Matthew W. Johnson is a professor and psychedelics researcher at Johns Hopkins. Please support this podcast by checking out our sponsors:
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EPISODE LINKS:
Matt's Twitter: https://twitter.com/Drug_Researcher
Matt's Website: https://www.hopkinsmedicine.org/profiles/results/directory/profile/0800020/matthew-johnson
Study Website: https://hopkinspsychedelic.org/

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OUTLINE:
0:00 - Introduction
2:02 - Introduction to psychedelics
18:04 - Psychedelics expand the mind
21:16 - The priors we bring to the psychedelic experience
25:11 - Elon Musk and first principles thinking
35:41 - DMT
47:03 - Joe Rogan and DMT
53:11 - The nature of drug addiction
1:07:00 - The economics of drug pricing
1:13:15 - Should we legalize all drugs?
1:25:18 - What is the most dangerous drug?
1:27:52 - Does drug prohibition work?
1:31:46 - Cocaine and sex
1:38:46 - Risky sexual decisions
1:49:43 - Psilocybin helping people quit smoking
1:56:01 - Young Jamie
2:18:09 - Participating in a study
2:25:28 - Psychedelics and the human mind
2:32:51 - The future of psychedelics
2:35:32 - Neuralink
2:45:05 - Consciousness
2:57:46 - Panpsychism
3:07:51 - Aliens and DMT
3:17:55 - Mortality
3:27:44 - Meaning of life

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The following is a conversation with Matthew Johnson, a professor of psychiatry and behavioral science at Johns Hopkins, and is 1 of the top scientists in the world conducting seminal research on psychedelics.

This was 1 of the most eye-opening and fascinating conversations I've ever had on this podcast.

I'm sure I'll talk with Matt many more times.

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As a side note, let me say that psychedelics is an area of study that is fascinating to me, in that it gives hints that much of the magic of our experience arises from just a few chemical interactions in the brain, and that the nature of that experience can be expanded through the tools of biology, chemistry, physics, neuroscience, and artificial intelligence.

The fact that a world-class scientist and researcher like Matt can apply rigor to our study of this mysterious and fascinating topic is exciting to me beyond words, as is the case with any of my colleagues who dare to venture out into the darkness of all that is unknown about the human mind, with both an openness of first principle thinking and the rigor of the scientific method.

If you enjoy this thing, subscribe on YouTube, review it with 5 Stars on Apple Podcasts, follow on Spotify, support on Patreon, or connect with me on Twitter at Lex Friedman.

And now, here's my conversation with Matthew Johnson.

Can you give an introduction to psychedelics, like a whirlwind overview?

Maybe what are psychedelics and what are the kinds of psychedelics out there and in whatever way you find meaningful to categorize.

Yeah, you can categorize them by their chemical structure.

So phenethylamines, tryptamines, ergalines, that is less of a meaningful way to classify them.

I think that their pharmacological activity, their receptor activity is the best way.

Well, let me start even broader than that because there I'm talking about the classic psychedelics.

So broadly speaking, when we say psychedelic, that refers to, for most people, a broad number of compounds that work in different pharmacological ways.

So it includes the so-called classic psychedelics.

That includes psilocybin and psilocin, which are in mushrooms, LSD, dimethyltryptamine or DMT, it's in ayahuasca, people can smoke it too, mescaline, which is in peyote and San Pedro, cactus.

And those all work by hitting a certain subtype of serotonin receptor, the serotonin 2A receptor.

Other compounds like PCP, ketamine, MDMA, ibogaine, they all are more broadly speaking called psychedelics, but they work by very different ways pharmacologically.

And they have some different effects, including some subjective effects, even though there's enough of an overlap in the subjective effects That you know people informally refer to them as psychedelic and I think what that overlap is You know compared to say, you know caffeine and cocaine and you know ambien, etc other psychoactive drugs is that they have strong effects in altering one's sense of reality and including the sense of self.

And I should throw in there that cannabis, more historically like in the 70s, has been called a minor psychedelic.

And I think with that latter definition, it does fit that definition, particularly if 1 doesn't have a tolerance.

So you mentioned serotonin, so most of the effect comes from something around like the chemistry around neurotransmitters and so on.

So it's chemical interactions in the brain or is there other kinds of interactions that have this kind of perception and self-awareness altering effects?

Well, as far as we know, all of the psychedelics of all the different classes we've talked about, their major activity is caused by receptor level events.

So either acting at the post receptor side of the synapse, so in other words, neurotransmission operates by, you know, 1 neuron releasing neurotransmitter into a synapse, a gap between the 2 neurons, and then the other neuron receives.

They have, it has receptors that receives, and then there can be an activation caused by that.

So all of the major psychedelics work by either acting as a pitcher, mimicking a pitcher or a catcher.

So for example, the classic psychedelics, they fit into the same catcher's mitt on the post-receptor, post-synaptic receptor side as serotonin itself, But they do a slightly different thing to the cell, to the neuron than serotonin does.

There's a different signaling pathway after that initial activation.

Something like MDMA works at the presynaptic side, the pitcher side, and basically it floods the synapse or the gap between the cells with a bunch of serotonin, the natural neurotransmitter.

So it's like the pitcher in a baseball game all of a sudden just starts throwing balls like every second.

Everything we're talking about, is it often more natural, meaning found in the natural world?

Or is it chemically manufactured, like artificially in the lab?

So using terminology that's not chemical terminology, not like the terminology you see in titles of papers, academic papers, but more sort of common parlance.

Right, it would be good to kind of define their, you know, their effects, like how they're different.

And so it includes LSD, psilocybin, which is in mushrooms, mescaline, DMT.

So the 1 most people will know is peyote, but it also shows up in San Pedro or Peruvian torch.

And all of these classic psychedelics, they have at the right dose, you know, and typically they have very strong effects on one's sense of reality and one's sense of self.

What, some of the things that makes them different than other, more broadly speaking, psychedelics like MDMA and others is that they're, at least the major examples, there are some exotic ones that differ, but the ones I've talked about are extremely safe at the physiological level.

Like there's like LSD and psilocybin, there's no known lethal overdose, unless you have like really severe, you know, heart disease, you know, cause it modestly raises your blood pressure.

So same person that might be hurt, shoveling snow or going up the stairs, you know, that could have a cardiac event because they've taken 1 of these drugs.

But for most people, you know, someone could take a thousand times what the effective dose is and it's not gonna cause any organ damage, affect the brainstem, make them stop breathing.

So in that sense, you know, it's they're freakishly safe at the physio, I would never call any compound safe because there's always a risk.

They're freakishly safe at the physiological level.

I mean, you can hardly find anything over the counter like that, I mean, aspirin's not like that, caffeine is not like that.

Most drugs, you take 5, 10, 20, maybe it takes 100, but you get to some times the effect of dose and it's gonna kill you or cause some serious damage.

And so that's something that's remarkable about most of these classic psychedelics.

That's incredible, by the way, that you can go on a hell of a journey in the mind, like probably transformative, potentially in a deeply transformative way, and yet there's no dose that in most people would have a lethal effect.

There's this duality between the mind and the body.

It's like, it's the, okay, sorry if I bring him up way too much, but David Goggins is like, you know, the kind of things you go on on the long run, like the hell you might go through in your mind.

Your mind can take a lot and you can go through a lot with the mind and the body will just be its own thing.

You can go through hell, but after a good night's sleep, be back to normal and the body is always there.

So bringing it back to Goggins, it's like you can do that without even destroying your knee or whatever.

So the unfortunate thing about the running, which he uses running to test the mind.

So the aspect of running that is negative, in order to test the mind, you really have to push the body, like take the body through a journey.

I wish there was another way of doing that in the physical exercise space.

I think there are exercises that are easier on the body than others, but running sure is a hell of an effective way to do it.

And 1 of the ways that where it differs is that you're, unlike exercise, you're essentially, you know, most exercise, to really get to those intense levels, you really need to be persistent about it.

mean, it'll be intense if you're really out of shape just jogging for 5 minutes, but to really get to those intense levels, you need to have the dedication.

And so some of the other ways of altering subjective effects or states of consciousness take that type of dedication.

Psychedelics though, I mean, someone takes the right dose, they're strapped into the roller coaster.

And something interesting is gonna happen.

And I really like what you said about that distinction between the mind, or the contrast between the mind effects and the bodily, the body effects, because I think of this, I do research with all the drugs, you know, caffeine, alcohol, methamphetamine, cocaine, alcohol, legal, illegal.

Most of these drugs, thinking about say cocaine and methamphetamine, you can't give to a regular user, you can't safely give a dose where the regular cocaine user is going to say, oh man, that's the strongest coke I've ever had, because you get it past the ethics committee and you need approval.

And I wouldn't want to give someone something that's dangerous.

So to go to those levels where they would say that you would have to give something that's physiologically riskier.

You know, psilocybin or LSD, you can give a dose at the physiological level that is like very good chance it's gonna be the most intense psychological experience of that person's life.

And have 0 chance for most people, if you screen them, of killing them.

The big risk is behavioral toxicity, which is a fancy way of saying doing something stupid.

Like if you wander into traffic or you fall from a height, just like plenty of people do on high doses of alcohol.

And the other kind of unique thing about classic psychedelics is that they're not addictive, which is pretty much unheard of when it comes to so-called drugs of abuse or drugs that people at least at some frequency choose to take.

You know, most of what we think of as drugs, you know, even caffeine, alcohol, cocaine, cannabis.

Most of these you can get into alcohol, you can get into a daily use pattern.

And that's just extreme, so unheard of with psychedelics.

Most people have taken these things on a daily basis.

It's more like they're building up the courage to do it and then they build up a tolerance.

Or they're in college and they do it on a dare.

you have and say, oh God, I gotta stop taking this, I gotta stop drinking every night, I gotta cut down on the Coke, whatever.

What are the, what's a good term, modern psychedelics, or more maybe psychedelics that are created in the lab.

And I should say that with the classic psychedelics that LSD is sort of, you can call it a semi-synthetic because there's natural, you know, from both ergot and in certain seeds, morning glory seeds is 1 example.

There's a very close, there are some very close chemical relatives of LSD.

So LSD is close to what occurs in nature, but not quite.

But then when we get into the other non-classic psychedelics, probably the most prominent 1 is MDMA.

People call it ecstasy, people call it molly.

And it differs from classic psychedelics in a number of ways.

It's like, you can have cocaine on this end of the continuum, and classic psychedelics here.

Continuum of addiction, you know, so it's certainly no cocaine.

It's pretty rare for people to get into daily use patterns, but it's possible.

And they can get into more like, you know, using once a week pattern where they can find it hard to stop.

But it's somewhere in between, mostly towards the classic psychedelic side in terms of like relatively little addiction potential.

But it's also more physiologically dangerous.

I think that certainly the therapeutic use, it's showing really promising effects for treating PTSD and the models that are used, I think those are extremely acceptable when it comes to the risk-benefit ratio that you see all throughout medicine.

But nonetheless, we do know that at a certain dose and a certain frequency that MDMA can cause long-term damage to the serotonin system in the brain, so it doesn't have that level of kind of freakish bodily safety that the classic psychedelics do.

And it has more of a heart load, a cardiovascular, I don't mean kind of emotion, I mean, in this sense, although it is very emotional, and that's something unique about its subjective effects, but it's more of a presser.

And the terminology used instead of like a freakish capacity, allowing you from a researcher perspective, but a personal perspective too, of taking a journey with some of these psychedelics that is the heroic dose, as they say.

So like these are tools that allow you to take a serious mental journey, whatever that is.

And with MDMA, there's a little bit, it starts entering this territory where you gotta be careful about the risks to the body, potentially.

So, yes, that, in the sense that you can't kinda push the dose up as high, as safely as 1 can, if they're in the right setting, like in our research, as they can with the classic psychedelics.

But probably more importantly, just the nature of the effects with MDMA aren't the full-on psychedelic.

So it's sort of a psychedelic with rose-colored glasses on, a psychedelic that's more of it's been called more of a heart trip than a head trip.

The nature of reality doesn't unravel as frequently as it does with classic psychedelics.

But you're able to more directly sense your environment.

It's not completely detached from reality with MDMA.

That said, at most doses of classic psychedelics, you still have a tether to reality.

Changes a little bit when you're talking about smoking DMT or smoking 5-methoxy DMT, which are some interesting examples we could talk more about, but with MDMA, for example, it's very rare to have what's called an ego loss experience or a sense of transcendental unity where 1 really seemingly loses the psychological construct of the self.

But MDMA, it's very common for people to have this, they still are perceiving themselves as a self, but it's common for them to have this warmth, this empathy for humanity and for their friends and loved ones.

So it's more, and you see those effects under the classic psychedelics, but that's a subset of what the classic psychedelics do.

So I see MDMA in terms of its subjective effects, is if you think about Venn diagrams, it's sort of MDMA is all within the classic psychedelics.

everything that you see on a particular MDMA session, sometimes a psilocybin session looks just like that.

But then sometimes it's completely different with psilocybin.

It's a little more narrowed in terms of the variability with MDMA.

Is there something general to say about what the psychedelics do to the human mind?

You mentioned kind of an ego loss experience.

In the space of Venn diagrams, if we're to draw a big circle, what can we say about that big circle?

In terms of people's report of subjective experience, probably 1 of the most general things we can say is that it expands that range.

So many people come out of these sessions saying that they didn't know it was possible to have an experience like that.

So there's an emphasis on the subjective experience that is there words that people put to it that capture that experience, or is it something that just has to be experienced?

As a researcher, that's an interesting question because you have to kind of measure the effects of this.

And how do you convert that into numbers?

Is that possible To 1, convert it into words, and the second, convert the words into numbers somehow.

So we do a lot of that with questionnaires, you know, some of which are very psychometrically validated, so lots of numbers have been crunched on them.

And there's always a limitation with questionnaires.

I mean, subjective effects are subjective effects.

Ultimately, it's what the person is reporting, and that doesn't necessarily point towards a ground truth.

So, for example, if someone says that they felt like they touched another dimension or they felt like they sensed the reality of God or if they, you know, I mean just you name it, people's ontological views can sometimes shift.

I think that's more about where they're coming from.

And I don't think it's the quintessential way in which they work.

There's plenty of people that hold on to a completely naturalistic viewpoint and have profound and helpful experiences with these compounds.

But the subjective effects can be so broad that for some people it shifts their philosophical viewpoint more towards idealism, more towards thinking of the nature of reality might be more about consciousness than about material.

Right now we have essentially 0 to say about that in terms of validating those types of claims, but it's even interesting just to see what people say along those lines.

So you're interested in saying like, can we more rigorously study this process of expansion?

Like, what do we mean by this expansion of your sense of what is possible in the experiences in this world?

Right, as much as what we can say about that through naturalistic psychology.

Especially as much as we can root it to solid psychological constructs and solid neuroscientific constructs.

And I wonder what the impact is of the language that you bring to the table.

So you mentioned about God or, speaking of God, a lot of people are really interested in theoretical physics these days at a very surface level.

And You can bring the language of physics, right?

You can talk about quantum mechanics, you can talk about general relativity and curvature of space-time, and using just that language without a deep technical understanding of it to somehow start thinking like, sort of visualizing atoms in your head and somehow through that process, because you have the language, using that language to kind of dissolve the ego, like realize that we're just all little bits of physical objects that behave in mysterious ways.

Like if you read a Sean Carroll book or something recently, it seems like it has a huge influence on the way you might experience, might perceive the world and might experience the alteration that psychedelics brings to your perception system.

So I wonder, like, the language you bring to the table, how that affects the journey you go on with the psychedelics.

And I think there's, I'm a little concerned some of the science is going a little too far in the direction of, of around the edges, you know, speaking about it, changing beliefs in this sense or that sense about particular in particular domains.

And I think what really what, a lot of what's going on is what you just discussed.

So if you've been reading a lot of, you know, physics, then you might, you know, bring up, you know, like, you know, space time and interpret the experience in that sense.

I mean, it's not uncommon for people come out talking about visions of the—it's not the most typical thing, but it's come up in sessions I've guided—the Big Bang and this sort of nature of reality.

I think probably the best way to think about these experiences is that, and the best evidence even though we're in our infancy and understanding it, that They really tap into more general psychological mechanisms.

I think 1 of the best arguments is they reduce the influence of our priors, of what we bring into all of the assumptions that we all, you know, we're essentially, especially as adults, we're riding on top of heuristic after heuristic to get through life.

And you need to do that, and that's a good thing, and that's extremely efficient, and evolution has shaped that.

But that comes at an expense, And it seems that these experiences will allow someone greater mental flexibility and openness.

And so 1 can be both less influenced by their prior assumptions, but still nonetheless, the nature of the experience can be influenced by what they've been exposed to in the world.

And sometimes they can get it in a deeper way.

Like maybe they've read, I mean, I had a philosophy professor 1 time as a participant in a high-dose psilocybin study, and I remember him saying, my God, it's like Hegel's opposites defining each other.

I've taught this thing for years and years and years.

And so, like that, you know, and even at the psychological, emotional level, like the cancer patients we worked with, you know, they told themselves a million times over the people trying to quit smoking, I need to quit smoking.

Oh, I'm ruining my life with this cancer.

I'm still healthy, I should be getting out, I'm letting this thing defeat me.

It's like, yeah, you told yourself that in your head, but sometimes they have these experiences and they kind of feel it in their heart.

So in some sense that you bring some prize to the table, but psychedelics allow you to acknowledge them and then throw them away.

So like 1 popular terminology around this in the engineering space is first principles thinking that Elon Musk, for example, espouses a lot.

Let me ask a fun question before we return to a more serious discussion.

With Elon Musk as an example, but it could be just engineers in general, Do you think there's a use for psychedelics to take a journey of rigorous first principles thinking?

So like throwing away, we're not talking about throwing away assumptions about the nature of reality in terms of like our philosophy of the way we live day-to-day life, but we're talking about how to build a better rocket, or how to build a better car, or how to build a better social network, or all those kinds of things, engineering questions.

I absolutely think there's huge potential there.

And there was some research in the late 60s, early 70s, that it was very early and not very rigorous in terms of methodology, but It was consistent with the, I mean, there's just countless anecdotes of folks.

I mean, people have argued that just, you know, Silicon Valley was largely influenced by psychedelic experience.

I remember the, I think the person that came up with the concept of freeware or shareware, it's like it kind of was generated you know, out of or influenced by psychedelic experience.

You know, so to this, I think there's incredible potential there and we know really next, there's no rigorous research on that but.

Is there anecdotal stuff like with Steve Jobs?

In your exploration of that, is there something a little bit more than just stories?

Is there like a little bit more of a solid data points, even if they're just experiential like anecdotes, is there something that you draw inspiration from like in your intuition?

Because we'll talk about you're trying to construct studies that are more rigorous around these questions.

But is there something you draw inspiration from from the past, from the 80s and the 90s and Silicon Valley, that kind of space?

Or is it just like, you have a sense based on everything you've learned and these kind of loose stories that there's something worth digging at?

I am influenced by the, gosh, the just incredible number of anecdotes surrounding these.

I mean, absolutely revolutionized biological sciences.

He says he wouldn't have won the Nobel Prize for it, said he wouldn't have come up with that had he not had psychedelic experiences.

You know, now he's an interesting character.

People should read his autobiography because you could point to other things he was into.

But I think that speaks to the casting your nets wide and this mental flex, more of these general mechanisms where sometimes if you cast your nets really wide, and it's going to depend on the person and their influences, but sometimes you come up with false positives.

You connect the dots where maybe you shouldn't have connected those dots, but I think that can be constrained, and so much of our, not only our personal psychological suffering, but our limitations, academically and in terms of technology, are because of the self-imposed limitations and heuristics, these entrenched ways of thinking, like those examples throughout the history of science where someone has come up with a rat, the paradigm, Kuhn's paradigm shifts.

It's like, here's something completely different.

This doesn't make sense by any of the previous models.

And then you need the right balance between that because so many of the novel crazy ideas are just bunk.

And that's what science is about, separating them from the valid paradigm shifting ideas.

But we need more paradigm shifting ideas in a big way.

And I think you could argue that we've, because of the structure of academia and science in modern times, it heavily biases against those.

Right, there's all kinds of mechanisms in our human nature that resist paradigm shift, quite sort of obviously.

So, and psychedelics, there could be a lot of other tools, but it seems like psychedelics could be 1 set of tools that encourage paradigm shifting thinking.

So like the first principles kind of thinking.

So it's a kind of, you're at the forefront of research here.

There's just kind of anecdotal stories, there's early studies, There's a sense that we don't understand very much, but there's a lot of depth here.

How do we get from there to where Elon and I can regularly, like I wake up every morning, I have deep work sessions where it's well understood like what dose to take, like if I want to explore something where it's all legal, where it's all understood and safe, all that kind of stuff.

How do we get from where we are today to there?

Not speaking in terms of legality in the sense like policymaking, all that like laws and stuff.

Meaning like how do we scientifically understand this stuff well enough to get to a place where I can just take it safely in order to expand my thinking, like this kind of first principles thinking, which I'm in my personal life currently doing, like How do I revolutionize particular several things?

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Matthew Johnson: Psychedelics | Lex Fridman Podcast #145