.

Matthew Johnson:

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 aren't treating it like psychedelic therapy. There's, essentially, no research at this point on that. Do you get better results? Straight up use of Sprovato. There's some good variability, but its antidepressant effects last about a week. But they kick in immediately. Now a week is a long time for most psychiatric drugs, you take it every day. So that's amazing. But it's still just a week. We're seeing effects, a year, or more later, with psilocybin and some of the classic psychedelics. 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 some work ...

Andrew Huberman:

What would that look like?

Matthew Johnson:

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 therapists in the room [inaudible 00:23:57]

Andrew Huberman:

Yeah, maybe you could walk us through this. So, let's say I were to come to one of your clinical trials, because these are clinical trials, at your lab at Hopkins, and would I need to be depressed, or could I just be somebody who wanted to explore psychedelics?

Matthew Johnson:

We've had studies for all of these, and a number of other disorders. So healthy, "normal studies," that's the code for not a problem to fix, but we're all here ... That's what amazing about psychedelics though, because 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 human, and the issues seem to come to the surface. But we've done work with smoking cessation, so people trying to quit tobacco, and haven't been successful.

Andrew Huberman:

So variety of reasons. So maybe I'll just ask some very simple questions that would 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'd show up, you said I would do several hours in advance of getting to know the team that would be present during this psychedelic journey.

Matthew Johnson:

First there's screening. So it's like a couple of days of both psychiatric, like structured psychiatric interviews about your past and symptoms across the DSM, the psychiatric bible, to see if you might have various disorders that could disqualify you. The main ones being the psychotic disorders, schizophrenia, and we're also including bipolar. So the manic side of bipolar. Also cardiovascular screening heart disease. After that screening, then the preparation where 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 explained about what the psychedelic could be like. That's a laundry list because they're more known by their variability than ... It's not like cocaine: You're going to feel stimulated, you're going to feel like you know can do any ... Or alcohol: You're probably going to feel more relaxed. I call them uppers, downers, and all-rounders, and the psychedelics are all around us. It's like, Yeah, you could have the most beautiful experience of your life or the most terrifying experience of your life. So it's just kind of laundry list of the things that could happen, so there's no surprises.

Andrew Huberman:

I think it's so important for people to hear because all-rounders, you really can't predict how somebody is going to react internally.

Andrew Huberman:

I 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, et cetera, is still very mysterious. But then I recall to mind that how most prescription antidepressants work is also very mysterious. They increase serotonin or dopamine or epinephrine, et cetera. But why they take weeks on in, several weeks to kick in, et cetera, is also mysterious. But going back to the experience of coming to your laboratory, okay, so let's say that somebody passes all the prerequisites, and it's the day, it 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 what sorts of doses are you prescribing? Is there a dose-response curve? And then secondary to that, I'd like to talk about microdose versus macrodose. So how do people receive it and how do they get it into their body?

Matthew Johnson:

So they receive pure psilocybin. So the mushroom and there are many species, the most ... People have taken mushrooms in the United States, most likely Psilocybe cubensis, they're easy to grow, they grow in cow paddies. It's easy for anybody to grow them in their closet. It doesn't take a 1000-watt, light like cannabis. It takes a little 10-watt light bulb and a Tupperware bin. So those are the types of mushrooms that people typically take. We're not administering those. Psilocybin is the compound. You could draw a molecule, psilocybin, again, based on the tryptamine structure. That's a single molecular entity. So it's a white powder.

Andrew Huberman:

Does it look like serotonin molecularly?

Matthew Johnson:

Yes, yes, yes. [inaudible 00:28:19]

Andrew Huberman:

So if I were to show people the chemical structure of serotonin, the chemical structure of psilocybin, it would look quite similar.

Matthew Johnson:

Right, right.

Andrew Huberman:

So they're basically taking serotonin,

Matthew Johnson:

A modified version of serotonin, which makes sense. But then, again, this repeated theme of the chemistry doesn't always neatly line up, because mescaline, it looks more like dopamine than it does serotonin, but yet at the receptor activation level, the pharmacological effect, those are similar, but, yeah, 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.

Andrew Huberman:

So for people that don't necessarily understand the relationship between what we call ligand, the thing that parks in the receptor, and the receptor is the parking spot. One of the reasons that you can get such a variety of effects from different compounds is, for instance, serotonin might affect a certain pathway at a particular rate, and psilocybin might trigger activation of different components of that pathway, different rates since you can get vastly different experiences 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. That what you see on paper and what you can mix up in a vial is often vastly different than what you predict.

Matthew Johnson:

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 four active doses: five, 10, 20 and 30 milligrams of psilocybin — body weight adjusted. So those milligrams per 70 kilograms of body weight. We've recently published a paper in our newer trials, dropping the body weight adjustment because going across hundreds of volunteers, we've figured out that you don't need to be adjusting by body weight.

Andrew Huberman:

Interesting. Well, brain size doesn't vary that much between individuals. At the end, this is a brain effect, mostly, probably body as well. So the person ingests the powdered capsule.

Matthew Johnson:

In a little pill.

Andrew Huberman:

Okay, and is it powder of capsule?

Matthew Johnson:

It doesn't take ... 30 milligrams is a small, You could fit it into a tiny little capsule, and it'll take about a half hour, but anywhere from 15 minutes to an hour to kick in, on average about a ha ...

Andrew Huberman:

And you said the dose range was ...

Matthew Johnson:

Most of our studies are looking at, where we want a psychedelic effect, are in the 20 to 30 milligram range. Again, because we have adjusted by body weight and the average American is over 70 kilograms, about 150 pounds, people in fact have gotten more like 40, 45 in a lot of cases, but it's still a small pill. The session day itself, for most of our studies, is not full of task. We really want to look at the therapeutic response. Obviously, if it's a therapeutic study, we want it to be a meaningful experience. Research has found, not surprisingly, that you get a less meaningful experience when you're in an FMRI, or when you're doing a lot of cognitive tasks. We've done some research of that 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 trade-off of what you can do.

Matthew Johnson:

So our typical therapeutic model, which again isn't just limited necessarily to the therapeutic studies where we're trying to treat a specific disorder. It is to have that preparation, so the person feels very comfortable with their guides. I mean, ultimately, what I tell people is, any emotional response, it's all welcome. I mean, you could be crying like a baby, hysterically. 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, hold your shit. Several friends go to a party, they split a bag of mushrooms. It's like there's a social pressure, for good reason, not to be the guy in the corner of the room where everyone's trying to just have a good time and relax, crying about your mother; your other friends are, they're having an experience too, and you're being a drama king and blah, blah, blah, and so yeah, compose yourself, hold your [inaudible 00:33:01]

Andrew Huberman:

I mean, you're doing therapy for people. It's not just about the experience

Matthew Johnson:

Right, and the experience itself is very much shaped by that container, by the environment, and the degree to which one allows it to happen ... One should let go of control.

Andrew Huberman:

Yeah. 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 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 analyst. That relationship becomes a template for trust, more generally, and trust in oneself. It's actually 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.

Andrew Huberman:

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 set of conditions, right?

Matthew Johnson:

Yeah.

Andrew Huberman:

Coarsely, space and time are altered in some way, sense of self. For instance, I might be going to a strongly interceptive 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 ... If I had ... Occasionally I'll pay attention to my breathing, but I'm sort of dilating and contracting 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.

Andrew Huberman:

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 psychedelic, but that's the idea here. Or if I'm paying attention, for instance, to some somatic experience, like the coursing of waves of heat through my body, that I'm not suddenly saying, "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 to me is one of the more unusual aspects to psychedelics, is that normally the social pressure, but also just our internal pressure from our own brain is, "Pay attention to many things at once." Not just one. Is that-

Matthew Johnson:

Especially these days. Yeah. Multitask. Yeah.

Andrew Huberman:

Right. Multitask. And the more that we focus on one thing, the more bizarre that thing actually can appear to us. I mean, even if it's the tip of your finger and you're not taking any psychedelic, you spend a long enough looking at the tip of your finger, you will notice some very weird things.

Matthew Johnson:

I think of that as the classic psychedelic effect, or one classic effect, and one I've used many times of, this example of why people shouldn't necessarily ... One should be judicious in putting themselves in these circumstances. Someone could be 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 their hand and ... their hand is the most amazing miracle. 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. This is what organisms do, this is what we have to do. And it's like there's this dishabituation component that-

Andrew Huberman:

Dishabituation.

Matthew Johnson:

Yes. We wouldn't be able to get through life, we wouldn't be able to cross that street if we were like, "Holy ... This is a miracle!"

Andrew Huberman:

No, I'm so glad you brought this up. I mean, here I'm reflecting my bias as a vision scientist, but most people don't realize this. If you look at something long enough, it eventually disappears. It doesn't actually disappear, but perceptually it disappears. You have these little microsaccades that ensure that it doesn't. But most of us don't look at any one thing for very long. The brain's default is to perceptually jump around crazy with the visual system, with the auditory system. We all ... ADD, people talk about ADD a lot, is sort of baked into our underlying networks at some level and then we can force attention. But it sounds like on psychedelics, one of the primary goals therapeutically is to really drill into one of these perceptual bubbles and expand that bubble. And the safety, it seems, is the safety ... it's sort of a permission to do that without worrying that something's going to happen.

Matthew Johnson:

Right. Because 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. I feel like my heart is going to rip through my chest." I mean she was feeling her ... And I should say, typically cardiovascular response is modest. The pulse and blood pressure go up somewhat. It can be dangerous for people if they're at severe heart risk, and we do ...

Andrew Huberman:

Are you monitoring this the whole time?

Matthew Johnson:

We do. Yeah. We do monitor-

Andrew Huberman:

They're plugged into a variety of devices.

Matthew Johnson:

So every half hour or so we take there, on protocol, and we 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 a certain level, we have a protocol, and we've had to do this only a few times, but the physician comes in, gives them a little nitroglycerin under the tongue and 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 fine, out of an abundance of caution. But someone can feel that, "My God, I'm going to die. I have never felt my heart beat like this before." And the experience of the breath can be just absolutely fantastic. And the breath is obviously interesting because it's this automatic control, but it could also be voluntary, so people can get into a sense of, "My God, what if I ..." It sounds silly, like a stoner maybe-

Andrew Huberman:

What if I forgot to breathe?

Matthew Johnson:

Exactly. But people could ... That can be so compelling. And so one other reason ... Get back to one of your questions, what do we do to allow them to go further into these bubbles? It's like, one is wearing the eye shades. We don't call them blindfolds because that has a negative connotation like being kidnapped.

Andrew Huberman:

Well, and they're probably seeing a lot in there anyway. So blind isn't the appropriate.

Matthew Johnson:

Right, right. That's, I've never thought of it. These should be inner sight shades.

Andrew Huberman:

When you close the eyes, the levels of activity in the retina actually are maintained. It's just spontaneous activity.

Matthew Johnson:

And it seems, and I'd be curious about your thoughts on this, but the way I describe it is that the mind's eye, this kind of loose term we use, can be on rocket boosters. So a lot of times for some people, like a compound like psilocybin, for some people there's no perceptual effect. If they're looking at this room, it would pretty much look the same. Sometimes folks say, "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 ... " On 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 the true hallucinations where you thought you were having a conversation with someone who was never there.

Andrew Huberman:

We will definitely get to those. But 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 idea of manipulating that system, to me, sounds very uncomfortable because the whole idea of ... Well, witches and flying, there was a whole history there 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 there's a lot of mythology around the broomsticks that's complicated, but that sounds very unpleasant. One thing about the serotonergic ... with psilocybin, so there's an expansion of a particular, fairly narrow percept. It could be sound, could be an emotion, could be sadness, could be a historical event or a fear of the future.

Matthew Johnson:

Yes.

Andrew Huberman:

And you've mentioned before that there's something to be learned in that experience. There's something about going into that experience in an undeterred way that allows somebody to bring something back into more standard reality. 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, or giving up control. Because if the experiences are many but the value of what one exports from that experience is kind of similar across individuals, that raises all sorts of interesting questions. And this is not a philosophy discussion. We're talking about biology and psychology here. So let's say I decide I'm going to focus on the tip of my pen. I mean in a psychedelic state, I could fall in love with this pen. I do happen to like these Pilot V5s and V7s very much. But I could feel real love for the pen. That's not an unreasonable thing to expect in a psychedelic journey.

Andrew Huberman:

And in 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 friction that I might have with a family member over my entire lifespan. And yet the export from that, those two vastly different experiences, is one of feeling a better relationship to the world and to oneself. So what does this tell us about-

Matthew Johnson:

How can the pen and processing your childhood trauma both lead to ... Yeah.

Andrew Huberman:

I mean at that level it raises this question, first of all, How? Why? I mean, or just what are your thoughts on that?

Matthew Johnson:

So this is definitely in the terrain we're figuring out. Educated speculation is the best I can provide, but I think the best ... I think the common denominator are persisting changes in self-representation.

Andrew Huberman:

Okay. Tell me more about self-representation.

Matthew Johnson:

That's the way one holds the sense of self. The fundamental relationship of a person in the world. I mentioned earlier that these experiences seem to alter the models we hold of reality. And I think self is the biggest model. That I am a thing that's separate from other things and I am defined by certain, I have a certain personality, and I'm a smoker that's having a hard time quitting, or I'm a depressed person that views myself as a failure. And all of these things, those are models too. And I think that change in self-representation may be an end point for these different experiences. I mean maybe the falling in love with the pen, the whole idea that you're ... Especially in contemplation afterwards, and obviously I'm speculating here, but that whole idea that you could have such a deep connection with this obviously random aspect of the universe could potentially lead to this transformed understanding of the self, and the pen may be a proxy for the miracle of reality in a way that relies nothing, on no supernatural thinking.

Matthew Johnson:

You could be a hard atheist and take this ... Ultimately, Oh my God, like that ... Just like the pen. This is amazing, the fact that we exist. And so there could be an extrapolation chair, and you use the pen, but I think it sounds as similar to Aldous Huxley's classic description in "The Doors of Perception" of the chair and the drapes. He took 500 milligrams of mescaline. He was just-

Andrew Huberman:

Is that a high dose of mescaline?

Matthew Johnson:

Yeah. Yeah. And that's a heroic dose for sure. And he just going off on the chairiness of the chair. This chair is exuding the quality of being a chair.

Andrew Huberman:

This expansion of the perceptual bubble. A narrow percept that then grows within the confines of that narrow percept. 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 in this process we call "interception." And then there's the title of the self, the "I am blank." And I noticed you said that several times, and it's intriguing to me. 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 within the Seal teams. And he's a fairly philosophical guy, also a 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 how you are in the world.

Andrew Huberman:

And the first pass, it sounded to me a little bit like Internet psychology type thing, like "The Secret" or something ... Which frankly I'm just not particularly [inaudible 00:47:17]. So if you like the whole "fake it till you make it," I don't actually subscribe to any of that. But in dissecting that a little bit further with him, I came to realize that these words "I am" are very powerful. I don't think you've reprogrammed your brain just by saying them. But how one defines themselves internally, not just to other people, but how one psychologically and by default defines themselves, I think, is very powerful. 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 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 a tremendous feat of neuroplasticity.

Matthew Johnson:

And I think certainly more work needs to be done. This is the horizon. And I should credit Chris Letheby, a philosopher in Australia, who has a forthcoming book. It might be out right about now or soon within the coming months. "Psychedelics and Philosophy."

Andrew Huberman:

That's the title of the book?

Matthew Johnson:

It might be "Psychedelic Philosophy." It's really close-

Andrew Huberman:

Chris Letheby. We'll put a link to it.

Matthew Johnson:

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, can these experiences, and including those therapeutic effects, be explained from a naturalist point of view? And his conclusion is that the changes in self-representation may be the commonality. Now that could go along with plant spirits, and the Buddha, and chakras and whatever your model 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 of these varieties. So I think there's something about this change in sense of self. It seems to be something on the identity level, both with ... I think of the work we did with cancer patients who had substantial depression and anxiety because of their cancer, and also our work with people trying to quit cigarette smoking.

Matthew Johnson:

I mean, there's this real ... There seems to be, when it really works, this change in how people view themselves. Smoking, really stepping out of this model, "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 button, I can decide not to smoke." And I call these "duh" experiences with psychedelics because people often ... in the cancer state you say, "I'm causing most of my own suffering. I can follow my appointments, I can do everything, but I can still plan for the ... 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 ...

Matthew Johnson:

So it sounds, when it comes out of their mouths, and folks will say ... And this is part of the inevitability of a psychedelic experience. Folks say, "I know this sounds like bullshit and this sounds like ... but my God, I could just decide!" They're feeling this gravity of agency. And which I think is interesting because, regardless of the debates on the reality of free will, I think the philosophy of that, whether there's ultimately free will, 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 the human being has. And that seems to be at times fundamentally supercharged from a psychedelic experience. This idea, "I'm just going to make a decision." Normally, you tell a depressed person, "Don't think of yourself that way. You're not a failure." Look at all the ... It's just, yeah.

Matthew Johnson:

But you can actually ... In one of these states have an experience where you realize, "My God!" Just using MDMA to treat PTSD, and we're going to be starting work with psilocybin to treat PTSD, someone could really reprocess their trauma in a way that has lasting effects. And clearly, there's probably something of those memories. They are altered ... very consistent with what our understanding of the way memory works. So the whole idea — people can actually in a few hours have such a profound experience that they decide to make these changes in who they are, and it sticks. There seems to be something like that.

Andrew Huberman:

And that's profound. I think a few moments ago I made some semidisparaging statements about things like "The Secret" and affirmations. And the reason I do that, 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, 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 and 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, it's very hard to control thoughts.

Andrew Huberman:

So if somebody says, "I can't." And then somebody says, "Well no, every time you say you can't, your brain hears that and it 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. And just fundamentally, you need ... There's 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 give a kid a kitten or a puppy, their first kitten or puppy, and the 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? Likewise, with an adult in a certain circumstances.

Andrew Huberman:

So I think I'm fascinated by this idea that a somatic and a perceptual experience, but a real experience of the sort that you're describing, 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, of treating trauma with these different compounds. I wanted to step from the experience under the effects of the psychedelic. So the person there 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 relived trauma, maybe it's the beauty of 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 psychedelics seems to be in the therapeutic sense, is the ability to truly learn from that experience so that the learning becomes the default.

Andrew Huberman:

That one doesn't have to remind themselves, "Oh I am ... " They don't have to do an affirmation. "I am a happy person." I was thinking of Bart Simpson, like writing on the chalkboard; didn't work for him, doesn't work for this other stuff too. So as they transition out of this state, I know that there's a kind of heightened 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 and the waking state valuable? Because you're in a sort of mishmash of altered reality and new reality. What do you to guide people through the, out the tunnel as they exit the tunnel?

Matthew Johnson:

And I have to say, this is where we need more experimentation. Really the clinical model goes back to literally the late 1950s. And there's been virtually no experimentation on, let's say, randomized people to, "We're going to talk more during the latter half of the session" versus not. Versus we have them write an essay after their session versus not. Versus we have this amount of integration.

Andrew Huberman:

What's the discussion in your studies? Are they writing or talking out as they're doing it?

Matthew Johnson:

And it's called — very loosey goosey term — integration. But for us means as they're coming back from the experience, sort of five, six hours in — so this is the afternoon, they've been dosed around nine o'clock, so this is four o'clock or so. Just some initial, "Tell us about the experience. Do you want to ... " not unpacking it totally. But 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 a few bullet points, it could be 20 pages, and we get everything in that range. But try not to be self-critical. It's not graded. This is just to process and for a point of discussion the next day. So they write something, they come in the next day for a one to two hour, depending on the study, integration session. Basically, let's discuss your experience, and depending on what study it's in, what might that mean for your dealing with cancer, what might that mean for your smoking or becoming a nonsmoker?

Matthew Johnson:

So you encourage them to simply take it seriously. And I think this is, again, is sort of one of the points that could be the antithesis of what some social users use. I mean, this was written about by Huston 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, even if one has this sense of being one with the universe. And it totally shakes their soul so to speak. But the next day their friends were like, "Ah dude, you were screwed up, too much acid for you, wooo! Man, next time you need to have a few more beers to bring that down." This sort of social reinforcement for dismissing the experience. "Oh God, you were talking out of your head, man." Even if it's good natured, but it's this dismissal, it's not like ... What you want to do is, "Tell me more about that. You were crying at one point and talking about your mom. Let's talk about that. What was that? Do you remember that?"

Andrew Huberman:

Are you doing that follow up or they're encouraged to do that in their own life with the various people in their lives?

Matthew Johnson:

Both. So we do that explicitly in the follow-up, where we have these discussions and, depending on what the situation is, you might encourage the person to follow up. Really the basics of it is supportive therapy. Use all the reflective listening and the humanistic psychology thing. Unconditional positive regard for the person. But I think if someone feels inclined to apologize to their sibling about something, it's like, "Yeah. Go ahead and call them up." With something big like a relationship change, it'd 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-

Andrew Huberman:

Do you also tell them not to start any relationships?

Matthew Johnson:

I don't remember that ever coming up.

Andrew Huberman:

I'm not joking, I was just wondering, but makes sense why-

Matthew Johnson:

Like if they're dating and they're thinking like, "Ah, might be time to take it to the next level. Should 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 two?"

Andrew Huberman:

Yeah. Don't get a puppy-

Matthew Johnson:

And let your sober mind-

Andrew Huberman:

Don't get a puppy. Certainly don't get four puppies until you ... I have a question about flashbacks. One of the kind of things you hear is flashbacks and that people ... Do people get flashbacks? And if so, what is the basis of flashbacks? On-the-street lore about this is that somehow some of the compound gets stored in body fat tissues and then released later? Is that complete nonsense?

Matthew Johnson:

No evidence for that. So probably complete nonsense.

Andrew Huberman:

Flashbacks are nonsense? Or the storage in body fat is complete nonsense?

Matthew Johnson:

The storage in body fat. So to answer whether flashbacks are complete 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 appears real that's called Hallucinogen Persisting Perceptual Disorder. It's in the DSM. A certain number of people, very small number of people, percentagewise, who have used psychedelics will have these persisting perceptual disorders. They'll see halos around things. They'll see some trails, after-images following an object in motion. They'll see distortions in 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 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.

Matthew Johnson:

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 in illicit use. So that brings in, "Okay, is there polypharmacology?" Because you're drinking during-

Andrew Huberman:

Did you take what you thought you took?

Matthew Johnson:

Yeah. What's the dose? What's 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 just people who had hallucinogen history. And the amazing thing about this is that a number of people seem to have straight-up HPPD diagnosis.

Andrew Huberman:

What is HPPD?

Matthew Johnson:

Hallucinogen Persisting Perceptual Disorder — who have never taken a psychedelic. So it's often prompted by alcohol, benzodiazepines, cannabis, even tobacco. And I believe in one individual, no lifetime history of any ... It wasn't preceded by any of those substance uses. So I think of it like the precipitation exacerbation of psychotic disorders. It seems pretty clear through observation that some people with either predisposition or active psychotic disease, that this can destabilize them. The same way that a life experience can destabilize this 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. Clinical practice, it ended up in the DSM focused on hallucinogen because I relate it to the psychology of xenophobia.

Matthew Johnson:

It's always the weird other thing that gets the attribution. You don't attribute to the thing, "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." You take a crazy drug and you can get people to believe all sorts of crazy stuff. The biggest example of that is the cathinone derivatives, so called bath salts. And if remember several years back ...

Andrew Huberman:

Yeah. What was the deal with that?

Matthew Johnson:

The guy in Florida that ate the other guy's face. There was a homeless guy that literally ate part of someone's face off.

Andrew Huberman:

While the person was alive.

Matthew Johnson:

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 bath salts stuff that's been going on." The only thing-

Andrew Huberman:

What was it was-

Matthew Johnson:

The only thing in his system-

Andrew Huberman:

Maybe we could set the record straight for people. Why would he say bath salts? And was it bath salts?

Matthew Johnson:

It wasn't. And so the only thing in his tox was cannabis, which we all know, typically people don't eat people's faces off after they get stoned.

Andrew Huberman:

... Hungrier but not that hungry.

Matthew Johnson:

Right. So it's just an example of the xenophobia. Today, if you get on Google images and look up bath salts, one of the most common images you'll see is this poor guy's face being eaten and all. So we're just so ready to latch on, just like the people of another culture that we don't know of. It's very easy to assign attribution to a class that you're very unfamiliar with. So I think the psychedelics 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'd 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 experience is what we call state-dependent learning. It's returning yourself to a similar context can bring back the same thoughts and emotions as the experience.

Matthew Johnson:

So someone used mushrooms a week ago, now they do something like they smoke some cannabis, or they take a warm bath or they're simply relaxed. It 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 ... 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 not typically not perceptual. And then another class are just sort of perceptual anomalies within a day or two following the experience, which is not HPPD. Most people have joked that this is a free trip. You might see a few trails or halos the day afterwards. It doesn't last longer than that and it doesn't screw you up. It's kind of fun like, "Oh yeah, I'm still seeing some trip." Most people will say. So it could mean any of those things.

Andrew Huberman:

Got it.

Matthew Johnson:

So flashback is ... Yeah.

Andrew Huberman:

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, even a trauma, or a wonderful experience or a 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 circuits could take years. We don't know. It's 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 ...

Andrew Huberman:

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 ever reported this. I've never done ayahuasca, which I'm assuming has some overlap with the serotonin system. Probably hits a variety of systems-

Matthew Johnson:

So it's DMT-

Andrew Huberman:

The DMT system or-

Matthew Johnson:

The active-

Andrew Huberman:

Excuse me, that's right.

Matthew Johnson:

It's MAO inhibitors that allow the DMT to be orally.

Andrew Huberman:

Of course, of course. Right, I should have recalled that. Absolutely. Well, I've never done it, but a number of people I know that have done ayahuasca, as well as people I know who have done MDMA, report an increased sense of what is sometimes called ASMR, or these autonomic sensory meridian reflexes, which is ... And it's interesting, a lot of people have these naturally, and they hide these. 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 shiver down their spine or up their spine consciously. Like you can kind of ... 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 in sports camp. I was like, "It's really hot here." And I could actually create a cooled perception.

Andrew Huberman:

I told someone this once and then 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, 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 deeper sense of somatic self. Now on the Internet, ASMR, if you look it up, it's a little bit like the bath salt thing, but in the other direction.

Andrew Huberman:

There are people that pay ... Let's just say there are accounts on YouTube that have many, many millions of viewers of people that will whisper to them about ... For instance, there's people that will go listen to, it seems to be women in particular, whispering about car mechanics, or something, or about ... Or scratching. So 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 deep core of the body. It's the autonomic nervous system down tin the curve of the spine.

Matthew Johnson:

Probably what a certain number of people would call kundalini, which is another one scientifically who-

Andrew Huberman:

Yeah, that's right. And people who do long-duration kundalini breathing sessions, many of them will report later feeling as if their perception of self is outside of their head. That they're literally walking ... It's 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 clinically described neurologic phenomenon.

Matthew Johnson:

Have any studies been done? I would imagine that person might actually ... Would they duck? Oh, what? That would be an interesting ...

Andrew Huberman:

That'd be the kind of thing my lab would want to get into.

Matthew Johnson:

Yeah, their body could clear, but their projection wouldn't?

Andrew Huberman:

Yeah, the sense of self. I mean there's a well-known phenomenon. In a few individuals, it's very sad, where people actually avidly seek out amputation of their limbs because their limbs, they feel, don't belong to their body.

Matthew Johnson:

Oh yeah.

Andrew Huberman:

This is a very sad, and fortunately very rare, but also very sad condition. Anyway, I think the core of this conversation that we're drilling into is this notion of reordering the self. And it's a relief to me to know that flashbacks are not something that is, forgive the term, baked in to the psychedelic experience. And I suppose that's a good segue to ask about other sorts of drugs. Having said "baked in," the temptation is to go to marijuana or cannabis. But if we could, I'd like to just ask about some of the more dopaminergic compounds. In particular, MDMA.

Matthew Johnson:

Yeah.

Andrew Huberman:

My understanding is that MDMA is a purely synthetic compound. That you're not going to find MDMA in nature.

Matthew Johnson:

So far.

Andrew Huberman:

So far.

Matthew Johnson:

DMT was first synthesized in the lab, and then we thought it didn't exist in nature. And then Richard Schultes found it everywhere. So who knows, a plant out there might be making MDMA, but as far as we know now, no.

Andrew Huberman:

Right. And we'll talk about DMT and its sources within the body, but MDMA could exist elsewhere, but it has been synthesized. And my understanding is that MDMA leads to very robust increases in both dopamine and serotonin simultaneously, which from a neural network's perspective is a very unusual situation. Normally, because dopamine puts us in this exteroceptive, looking outside ourselves, seeking things in the world beyond the skin, our own skin; and dopamine, excuse me, serotonin tends to focus us inward. Those are almost mutually exclusive neurochemical states, though they're always at different levels. So why would it be that having this increased dopamine and increased serotonin would provide an experience that is beneficial? And to the extent that 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?

Matthew Johnson:

Yeah, in terms of the effects generally on serotonin and dopamine, I can only speculate. Is that dopaminergic component necessary for, let's say, we know that the amygdala is less reactive under acute effects, and that may play a role in ... There's less control from the amygdala, in terms of one's experience of memory. So it may be part of this reprocessing, this reconsolidation of these memories in a different way, where the amygdala's not going crazy, saying freak out, fight or flight.

Andrew Huberman:

Well I should have said, it seems like MDMA is being used, clinically anyway, mainly for trauma, not just for depression.

Matthew Johnson:

Although part of the ... We really don't know. It may be that MDMA is great for depression and some of these other, and it may be that, and I'm going to be looking at this soon, that psilocybin is great for treating PTSD. A lot of underground therapists say that, underground psychedelic therapists. So we don't really know yet-

Andrew Huberman:

What do you mean by underground? Oh, because they're-

Matthew Johnson:

People doing illegal ... But more like a professional therapist would, it's just illegal. And this is a growing thing. So we don't really know which. Speculating, but it may be that MDMA, for a broader number of people, is better for trauma because the chances of having an extremely challenging experience, what I call the bad trip, really freaking out, is much lower with MDMA. People can have bad trips, but they're of a different nature. It's not freaking out because all of reality is shattering, and it's less of this ... It can take so many forms with the classic psychedelics, but typically you'll hear something like, "I didn't know it was going to be like this." No matter how hard you tried to prepare them, that this is like "Get me off this ride."

Andrew Huberman:

You're talking about LSD or psilocybin?

Matthew Johnson:

LSD, psilocybin, ayahuasca.

Andrew Huberman:

Bad trip

Matthew Johnson:

Yeah, yeah. And just this sense of, "I'm going insane. This is so far beyond anything I've ever experienced and it's scaring the shit out of me. I don't have a toe hold on anything, even that I exist as an entity." And that can be really ... I think frankly, experientially, that's the gateway to both the transcendental mystical experiences, the sense of unity with all things, which we know, our data suggests, is related to long-term positive outcomes.

Andrew Huberman:

Wait, I want to make sure I understand. So you're saying the bad trip can be related to the transcendental experience?

Matthew Johnson:

Right, I think those are both ... Speculating, but you have to pass through this 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 behavior, of how you are within yourself choosing to handle letting go.

Matthew Johnson:

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, through clinical observation, it 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 to the others, because it forces people. There is no choice to hang out in the-

Andrew Huberman:

I've never done it. I was told that DMT is a high-speed locomotive into the psychedelic experience and out of the psychedelic experience. And there's no ability to hold onto the self while you're in the peak phase. Is that correct?

Matthew Johnson:

A lot of people say that, but Terrence McKenna, who's the classic bard on DMT effects, he would say the sense of self was intact. But everything else, the sensorium and what you navigated, what you oriented towards, everything else changed, basically. But it's hard to ... when everything's changing... it's hard to say what is the self that's changing? What is the rest of the world?

Andrew Huberman:

Well, and language is totally deficient to describe experience anyway, much less on a psychedelic. What is McKenna's background? What is his qualification for being this, as you referred, this bard of DMT and psychedelics?

Matthew Johnson:

And we're talking about Terrence, and there's also the brother Dennis, whom I know, who's-

Andrew Huberman:

Can only imagine what [inaudible 01:18:23].

Matthew Johnson:

They're brothers. Terrence passed away years, a couple decades ago now, but he's 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 19, he traveled to South America. And actually on the initial trip with his brother, who was even younger than him, with some other friends and just in search for a DMT snuff that they had read about in the Harvard archives, from the work of Schultes from a generation before. But they had discovered all of these mushrooms growing down there, the psilocybin mushrooms, which they recognized and just took a lot of mushrooms.

Andrew Huberman:

And talked about it.

Matthew Johnson:

Talked about it. And Terrence was basically a very intelligent, very well read, in literature and culture, person. He was the next generation's 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 served, liked Leary, somewhat of an advocate. I mean he would tell people, "Folks, you could see the equivalent of a UFO landing on the White House lawn. It's right there. It'll take five minutes, it'll shake everything in your reality." He would goad people into doing it.

Andrew Huberman:

Well certainly science and clinical medicine are just but two lenses with which to explore these things in life. But part of the reason I ask is, I feel like in the world of health and fitness, you have this very extreme condition of Arnold Schwarzeneggers and bodybuilders who have two percent body fat, and they look like, to most people, they look kind of freakish. Especially now, right?

Matthew Johnson:

Oh, especially now.

Andrew Huberman:

Especially now. And yet-

Matthew Johnson:

Made Arnold look regular.

Andrew Huberman:

Exactly.

Matthew Johnson:

Back in his day.

Andrew Huberman:

And you have contortionists who can put themselves into a small box and wrap themselves into a pretzel. But from those two very extreme subculture practices that, I don't know anything about contortionism really, except that they get really bendy, but it's a community that included a lifestyle practices and nutritional practices, and drug practices. From those very extreme subcultures, there's been an export, which is that weight training is healthy. The general public has done that. Or that yoga is healthy, so contortionism to yoga, et cetera. And I feel like a similar thing is happening in the realm of psychedelics, where it was Leary and Huxley.

Andrew Huberman:

I mean look, I'm from the Bay Area, I'm not far from the Menlo Park VA, where "One Flew Over the Cuckoo's Nest" is basically based on, right, Ken Kesey and those guys. And there has been an attempt at creating this movement toward openness about psychedelics and their positive effects, that 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 it seems like McKenna and his brother are but just two of many people, Michael Pollan, et cetera, who have no real formal training in biology or psychology.

Andrew Huberman:

The other guys who were at universities lost their jobs. They were actually removed from places like Harvard and other universities for their cavalier explorations. And now things are returning. So in the same way that body building led to weight training in every corner gym, men, women and children, and contortionism is one extreme, but people generally think that yoga is a pretty healthy practice, right? These are a matter of degrees. And now here you are inside the walls of a very highly respected university, Johns Hopkins, you're on the medical school side of the undergrad. So in the med school, which is a serious health institution. The question is to me, what are the valuable exports, and where does the extreme lie? I mean, clearly there's a problem with tinkering with reality through pharmacology. And there's a benefit, it sounds like, to tinkering with reality through pharmacology.

Andrew Huberman:

And what's so striking to me is this is the elements of atypical experience. Atypical representation of the self. So for the average person, or for kids that are hearing this, kids that are in their teens, right? I want to talk about, what are the dangers of psychedelics? This is something you don't hear a lot about these days, and it's not because I'm antipsychedelic at all, but what are the dangers? If a kid or adult has a predisposition toward, let's say, psychotic thinking, right, or auditory hallucinations, or is on the Asperger's 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 it be MDMA, LSD, or DMT, that you think are particularly sharp blades and therefore need to be wielded particularly carefully?

Matthew Johnson:

Yeah. So these can be profoundly destabilizing experiences, and ones that ideally are had in a safe container. What are the relevant dangers and what can we do to mitigate those? So there's two biggies. One, and I've already mentioned, it's people with very severe psychiatric illness. Not depression, not anxiety. I'm talking about psychotic disorders like schizophrenia, or mania as part of bipolar disorder. And diagnostically, this has shifted. So it's a little hard to say how many people today with bipolar would've been labeled with schizophrenia back in the '60s when some of this early research, or just clinical observation, was done. So it seems very clear that folks with a predisposition or active disease, they could be destabilized. And so some of the cases that we know, I always think of Sid Barrett, the first singer of Pink Floyd, seems pretty clear, although I think the family-

Andrew Huberman:

I don't know what happened there. I should be; sorry, Pink Floyd fans. The songs are just really long.

Matthew Johnson:

You're more of a punk guy, right?

Andrew Huberman:

Yeah.

Matthew Johnson:

So I've got my foot in a lot of worlds, definitely in part in the Floyd world. But he basically went crazy early on. I don't think his family ever admitted it, but he developed schizophrenia, classic pattern. And he was doing a lot of LSD. But like a lot of these cases, it looked like he was showing all of the signs of some hints that he had that susceptibility before. And often this is hard to disentangle what causes what, because when do people typically, not always, but develop? When's the modal period for first break? It's adolescence, early adulthood. And when do people start playing with drugs? Same exact time period. So it 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, though; it's a big world.

Andrew Huberman:

Do people around those schizophrenics say it's helped them, or just-

Matthew Johnson:

I don't know.

Andrew Huberman:

Because when schizophrenics say things, you have to-

Matthew Johnson:

Yeah, weigh it.

Andrew Huberman:

I mean, with all due compassion and respect for schizophrenia, it's a disorder of thinking. So if they're saying it helped them ...

Matthew Johnson:

How? Yeah, can you trust them? Yeah, I wouldn't be surprised if there was some kernel of truth in some cases. But they're just so ... It seems very clear that the other side is there too. And that if 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 level of risk, before we start doing research to see if psilocybin can help with schizophrenia. 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.

Andrew Huberman:

What about bipolar disorder? Can it be exacerbated by these?

Matthew Johnson:

Yeah. And it may be that the manifestation of people having prolonged psychiatric issues after a psychedelic experience, as atypical as that is, when that happens, it may be that that might be more like a manic episode than a psychotic episode. And that can be a blurry line. And the folklore is that people go on a trip and they never come back. That's clearly not the case, because the drug is metabolized like for anyone else, and the next day there's virtually nothing in their system.

Andrew Huberman:

But it reshapes circuitry. I mean ...

Matthew Johnson:

Right. And I really do think, much like the positive long-term effects, that this class of problems is related to the experience, and the destabilization that can happen from that experience if it's not in the right container. And again, these people are susceptible to ... Some people with that psychotic predisposition, they were 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 someone who's homeless and is coming from all kinds of early childhood trauma. The disease is probably going to be far worse.

Matthew Johnson:

So having a psychedelic experience is like one of those destabilizing experiences. Now, fortunately, it's really easy to identify those people, and we even err on the side of extreme caution by eliminating people with, say, a first-degree relative. In some studies, even a second-degree relative. Given the heritability, there's some increased chance if your brother or your ... Yeah. So in an abundance of caution, even limiting the ... I think eventually, if it's approved for use, FDA use, that we could dial back on that as we learn more. I think it's, again, overly cautious, which is probably appropriate-

Andrew Huberman:

But you're doing early stage clinical trials, so ...

Matthew Johnson:

Yeah, it's the appropriate place to start at this point in time. But if you give a SCID or another structured psychiatric interview with a clinician sitting down with this person for a few hours to delve into their history, you can very reliably determine if this person has either a psychotic disorder, or bipolar disorder, or a strong predisposition. So 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. You jack the dose high enough, and especially in a less than an ideal environment, you can have a bad trip. You even get it in an ideal environment like ours. At a high dose, around 30 milligrams of psilocybin, after the best preparation we can provide, about a third of people will say essentially, at some point, they have a bad trip. And we-

Andrew Huberman:

At some point within the entire journey?

Matthew Johnson:

Right. Now, they could have one of the most beautiful experiences of their life, sometimes, 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, when they're just taking on their own, like a lot of things, they're fine, they get through it. They're more likely to be better off if they're not having to navigate the streets of Manhattan. And if they're with 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, whatever they're on, there, is better than having nothing. So very dependent on context.

Matthew Johnson:

And so the tough thing here 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, you're fear mongering, and you're exaggerating the danger there." So I want to say it is atypical, 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 or they die. They run into traffic, they fall from a height, whether they thought they could fly, or whether they just fell like you can do when you're drunk or you're intoxicated on any substance. Sometimes that's unclear.

Matthew Johnson:

Or gosh, one of the craziest cases was a kid, an 18-year-old or so in Oregon several years back, that just ... He even wrote about, "I want to take the biggest ..." He had done mushrooms before. "I want to take a heroic dose, the biggest dose I've ever taken." He ended up just totally out of it, ended up in a neighbor's house. He was just totally disoriented, disconnected from reality, and the cops ended up killing him. And it was just tragic. Obviously an overuse of force in that case, because he was actually naked at the time. This naked, 120 pound, I think, as I recall, kid that ended up dying. But-

Andrew Huberman:

Well, it's analogous to the reason I used the examples of body building culture. I mean, people there have taken excesses, amounts of anabolics and diuretics and died. Then the contortionist culture, people have put themselves into little plexiglass boxes to do ... At the extremes, you're going to get deaths, and at the extremes ... 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 create extremes through dosage, it seems.

Matthew Johnson:

Right.

Andrew Huberman:

Well this is why I'm such a fan 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 to understand what legality means for a compound like this, right?

Matthew Johnson:

Right. What model, yeah.

Andrew Huberman:

Right. I mean, again, I'll 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, or deciding how much they need to take, right? Like we said, there's yoga and then there's contortion in a plexiglass box and thinking you're Houdini or something. So these are a matter of degrees. Speaking of dosage, I definitely want to ask you about microdose versus standard or macro dose.

Andrew Huberman:

Tell me that I'm wrong, but I'm always a little bit ... I'm micro cynical, if you will, about this term microdose. And the reason is that many people that I know who talk about microdosing are taking dosages of compounds that are very powerful at microgram levels. So the word micro, I think, can be a little bit confusing to people, because microdose implies less than something. It's a mini dose. And yet some of these compounds are tremendously powerful at microgram concentrations. So what constitutes a micro dose and what is the value of so-called microdosing, if any, and how does it differ from standard, or what I can only assume is called macro dosing?

Matthew Johnson:

Yeah. And so LSD would be the prototypical example of that super potent compound-

Andrew Huberman:

How much, what size dosage of LSD, will lead to hallucinations and standard effects?

Matthew Johnson:

So 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, again, thinking you're talking to the person that's not there. Seeing the pink elephant.

Andrew Huberman:

No, it's more like tracers and things like that.

Matthew Johnson:

More like pseudo hallucinations. Right.

Andrew Huberman:

Perceptual blending.

Matthew Johnson:

And some people never get that even 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 one's models of the world, the model of the self. You can consider all of that perception, in terms of truly not sensation, but the perception, the construction of putting together reality. Yeah, yeah, yeah. So the psychedelic effects are typically considered to start for LSD around 100 micrograms. So a 10th of a milligram is 100 micrograms. And so that's-

Andrew Huberman:

So someone taking 100 micrograms of LSD, nowadays people might mistakenly refer to that as a microdose because it's micrograms, but that's actually a macro dose of LSD.

Matthew Johnson:

Right, they might. And that's one of the most common mistakes or situations that people get into with microdosing, is they intend it to be a microdose, but it ends up being a full-blown dose. Now people do, when they're working with LSD and they're microdosing, they'll shoot for something like, say 10 milligrams, something in that range, 10, 20 milligrams of LSD. So a 10th, a fifth, something of your entry level psychedelic dose. People's ability on the street to do this ... I say the street as if they're on the corner, but anyway, outside of the medical profession to do this, it varies as you can imagine.

Andrew Huberman:

And they're not measuring purity or molarity or things like that typically.

Matthew Johnson:

And there's ways to do it. So even if you don't ultimately know the dose that's in the blotter paper of acid, one could at least get a sense of, yeah, having one of those tabs, one of those hits, is a psychedelic experience. They could do something like put it in water, it's 100% aqueous soluble, you could make sure it all gets into solution. And then volumetrically measure, it's going to be homogeneously distributed. So you can take one 10th of that volume of water after it's fully dissolved, and you know that whatever you started with, you're going to have a 10th of that dose. So the people that are more sophisticated will do things like that.

Matthew Johnson:

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. So don't do this at home. But grind it all up so it's homogenous. Because you can have, taking two caps and a stem, hey, this two caps and a stem that this buddy takes has a different potency than this two caps and a stem that the other buddy takes. So people that are in the know will grind it all up into a homogenous 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'll sneak it into the HPLC at their job, or whatever, if they have a little connect.

Andrew Huberman:

Not your lab.

Matthew Johnson:

Not my lab, that's never happened. Seriously, it never happened. 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. But in reality, that's not what people do. They'll take a piece of blotter paper and they get a tiny little pair of scissors, a Swiss Army Knife pair of scissors, and they'll cut up the tab of acid, which is a quarter inch square or something, and they'll cut it up in 10 little pieces. And it's like, my God, you have no idea if it's equally distributed in that media.

Andrew Huberman:

And we can chuckle about it. 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 this stuff, most of them lost their jobs, or were asked to leave through-

Matthew Johnson:

They lost their funding for this research minimally, and they had to move on to other topics.

Andrew Huberman:

That's right. So these are precarious times. I mean, we're at a key moment where everyone assumes that this is all going to be legal in a few years. But I think that that's a premature assumption, frankly. And let's touch on the legality, and some of the things that are happening now. But what is microdosing psilocybin versus the sorts of dosages that you described before in the 10 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 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 ... You need to maintain your ability to make predictions.

Matthew Johnson:

It's that balance.

Andrew Huberman:

I mean-

Matthew Johnson:

Order and chaos. Prediction. You need models of the world. You need heuristics.

Andrew Huberman:

Plasticity is never the goal; or plasticity is never the goal, goal-directed plasticity is the goal, right?

Matthew Johnson:

Right, right.

Andrew Huberman:

Learning a language, reshaping your experience to a trauma, altering the perception of self. But plasticity is a process like-

Matthew Johnson:

Schizophrenia is a lot of plasticity.

Andrew Huberman:

Exactly. Right. It might even be, there's one theory that it's extreme ongoing plasticity, and that's why people never create stable representations of anything. That's a minority view out there. So what's the business with microdosing, and is there any clinical evidence or peer-reviewed published evidence that it works, quote unquote, to make people feel better about anything?

Matthew Johnson:

So microdosing is the aim of taking, again, something around a 10th of what would be an entry level psychedelic dose for whatever compound. So yeah, with psilocybin, usually people, almost never do people have pure psilocybin. One milligram of psilocybin would be in the range of a micro dose. More likely people are going to have mushrooms, so something like a half of a gram of mushroom. A quarter gram-

Andrew Huberman:

I know people that are doing it every day. They're doing this every day. The same way that I take, personally, I'm not recommending other people do this, but I take some, I'm a fan of LC, L-Carnitine lately. I've been experimenting with that a little bit, which is not a psychedelic compound. I take it every day. And that they're taking, that's their supplement every day.

Matthew Johnson:

Psilocybin.

Andrew Huberman:

That's their supplement.

Matthew Johnson:

Yeah.

Andrew Huberman:

So...

Andrew Huberman:

[inaudible 01:42:01] every day. That's their supplement.

Matthew Johnson:

Yeah. The claims are, and there are a number of them, there's two general ones. One is sort of acting in place of the ADHD treating drugs, so the psychomotor stimulants, so a better version of Adderall. The other claims are essentially a better version of the traditional antidepressants, a better version of Prozac.

Andrew Huberman:

People are taking both for attention deficit and for depression.

Matthew Johnson:

And the aspects of those disorders that we all have a degree of, just like amphetamine, is going to increase the focus at the right dose of anyone who takes amphetamine, pretty much whether you're ADHD, diagnosed or not, the idea is that there may not be necessarily a clear divide between the therapeutic need and positive psychology, even improving mood and focus. So it's not necessarily correcting ADHD but improving focus to supercharge your life. And so those are the claims. I am ... So none of the peer-reviewed studies that have much credibility, none of them have shown a benefit and they've tried. Now, there's only at this point, four or 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 takings psilocybin truffles, basically same as mushrooms. It was more like the roots, the mycelia ...

Andrew Huberman:

Microdosing them?

Matthew Johnson:

Well, taking what would be considered a microdose and then doing some cognitive measures before and after. And the types of things that a lot of cognitive measures are measured on, the order of reaction time and milliseconds. And the types of effects you get, as you could imagine, are ones that would be, you would totally expect could be there from either a practice effect or an expectancy effect, a placebo effect. So for something like these claimed, you can imagine a sort of an increased focus enhancement of cognition. These are 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've 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 ...

Andrew Huberman:

You have to function ...

Matthew Johnson:

In your work life ... Which is the way people are claiming to use that, it helps them be a better CEO. Like you want an accurate sense of time. So if anything, the data suggests that it makes it a little bit less accurate, and there's evidence that someone feels a little bit impaired and they feel a little bit high. So in terms of ... You call that abuse liability and research, not surprising, you take a little bit of a drug that can result in some type of a high and you take a little tiny bit of it, you'll feel a little bit high. So far no studies have shown any increase in creativity, enhancement of any form of cognition or a sustained improvement and mood. Now, no studies have actually looked at the system of microdosing that the aficionados are claiming, and there's a couple of models out there, but folks like Paul Stamets and others, they'll have particular formulas.

Matthew Johnson:

They're 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 whose model is what, but it's always something like that. Some pattern of use, usually not every day. And the claim is that it's not just, sometimes people get benefit that first time when they take it, but they really say you need to be on it for a while. A few weeks in, you may start to notice through this pattern of using it and you're feeling the benefits on those off days, like the three or two days in between your active doses.

Matthew Johnson:

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 field, let's say we as the scientific field have not done the studies to really model what the real aficionados are claiming, where the therapeutic benefits come from. That said, it's almost assuredly there's a good amount of placebo there, but the caveat to that is almost everything in medicine or therapeutics is going to have some degree of placebo there.

Andrew Huberman:

Sure. Belief effects are ... I have a colleague at Stanford, Alia Crum, who has published really beautiful work on belief effects that show that essentially you give the same milkshake to two people. [There] are two groups of people. You tell them that one contains a lot of nutrients, the other is a low-calorie shake, the insulin response ...

Matthew Johnson:

Amazing.

Andrew Huberman:

... varies dramatically between the two groups 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. And I think that these belief effects boil down to all sorts of kind of networkwide neuromodulation, things of that sort of thing.

Matthew Johnson:

And then the work at Harvard suggesting that even if you don't have deception, you give a placebo and say this is a sugar pill, and tell them that and it could still treat things, I think irritable bowel was the first thing they looked at. And so there's a huge reality there. There's a necessity in developing drugs to make sure it's not only that, but in the actual practice of medicine, hopefully what you're always getting is some underlying direct efficacy plus the placebo that enhances that. Now it could be ...

Matthew Johnson:

The real question is, Is the microdosing, are those claims a hundred percent placebo or are they only part placebo and part "real" effect? 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, because of the suffering with depression. 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 perhaps a better SSRI, a better Prozac, which need more tools than fewer tools in the toolbox.

Matthew Johnson:

And it shouldn't be that surprise. Even before, going back to the tricyclics and the MAO inhibitors going back to the '50s, like augmenting extracellular serotonin in one way or another for many people leads to a 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, if there's anything real, it is in that category. Although I'm very open to maybe there is something to the creativity, to the improved cognition, which covers many domains in and of itself. But my greatest hopes are on the antidepressant effects. That said, in the big picture, 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 in depression months later and in addiction over a year later.

Matthew Johnson:

And with these people dealing with potentially terminal illness. I'm interested in big effects, and I don't think you're ever going to get the really big effects. There's also some concern that almost all of these, the more common psychedelics, even counting MDMA, they have serotonin 2B agonist effects, and agonizing serotonin 2B has been shown to lead to heart valve formation problems, morphology issues, so valvulopothy. And so this is why fen-phen was pulled from the market.

Andrew Huberman:

The diet drug.

Matthew Johnson:

Yes.

Andrew Huberman:

Very effective diet drug.

Matthew Johnson:

Right. And it was the portion of that combination that had the serotonin 2B activity that was the problem. And so we don't know, so all of the toxicologists I've ever spoken to about this would say, and 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."

Matthew Johnson:

But the idea of taking something like twice a week for years, I mean even the hippies back in the '60s weren't doing that, right? There's not even these natural ... And even if there was some heart valve disease problem that stemmed from psychedelic use, who's connecting those dots? That's not showing up in the clinical charts for anyone to figure out. And just theoretically, there is more of a concern if something's going to happen with heart valves, it's more likely that those issues would arise when someone's taking these things like, 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.

Andrew Huberman:

Right. Yeah, it's something I hadn't heard before that ... "micro" sounds safer, microdosing as opposed to heroic or macrodosing. And yet, in the context of your lab and other labs doing similar work, you've got people checking blood pressure, you've got people that are really monitoring your psychological and physical safety. When people are out there microdosing, it sounds like there's the potential either through this serotonin 2B receptor or other mechanism that maybe there could be some kind of cumulative negative effects. And I think that's 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 maintains some degree of plasticity throughout the lifespan. The year 25 — not 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.

Andrew Huberman:

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 ... It's plus or minus whatever it is a year or two, but depends on the individual. However, 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 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 and bipolar symptoms in some people, is there heightened risk of that? What's the story with age of use and psychedelics for therapeutic purposes?

Matthew Johnson:

There's no formal research. Although, 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 they want to see those studies.

Andrew Huberman:

Before ...

Matthew Johnson:

Well, not before it's approved as necessarily as for adults, but they're going to eventually want to see in fact, so the MAPS group that's developing MDMA for PTSD, they've already signaled, that's kind of on the list of interest. And there's even some incentives in the FDA pathways for incentivizing folks to explore that use in young people. I know in some of the work that I helped with in pushing psilocybin into phase 2B clinical research, the FDA said, "Well, why can't you give this to kids? Are you aware that depression is a problem with adolescents?" And it's really interesting because FDA is very concerned about pseudospecificity. The idea that ...

Andrew Huberman:

Define pseudospecificity?

Matthew Johnson:

You put out a drug and say, "Oh, this is good for men but not women. This is good for black folks but not white folks." And sometimes there's a very good rationale for that when we're talking about hormones and for specific ... men versus women. And there's certain issues, certain disease states like maybe sickle cell anemia, that's more relevant.

Andrew Huberman:

Tay-Sachs, things like that.

Matthew Johnson:

Yeah, exactly. 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, much like the emphasis at NIH with rodent studies and human studies, that you can't just say you're studying men, or just you need a rationale if you're only ...

Andrew Huberman:

To be clear to people. There's a recent switch, 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 to receive funding, you have to do studies on both males and females of that species, including humans.

Matthew Johnson:

And at least, even if you're not powered for it, at least looking at that in exploratory analysis. As a grant reviewer, I'm charged with looking at, you know, did they address sex as a biologically relevant variable? Anyway, you throw it in there ...

Andrew Huberman:

Does the same drug have different effects in males versus females?

Matthew Johnson:

Right. And you could at least look at the trends, even again, if you're underpowered to look at those between subject type effects.

Andrew Huberman:

Which is a great shift that didn't exist 10 years ago. Sounds like we're both on grants panels. As study section members, you didn't have to do that, now it's an important biological variable. If you don't look at that, you essentially won't get your funding.

Matthew Johnson:

And age is a similar thing. So it's a whole idea, man, if something could help kids, 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 of a cautionary approach. It's probably going to be, certainly whatever disease states are looked at are going to have to be probably treatment resistant, at least as a first step.

Andrew Huberman:

Suicidal depression.

Matthew Johnson:

Yeah. And so all of that in the mix. But hey, if this stuff really helps people that are 25 or 30, what's the rationale that it won't help a younger person? And there are these generic kind of concerns about the developing nervous system is more susceptible to ... I mean, it cuts both ways because it's also more plastic, generally, and adaptable, maybe resilient to injury in certain ways. But you know, hear the rhetoric about kids, their brains and drugs, and it's like the developing brain is a special concern. But I think we're going to be seeing research eventually.

Andrew Huberman:

It's interesting. I went to the high school that is infamous, sadly, Gunn High School for having the highest degree, at least at one point, of high suicide rate.

Matthew Johnson:

Wow.

Andrew Huberman:

Very large number of suicides. This was written up in the Times and elsewhere.

Matthew Johnson:

Is it a very academically successful school?

Andrew Huberman:

It's a very academic ...

Matthew Johnson:

There's a lot of high pressure.

Andrew Huberman:

Very academically demanding school, to the point where they've restricted, the kids will meet often at 6:30 a.m. or 6:00 a.m. before school for study groups and things of that sort. So some of it may relate to that. But I have to say that even prior to all that academic pressure, when I went there, the pressure wasn't like that. We had an unusual number of suicides for whatever reason. And so the idea of kids being prescribed, and I want to reemphasize prescribed, not just using, but prescribed psychedelics for therapeutic purposes I think might make some people baulk. But the idea of kids killing themselves should also make people baulk. 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.

Andrew Huberman:

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 prescription purposes? So medical doctors, MDs prescribing it legally for therapeutic purposes. That's the first question.

Andrew Huberman:

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 too long ago, it is now decriminalized is what I was told. Double-check, people, but what does that mean? And then the other issue and the third question, and 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 psychedelics 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, will psilocybin become a taxable thing just like marijuana? So let's start with the question of what is going on in the U.S. legally? Is it illegal to possess and sell and use these compounds? My understanding is you can still go to jail for having these compounds in your possession or for selling.

Matthew Johnson:

So even though 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, whether the city or state has decriminalized, and that word itself can mean many things. So some forms of decriminalization is close to what folks would call legalization and others are pretty weak. Just saying we suggest that the police make it their lowest law enforcement priority, that type of thing.

Andrew Huberman:

Turn the other cheek.

Matthew Johnson:

Right. But even, the cops can still choose to.

Andrew Huberman:

But someone could get pulled over for one thing, searched, and then by definition, if it's illegal and they find it, then they have to do something about.

Matthew Johnson:

And that'll probably be determined by both judicial precedent — is it going to be thrown out, and just the local prosecutor even before, are they going to choose, even at postarrest are going to pursue to really go after those charges, make those charges stick? So I think that's still in play and is going to depend on the municipality. But like cannabis, federally, these are all schedule 1 compounds.

Andrew Huberman:

Which means they're illegal.

Matthew Johnson:

Which means they're illegal. The caveat to that, just as has always been the case since Prop 215 in California with cannabis in '96 is that, hey, 99% of drug enforcement is done at the local and state level. The DEA, which is the federal level law enforcement, is a tiny fraction of the arrests that ... I mean most people that are arrested for any drug are done by local or state level authorities, but it's still technically illegal. And so you can, and they could potentially, depending on the ambiguity of the local law, even those local officials could charge you with a federal crime. And theoretically the feds could always come in. Now, although, again, a similar case with the whole cannabis history, the feds came in the early days with the folks that were basically highly visible. They went after Tommy Chong for selling bongs. But I remember him being on "The Tonight Show" one time, and I think it was back in the Jay Leno days, he says, "Oh, along Santa Monica Boardwalk, every shop sells bongs. How did you go to prison for a half year for bongs?"

Andrew Huberman:

Because he was famous.

Matthew Johnson:

'Cause he was Tommy Chong, and there were some high profile cannabis groups that were distributing it and were very vocal. Those were the ones raided 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 this initiative in Oregon, which is a state level legalization of psilocybin therapy, which is really interesting. Part of their plan for two years is to figure out how to integrate with the federal level. And I don't know how that's going to go because 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 that could be very, hey, you change administrations ...

Andrew Huberman:

And this is psilocybin by a prescription from a medical doctor, or you're talking about therapists who have master's degrees or PhDs or self-appointed coaches, or something like that, administering psilocybin but without any oversight?

Matthew Johnson:

This is all getting figured out in the Oregon case. And again, there's that two-year period of basically we're going to figure this out.

Andrew Huberman:

What is it with Oregon?

Matthew Johnson:

They're ahead with a lot of ... Euthanasia ...

Andrew Huberman:

I love the state of Oregon, but it's interesting how you have these pockets, Oregon, Vermont seems to be one, you get these kind of pockets where people are experimental with plant compounds. They seem to be green woodsy areas, at least in my mind. But there's sort of a culture around plants and the use of plants as therapeutics.

Matthew Johnson:

And combine that with the West, just more geographically of the antifederalism. I mean the Oregon ranchers from several years ago that held up whatever wildlife place, and that was a big showdown with the feds, and the West is kind of known for more of those issues. So you combined the two: hippie-dippie California-Oregon vibe with ...

Andrew Huberman:

Although, I would argue it's becoming less hippie-dippie than ... Although it was. There's always been a tradition, not just in the culture around drugs, but certainly in academia and in tech, et cetera, that the West has been a place where people have tried to throw off traditionalism, and kind of lineage, and who your parents are, what school you went to and the past as a determinant of what's next and exciting about the future. Whereas, and here we are, an East Coast institution guy and a West Coast institution guy. I think that it's this idea of innovation and the future versus do we stay grounded in history and tradition. And of course there are great institutions on both sides. What's interesting is that Hopkins, Johns Hopkins Medical School, I think of as a real East Coast academic institution. It is on the East Coast. But here you are doing these very pioneering and important and exploratory studies in ... certainly not a hippie-dippie environment, right?

Matthew Johnson:

Oh, yeah. Very conservative psychiatry department. Even among psychiatry departments, and as a psychologist in a psychiatry department, psychiatry is certainly more conservative than psychology, even within academics. But even amongst psychiatry departments, it's a very conservative department.

Andrew Huberman:

So we've 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 for consumption and ...

Matthew Johnson:

Life coaches.

Andrew Huberman:

The life coaches and the general public. Cannabis, I'm not a pot smoker, it's never appealed to me, that's just me and my pharmacology. But you can buy cannabis most places in the U.S. without a ton of risk, it seems.

Matthew Johnson:

Right.

Andrew Huberman:

Are we going to see a time in which you can essentially go into a shop on Abbott Kinney Boulevard in Venice, California, and right now you can go buy marijuana if you have a marijuana card, that's my understanding. I see a lot of people going in and out of these stores. The police certainly have no problem with it. Is there going to come a time where people can just go buy psilocybin?

Matthew Johnson:

They do in Amsterdam.

Andrew Huberman:

Do you think that time is coming?

Matthew Johnson:

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 large spans of time, really in a hundred years, are we going to be doing this 500 years? How could that, it's not going to be sustainable.

Andrew Huberman:

But in five years for instance.

Matthew Johnson:

So I don't think so in the United States. I do think eventually you're going to see something like that, because there's going to be no way. And I think, 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 could imagine what one day regulation, smart regulation might mean for psychedelics. Maybe it could mean that there will be, whether or not you have a diagnosis of a problem, that it may be that even for personal exploration, you can do this legally, but you first have to maybe take it to court, get a ... and I'm not the first to say this, but get equivalent of a driver's license.

Matthew Johnson:

You have to go to get some sort of training, maybe your first number of experiences need to be with trained guides who can facilitate it. And then the public health information for anyone using this, that this is what risk your use is, all use is going to have risk. This is what risk your use is. This is less risky use. These are the factors. So I think eventually we're going to be get... for any... But I would say the same thing for methamphetamine and heroin and cocaine, all of these drugs, it's hard to imagine the current approach of just feeding a black market and really exasperating a lot of the harms from drugs that happens under the current model, it's hard to imagine that maintaining ... That isn't to say I think it should be in all of the 7-Elevens, sold to kids, at the other extreme.

Matthew Johnson:

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 trajectory of the medical research right now would still need to happen. If it's effective as an antidepressant, we need it to be ... There's all the evidence suggesting that whatever disorder we're talking about, the efficacy's going to be increased, and the risks are going to be mitigated drastically. And the types of models we're 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 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.

Matthew Johnson:

They say, "You guys want to keep it only 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 I've done plenty of survey research of 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 helped with their depression, or it's helped with them overcoming alcoholism. 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 safer. So we need to be pushing that. And my best guess is that MDMA is going to be approved within the next three years and ...

Andrew Huberman:

For prescription by a physician?

Matthew Johnson:

Yes. And not just take two and call me in the morning. But in the clinics, the way that 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 going to be questions ...

Andrew Huberman:

Right, because approved and legalized and regulated — 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 and use MDMA without legal consequences. And I do not think that's going to be the situation.

Matthew Johnson:

That is not going to be the case.

Andrew Huberman:

It's not the way it is. And I will say that I think the "psychedelic community," they've been doing what they want to, and will carry on doing what they want to anyway, right? It's not like the legal status has prevented them from doing what they're doing. In fact, unlike Timothy Leary and Huxley and some of the others that were very vocal and lost their jobs, and some who even went to jail, et cetera, I mean, you got a lot of public figures now, like McKenna and others, who are just basically out there talking about psychedelics.

Andrew Huberman:

Michael Pollan, who is more of a writer-foodie guy, gone psychedelic dabbler-writer guy. I know he's kind of a polymath, but the legal status didn't seem to hinder their, at least online careers. I don't know. I haven't looked at their bank accounts, but I'm imagining they're doing just fine. So the fact that work is happening inside of big institutions, I think it's important that you point out, and I'm just trying to underscore — 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 context in a really controlled way, which I think it's a really important mission.

Andrew Huberman:

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, 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. It's construction workers. And if you've ever seen the helmets that construction workers wear, I mean ...

Matthew Johnson:

The jackhammer, oh my God.

Andrew Huberman:

The jackhammer ...

Matthew Johnson:

How could that not be just ...

Andrew Huberman:

Yeah. I have a colleague that works on this in bioengineering. And when you look at the ... 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 athlete or something of that sort.

Matthew Johnson:

And if they're not doing the construction, someone else needs to do it.

Andrew Huberman:

Someone else has to do it. Right. And for some reason, and I too, it didn't occur to me until I heard it, the people who are doing construction, and then of course with bike accidents and falls and things like that as well.

Matthew Johnson:

Military.

Andrew Huberman:

Military, absolutely. So what do you think is the potential for these compounds, particularly 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?

Matthew Johnson:

Yeah, so this is definitely on the more exploratory end. So it's based upon ...

Matthew Johnson:

... on the more exploratory end, so this is based upon the improvement of psychiatric disorders like depression, or depression and anxiety associated with a terminal illness, or a substance use disorder, the addiction. Those are sort of psychiatric disorders. There are anecdotes of people saying that psychedelics have helped heal their brain. 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, improved their memory, including improved their mood. But it's kind of more of the cognitive function, things like memory are ... Now, caveat is if you've successfully improved someone's depression, you can get some cognitive improvement too. But that's a more of a weaker, more indirect effect.

Matthew Johnson:

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 postacutely, so after, in the days following the administration of psychedelic compounds, a variety of psychedelic compounds, and even some nonpsychedelic structural analogs, that you see these different forms of neuroplasticity. The growth of dendrites and new connections being formed with different neurons. Those effects may be at play in the psychiatric treatments that we're dealing with, we don't know that. It seems like a decent guess, and we're going to be figuring out whether that's the case.

Matthew Johnson:

But another potential that that sets up is that maybe that's what's going on with these claims of improvements from neurological issues, that there's actually a repair of the brain from injuries underlying things, situations where there's repetitive head impact. Perhaps there's a potential for helping folks recover from stroke and disorders like that. There's a wide variety of disorders now. It's a bit of magic and a bit of ... It's something that the enthusiasts kind of can do some hand-waving and claim that this is already known.

Matthew Johnson:

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, MMA athletes in the UFC who have been exposed to repetitive head impacts like a lot of sports expose people to, and who are retired from the sport, and are suffering from say depression, which can in part result from 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 improvement and cognitive function and associate like using MRI to see if it affects gray matter over time. These types of things, to see if there are actually some evidence of this improved ... This more direct repair of the brain. But again, it is very like ... we've got some rodent data, we've got some human anecdotes-

Andrew Huberman:

We will acknowledge it's early days and we look forward to seeing the data. I appreciate how cautious you are and 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 in 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, aka neuroplasticity.

Andrew Huberman:

We know that reordering of neurocircuitry in the adult requires these things like intense focus followed by rest, et cetera. But the basis for that, beneath focus is a mechanism, rather beneath the bin that we call deep rest is a mechanism. And those mechanisms are neuromodulator driven. To me, I'm not reviewing your grant, but from a rational perspective, it seems that drugs that increase certain neuromodulators, like serotonin or dopamine, 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 depression.

Andrew Huberman:

The rationale is really strong. I think that's a very exciting area. I get asked all the time about TBI and traumatic brain injury, and right now there isn't a whole lot that people can do, and people are dabbling in the space of hyperbaric chambers, and people do sauna and breathwork, and people are clipping at the margins of what really is a problem that resides deep to the skull. I think I just want to applaud the exploration. I think it's great, provided that exploration is being done in a controlled way. It sounds like that's what you're doing with the UFC. Great.

Matthew Johnson:

Yeah. They were really gracious and had myself and a few of my colleagues out to their headquarters in Vegas.

Andrew Huberman:

Impressive place, right?

Matthew Johnson:

It's in process. There's a dialogue going on there. I'm hopeful that there's going to be some work with them, but it's in process now, in terms of exploring it. There's a real interest, and I'm just really impressed by the organization and their commitment to athlete health.

Andrew Huberman:

I am too.

Matthew Johnson:

We'll see.

Andrew Huberman:

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 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 commonly comes to mind, because they haven't been particularly verbal about it in the press. But I think it's great they're bringing in academics. I mean, geeks like us going out to the UFC performance center. I mean you do MMA, but I'm basically just a geek walking through the place.

Andrew Huberman:

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 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, exploring compounds only in terms of their negative effects, which is where-

Matthew Johnson:

Yeah. NIDA, which is where I've gotten all of my NIH funding over my career.

Andrew Huberman:

Which is so interesting and it's a super important institute. I want to be clear, there are amazing people there. But philanthropy and foundations have been very important in supporting pioneering research. And so maybe we'll just talk a little bit about that. Your lab receives funding from taxpayer dollars through the National Institutes of Health. Is that mainly where your funding comes from?

Matthew Johnson:

Our group has gotten some funding from, 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. Of course when you do a study though, you can show ask [inaudible 02:25:03]

Andrew Huberman:

Show us how they're bad.

Matthew Johnson:

Right. But when you're doing that, you can explore the good stuff too. But the large majority of the work and the most interesting work has been funded by philanthropy-

Andrew Huberman:

Private philanthropy.

Matthew Johnson:

Now, I still have some grant support from NIDA outside of psychedelics. I'm shifting more and more of my time towards focusing only on psychedelics, and in fact, us getting the center level funding from some really big-picture philanthropists helped me to start to make that transition. But groups like the Heffter Research organization, Dennis McKenna, [who] is one of the founding members — the brother of Terence McKenna — who's, by the way, an ethnobotanist. That's what his PhD is in.

Andrew Huberman:

What does that mean, an ethnobotanist?

Matthew Johnson:

Studying essentially the anthropology of psychoactive plant use.

Andrew Huberman:

You can get a degree in that?

Matthew Johnson:

Yeah, yeah. Hanging out with cultures and studying their use of these compounds in the traditional ways.

Andrew Huberman:

At Hopkins? That degree exists at Johns Hopkins?

Matthew Johnson:

I don't think that degree exists at Hopkins, but I mean the kind of the most ... As you know from academia, sometimes folks, I'm not sure how many people's PhD is actually in ethnobotany or-

Andrew Huberman:

I've never heard of it before.

Matthew Johnson:

... it's actually in something else. But the real focus is, my degree is general experimental psychology.

Andrew Huberman:

Ten thousand kids out there just decided they're going to major in ethnobotany.

Matthew Johnson:

I mean one of the pioneers of the psychedelic era, before Leary, and actually he was late even for the human researchers, folks like Humphry Osmond and Abram Hoffer and Sidney Cohen were earlier. But even before those folks, Richard Schultes at Harvard — I mentioned him earlier in the conversation — discovered all of these various tribes using ayahuasca, or yagé, a different name for the same thing, throughout South America, and these DMT-containing snuffs, and all of this; that was ethnobotany, this kind of intersection of anthropology and these psychoactive plant compounds.

Matthew Johnson:

The Heffter Research Institute, which Dennis is a founding and active member of, 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 Feilding, has been the head of; they provided the first funding for our psilocybin smoking cessation research. And the Heffter came in and provided subsequent funding. And then there are other groups like Council on Spiritual Practices. A great guy 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 understanding, these people take these compounds and, astonishingly, frequently will say, "That was the most important thing I've ever experienced. What the hell is that?"

Andrew Huberman:

I had someone mention recently, I think this might surprise people a little bit, it certainly surprised me. I had a friend who adores his children, he's got three children, he adores his children. A happy marriage and great, great father, they're both great parents. And he told me that as part of a clinical trial, he had a DMT experience that he claims ... he said, "I'd love to tell you that the birth of my children was as profound, but that was a more profound experience than the birth of my children. Any one of them and all of them combined." And I was like, wow. Now I've never done DMT but I was like, wow, that's a pretty strong statement. Now he did it in the context of one of these clinical explorations. I assume that was part of a legal clinical trial. But I mean that's saying something. It's saying something. I mean he's a very rational, very grounded guy otherwise, but ... so philanthropy foundations. And then-

Matthew Johnson:

Most recently, so sorry because I can't skip it. Our center level-

Andrew Huberman:

Yeah, you can't skip it. You can't skip [inaudible].

Matthew Johnson:

... funding which came a year and a half. I mean the Heffter 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. The same thing with the MAPS organization, more on the MDMA side, holding that candle during the darkest years. But smaller organizations connected to smaller ... But growing over time, pockets of wealth. But we basically limped along on a wing and a prayer until recently when we got the $17 million 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. It's a capital investment, staff, equipment, salary support, which has always been the huge thing for us.

Matthew Johnson:

But the $17 million gift, which was split between the Cohen Foundation, so Steven and Alexandra Cohen, they covered half of it. And the other half, the Tim Ferris collaborative; basically Tim and a few friends ponied up, divided the rest of that, half of that $17 million gift and came together to just ... I mean, it's completely transformed the work that we've done and our ability to fully delve into this area and not worry that, "Oh, if I focus on this rather than putting another three NIDA grants on some other topic that may or may not get funded, if I focus too much on the psychedelics, am I putting my career at jeopardy?"

Andrew Huberman:

You're not only a tenured professor, you're also a full endowed ...

Matthew Johnson:

Right. So that came-

Andrew Huberman:

By the way, when you say somebody is a fully endowed professor, want to be very clear what that means. That means that there's funding-

Matthew Johnson:

It might mean all of the above, but no.

Andrew Huberman:

I have no knowledge of your particular situation, but you probably do.

Matthew Johnson:

Just kidding.

Andrew Huberman:

Sure. 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, there's no reason why they would understand all the nuts and bolts of how this works.

Matthew Johnson:

Academia is weird.

Andrew Huberman:

Academia is weird because we're not talking about increasing, we're not talking about an endowment or 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 nobody goes into science for the money, at least not at the academic level, not in academia. But allows people to devote more of their time and energy to these exploratory realms like psychedelic research or, in the case of my lab, the work that we're doing with David Spiegel's lab on respiration, breathwork and hypnosis for moduling 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 NCCIH, which is complementary health.

Matthew Johnson:

Used to be INCAM.

Andrew Huberman:

Yeah, and then NIH.

Matthew Johnson:

They changed their name.

Andrew Huberman:

And now we're not just throwing out acronyms just to bat back and forth acronyms, but I think 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 exist. The solutions are going to involve behaviors that are going to 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 powerful levers, it sounds like.

Andrew Huberman:

And I just want to say that I think the reason I reached out to you and am 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. It's so time-consuming and painstaking. And you've made real progress. I mean, you guys are publishing papers. There's a new dialogue emerging that isn't just books on bookshelves and psychedelic psychonaut gurus on the Internet, who also play an important role. But you are really moving this field forward. And I know there are others as well. There are colleagues in England, and others as well. We acknowledge them.

Andrew Huberman:

But I just want to say personally that I'm 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 and you got ligand." 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. I know I'm speaking on behalf of a ton of people now, and in the future, that 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 a really special and unique thing.

Matthew Johnson:

I appreciate that. I had a good colleague, in fact we shared some grant support under the multi PI system years ago, and she actually took a job at NIH as a review officer, and I remember her telling me... And she actually left when she had multiple R01s, so it's like she didn't [inaudible 02:35:25]

Andrew Huberman:

R01s are kind of the bread and butter big-

Matthew Johnson:

The big-fish grants.

Andrew Huberman:

... grants that every card carrying ... It's a mark of respect in our community to have one or several of these. Yeah.

Matthew Johnson:

Yeah. And it's like you eat what you kill in academia. It gets to what we were 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 ... The university doesn't pay you your salary. It goes through them.

Andrew Huberman:

You're just able to do more work.

Matthew Johnson:

And if you don't pull in the grants to cover your salary, your job can come to an end. Even if you're tenured at a place like Hopkins, they can do tricks like slowly lower your salary over these [inaudible 02:36:06]

Andrew Huberman:

Or they just escort you ... Or they just take away your space.

Matthew Johnson:

Yeah, they put you in a closet and give you no support for trainees and basically make life hell for you. You could drive a cab in Baltimore and call yourself a full professor at Hopkins, truthfully, but you may have no ability to get anything done.

Andrew Huberman:

I'm sure they're out there.

Matthew Johnson:

But yeah, I remember one of the things this colleague 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 connected to drugs, also connected to aging. But she said, "I don't feel the impact of what I'm doing in the real world." And it's unfortunately there for a lot of academia. What we do, it stays in the ivory tower, the world is-

Andrew Huberman:

Not anymore.

Matthew Johnson:

It's a beautiful but messed up place, and a lot of this doesn't disseminate. And because of the various structures, the way the world is set up, and thankfully this ... I mean, because of the work 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. It's upping the ante. 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.

Matthew Johnson:

But we've 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 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 ... early research is saying it shows a high potential for treating disorders that don't have very good treatments. And we're probably, again, a few years away from both MDMA, and probably a year or two after that, psilocybin being treated for PTSD and depression respectively. We have to wait for the phase 3 studies. But if the results hold up, even if the effect size is halved of what we're seeing now, it's still going to be a lot larger than what you're seeing with the traditional medications. And so it's going to be approved if the data hold up, and it probably will, from my judgment.

Matthew Johnson:

I feel like what I'm doing is actually having a positive impact in the world, in a way. And I feel lucky that I got interested in an 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 mean, I was lucky to be interviewed on "60 Minutes" because of this work, and I was like, "Oh, my God, I know so many ... " there's a bit of imposter syndrome. Like, oh, my God, I know so many scientists that deserve, more so than me, to have that level of exposure.

Matthew Johnson:

But if you happen to be in that place where ... you've 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 I've been lucky, but also did take a bit of a leap of faith early on. I did have some advisors that told me, "You've got a really promising pedigree early on. Are you sure you want to focus time on the psychedelic stuff?"

Andrew Huberman:

Yeah. You've embraced risk. I think the world's changed since, in 2020 certainly. But channels like social media, podcasts and things of that sort, your exposure is because people are interested in these topics. And that's why people like myself are interested in talking to you. I mean at Stanford there are now a few labs starting to explore psychedelics more at the mechanistic level, so in animal models, excellent labs. But also I can imagine because of the pioneering work that you've done at Hopkins, it'll start to become more common.

Andrew Huberman:

I'm certain that people are going to have questions about how to get in contact with you and learn more. If people have trauma, PTSD, depression, 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, its @drug_researcher. Correct?

Matthew Johnson:

Right.

Andrew Huberman:

Okay.

Matthew Johnson:

Drug_researcher, that's how to find me.

Andrew Huberman:

Great account by the way. Matthew and I have recently got into a dialogue there about some of the deeper effects of psychedelics in the literature versus how they're being discussed in the general public. And I follow his account and it's a really wonderful account for, whether or not you have a science background or not. If people are ... 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.

Matthew Johnson:

I'll try to get my Instagram game going on.

Andrew Huberman:

You're a busy guy. I get it. I'm running a lab too. I get it. You're busy. But drug_researcher there, as well.

Matthew Johnson:

Same handle.

Andrew Huberman:

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 explore clinical trials, participation in clinical trials of various kinds?

Matthew Johnson:

And so in our group, you go to hopkinspsychedelic.org, that's the website and if you can't remember that, just Johns Hopkins psychedelic.

Andrew Huberman:

Yeah, we will provide a link. We will provide a link.

Matthew Johnson:

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.

Andrew Huberman:

That means, he's being very polite. 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.

Matthew Johnson:

Right. And I try to get back to those emails. But frankly, it's because, I'm lucky the area has taken off so much, but there are many days where I simply get so many requests-

Andrew Huberman:

You have to do your research.

Matthew Johnson:

... that I can't get through my day if I answer all the ... Trust me, and something that a lot of folks don't get, and being in academia like we are, it's easy to forget how people understandably don't realize this: this is experimental research. It's FDA-approved as an experiment. 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 say, "I'm suffering from this complex constellation ... "

Andrew Huberman:

You're not a clinician.

Matthew Johnson:

... and depression and, yeah, I'm not a clinician. And even if I was, I wouldn't be able to treat them with psilocybin or to send them anywhere that was legal to take it. If we're going to be treating you, 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 treatment-resistant tobacco use disorder, so nicotine addiction. Very specific studies. This is not one-off treatment.

Matthew Johnson:

And folks say like, "Oh, I can pay to go out to Baltimore. Oh, my son has this complex," and they're tragic cases. If you're interested in a study, go to our website. If it's not on their website, we don't have a study on it. There are going to be forthcoming studies. So I'm going to be starting studies on opioid addiction and PTSD, and an LSD study for chronic pain. The day that those are open for recruitment, they're going to be up on our website. That's where you look to see everything. And in fact, I just recently, a couple days ago, put up a couple surveys, so it's also where we post links to our survey study.

Matthew Johnson:

If you've had psychedelics, and you've taken them for therapeutic intent for PTSD or for depression or anxiety, you can find a link. And also if you've done breathwork for those reasons, we have a link for a study of that type up there now which is a holotropic style, very psychedelic type of breathing technique that can lead to some of these similar experiences. So it's up there.

Matthew Johnson:

More broadly, outside of our group, because there's a growing number of groups in the U.S. doing this, and in Europe doing this research. But you can gov, and if you look in for 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 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 on clinicaltrials.gov. So check out clinicaltrials.gov to see what's going on. 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-off treatment.

Andrew Huberman:

Yeah. And I should say just, and not just legal, but also supported in the right framework that you described, of having a team, et cetera. Obviously people will do what they will do.

Matthew Johnson:

I will say if people ... I never encourage people to take drugs of any ... I don't encourage caffeine use. Every drug has its risk.

Andrew Huberman:

I encourage my own caffeine use, but nobody else's.

Matthew Johnson:

I'm drinking up right now. This is great.

Andrew Huberman:

Yeah, this is very strong maté, it's what we're drinking. It has not led to an alteration in my perception of self to the extent that we talked about earlier. However, this conversation was 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.

Matthew Johnson:

Thank you. Well, thanks for helping to spread that light, and 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.

Andrew Huberman:

Well, it's my pleasure. Thank you.

Andrew Huberman:

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 guests in the comment section on YouTube. As well, please consider subscribing on Apple and on Spotify, and on Apple you can leave us up to a five-star review and a comment. Please also check out the sponsors that we mentioned at the beginning of today's episode. That's a terrific way to support our podcast. And last but not least, thank you for your interest in science.

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