Dr. Matthew Johnson: Psychedelics for Treating Mental Disorders

- Welcome to the Huberman Lab Podcast,

where we discuss science

and science-based tools for everyday life.

[upbeat rock music]

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 Psychedelic 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.

Dr. Johnson and his work

have also been featured prominently in the popular press,

such as articles in "The New York Times"

and Michael Pollan's book, "How to Change Your Mind,"

and in a feature in "60 Minutes" about psychedelics

and the new emerging science of psychedelic therapies

for treating mental disorders.

During the course of today's conversation,

Dr. Johnson and I talk about psychedelics

at the level of what's called micro dosing,

whether or not it is useful

for the treatment of any mental disorders.

We also talk about more typical macrodosing,

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.

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And now, my conversation with Dr. Matthew Johnson.

Well, Matthew, I've been looking forward to this

for a long time.

I'm a huge fan of your scientific work,

and I'm here to learn from you.

So- - Likewise.

Big fan and happy to do this with you.

- 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?

- 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...

So 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 have 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.

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 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.

Mescalin, 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's the tryptamine-based compounds,

like psilocybin and DMT,

and then there's the phenethylamine-based compounds.

So these are the basic,

two of the, basically, building blocks

that you're starting from,

either a tryptamine structure or a phenethylamine structure.

But that's just the chemistry.

All of the...

What's more important,

or at least to someone like me,

are the receptor effects,

and then, ultimately, that's going to have a relationship

to the behavioral and subjective effects.

So all of these classic psychedelics

serve as agonist, or partial agonists,

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 Robo-tripping,

guzzling cough syrup,

which is something kind of like

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.

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- - Where does that come from?

- Salvia divinorum, it's a plant that became...

20 years ago, it sort of popped onto the legal high scene,

and there's a long history of this predating the internet,

going back to like the stuff one could order

in the back of "High Times Magazine",

and most of this stuff never worked, you know?

[laughs] 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.

So often...

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- - What does that mean?

- It means like touching within.

It sort of 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.

And 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.

And so structurally,

that's also in the phenethylamine class,

which contains mescalin, 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 post-synaptic 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- - Dumping

more serotonin. - Dumping more

serotonin. - Yeah.

- Flooding the synapse. - Yeah.

So I get the impression,

that this psychedelic space

is a enormous cloud of partially overlapping compounds.

- [Dr. Matthew] Right.

- Meaning some are impacting the serotonin system

more than the dopamine system.

Others are impacting the dopamine system

more than the serotonin system.

Given that the definition of a psychedelic

is that it profoundly alters sense of self,

at least that's included as a partial definition,

- Mm-hmm.

- can we break that down into a couple of sub categories?

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 - Yeah.

- that take psychedelics in sufficiently high doses.

So hallucinating, synesthesia.

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. - Right.

- And as a vision scientist,

the simplest explanation,

is when I move my hand

from one location to another location,

it's measuring the space,

the location of my hand in space over time,

and then you get a rate, and a speed,

and all that kind of stuff,

right? - Yeah.

- That gets more 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?

- I think it's fair to explore that area,

and here's what I'm thinking.

Clearly, there is a changed relationship,

certainly, at the right dose of orientation in space-time.

I think as a...

You know, I'm primarily a behaviorist,

and in terms of human behavioral pharmacology,

I always go to comparative pharmacology, okay?

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. - And the proprioception,

your balance, your vestibular. - Proprioception,

- Yeah. - you know.

And in many ways,

and sort of 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 that's something,

that there's something fundamental

about changing the representation in time and space.

There might be something to that.

I mean, I think of these psychedelics

as profoundly altering models.

We're prediction machines.

So much of that is top-down.

And psychedelics have a good way of,

loosely speaking, dissolving those models,

and one of, the reality- - Can you give us

an example of one of, like a model?

Like, 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

- Yes. - between objects and gravity.

But one of the first things that a child learns

is the relationship between objects, and gravity,

and their trajectory- - Yeah.

And with a four-year-old,

I mean, I saw that at earlier ages,

like that experimentation of, like,

oh yeah, that's what happens,

you know? - Right.

[interposing voices]

So if he were to throw a ball,

if a child were to throw a ball,

and it went up into the sky,

that would be absolutely mind-blowing?

- Yeah. - It would be

for an adult too.

- It'd be a pretty - Right.

- psychedelic experience,

probably [laughs]. - Right, right.

There's a rule there.

You're saying, there's kind of

a prediction. - Right.

- There's a rule that underlies a prediction,

that when that rule is violated,

all of a sudden, the circuit,

presumably, for that prediction,

it doesn't have a mind of its own,

but somehow, it creates a surprise element,

or a recognition element. - Yeah.

And it's not filtered out, you know?

And this might sound extreme,

but there are these cases,

it was overblown,

and sort of the propaganda of the late '60s, early '70s,

but there are credible cases of people,

it's very atypical of,

it 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, you know?

- Sure.

- They fall and die out of,

you know, from height, because they're drunk, you know?

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 [laughs]...

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? - All right, so-

So she was- - Into the other dimension-

- 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,

right? - Yeah.

- 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, - Yeah.

- in a general sense. - Mm-hmm.

- So compounds like LSD,

lysergic acid diethylamide and psilocybin,

my understanding, is that they primarily

target the serotonin system.

How do they do that at a kind of 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? - Yeah.

- I mean, at the end of the day, it's a chemical,

and these receptors are scattered around the brain

with billions of other receptors.

- [Dr. Matthew] Yeah.

- What do we think is going on in a general sense?

- Yeah, yeah, and this is really

the area of active exploration,

and we don't have great answers.

We know a good amount about the receptor level pharmacology,

some things about post-receptor signaling pathways.

In other words, just fitting into the receptor.

Clearly, serotonin itself is not psychedelic, you know?

Or else we'd be tripping, all of us,

all the time. - 'Cause when I eat a bagel,

I get serotonin release, right?

- Uh-huh. - I mean, there's...

Or turkey. - And it's very

different than LSD. - I mean, there's tryptophan

in it, right? - Mm-hmm.

- But my understanding of serotonin,

is that in very broad strokes,

that it generally leads to a state of being fairly,

it pushes the mind and body towards a state of contentment

within the - Right.

- immediate experience.

Whereas the dopamine system

really places us into an external view

of what's out there in the world, and what's possible.

- Yeah.

- Is that fair to say? - Need to do something.

I mean, that's consistent with my understanding,

and certainly, not in terms of...

I don't primarily identify as a neuroscientist,

so I'll 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.

- Well, feel free to explain it at the experiential level.

- Yeah. - 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 five neurons

and cortex? - Yeah.

- That conversation, we could hold,

and that's an interesting conversation.

But just in terms of the experience of serotonergic

versus dopaminergic drugs, - Right.

Yeah.

- they do seem to create distinct classes of experience.

So I think that's

the appropriate level - Right.

- for us to discuss them.

- And in terms of how they...

And I'd like to explore the biology a little bit here,

and tell you sort of what's known,

and what some of the ideas are.

- [Dr. Huberman] Please.

- You know, 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 a question best addressed by the biology,

the chemistry, or the physics?

That's how I think of receptor level,

post-receptor signaling,

downstream effects on other neuro-transmitters,

and then activation level effects,

and then coordination of activation.

So you've got the,

clearly, with the classic psychedelics,

the two way 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- - Do people

hallucinate on ketamine?

- Yes, yes, and it's more dissociative.

So someone is more likely to sort of

be less behaviorally active.

If they have a really high dose,

they go into a K-hole,

and if they go in a really high dose,

like you get in surgery, - That's what it's called,

- you're just unconscious. - a K-hole?

- Yeah, a K-hole. - Not an A-hole,

but a K-hole? - A K-hole,

yeah [laughs]. - Right.

- It's very different.

The K-hole.

And ketamine's interesting,

'cause people can take kind of bumps,

and kind of dance on it

with sort of an alcohol level strength effect,

and that's sort of the classic kind of raving use of it.

But then those folks want to titrate their dose,

because if they do more of a line,

you get up to like 75, 100 milligrams,

then you're talkin' about,

if you're on the dance floor, you're on the floor,

and your friends are trying to make sure

people aren't steppin' on you.

So that's like the K-hole- - Yeah, why would somebody

want to take a dissociative anesthetic?

Like, to me, it's completely mysterious

as to why someone would want to dissociate from their body.

- People claim that these NMDA antagonist psychedelics

are extremely insightful in a very similar way

to the experiences with the classic psychedelics.

So- - And ketamine is now legal

for therapeutic use, correct? - Right, right.

Spravato, the intra-nasal form marketed by Janssen,

which is esketamine,

and it's one of the- - It's prescription?

- Yeah, it's prescription-

and- - So people are taking

it in the nasal spray?

- Yeah. - And then,

are they undergoing talk therapy while they're doing this?

- Typically not.

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 Spravato,

the model is- - Spravato is?

- Is esketamine. - Okay.

- It's the, yeah, the spray form of ketamine.

It's been FDA-approved for treatment resistant depression.

You'll probably feel different.

Ignore that.

That's a side effect.

[laughs] 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 sort of 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, Spravato, 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.

You know, treating it as if it was a psychedelic therapy.

In other words, telling people,

you're going to have this experience.

It's going to...

We're hoping you learn something from it.

We're going to help you through it.

We're going to discuss it afterwards.

And they found incredibly high rates of success

in some pretty well controlled trials

for both heroin addiction and alcohol addiction.

So I think a whole lot of work needs to be done now.

And you see some of the ketamine clinics

that are using ketamine off-label,

a lot of them are you treating it like psychedelic therapy.

There's, essentially, no research at this point on that.

Do you get better results?

Straight up use of Spravato,

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,

you know? - Right.

- 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- - What would that look like?

- Really, just like our psilocybin sessions,

which I know I haven't described,

but briefly, you have anywhere from

four to eight hours of preparation

getting to know the people who are going to be the guides

or the therapists in the room

with the person. - Yeah, maybe you could

walk us through this?

So let's say, I were to come to one of your clinical trials,

'cause these are

clinical trials, right? - Mm-hmm.

- At your lab at Hopkins? - Yeah.

- And would I need to be depressed,

or could I just be somebody

who wanted to explore psychedelics?

- We've had studies for all of these,

- Okay. - and a number

of other disorders. - Okay.

- So healthy, "normal studies",

- Okay. - the code for

not a problem to fix, but we're all...

That's what's amazing about psychedelics, though,

because if you administer them under this model,

and you develop a relationship,

and give a high dose of a 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. - Sure.

Yeah- - But we've done

work with smoking cessation,

so people trying to quit tobacco,

and haven't been successful. - So a variety of reasons?

- Right. - So maybe,

I'll just ask some very simple questions

that would kind of step us through the process.

So let's say I were to sign up for one of these trials,

and I qualified for one of these trials.

I'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"?

- First, there's screening.

So it's kind of like a couple of days of both psychiatric,

like structured psychiatric interviews

about your whole, your past,

and symptoms across the DSM, the psychiatric Bible,

to see if you might have various disorders

that could disqualify you,

like the main ones being the psychotic disorders,

schizophrenia, and also including bipolar.

- Right. - So the manic

side of bipolar. - Mm-hmm.

- So after that...

And also cardiovascular screening, heart disease.

After that screening, then the preparation.

You develop a therapeutic rapport

with the people who are going to be

in the room with you, your guides,

but you're also then didactically sort of explained

about what the psychedelic could be like,

and that's kind of a laundry list,

because they're more known by their variability

than it's going to...

It's not like cocaine.

You're going to feel stimulated.

You're going to feel like you can do any...

Or alcohol, you're probably going to feel more relaxed.

It's like...

I call 'em uppers, downers, and all arounders,

and the psychedelics are the all arounders.

It's like, yeah, you could be,

you could have the most

beautiful experience of your life,

or the most terrifying experience of your life.

So it's this kind of laundry list

of like the things that could happen,

so there's no surprises.

- I think it's so important for people to hear,

because the all arounders,

you really can't predict how somebody

is going to react internally.

- Right.

- 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 recalled to mind,

that how most prescription antidepressants work

is also very mysterious.

They increase serotonin, or dopamine,

or epinephrin, et cetera,

but why they take weeks on end,

you know, 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. - Yeah.

- Comes the day that they are

going to have this experience.

Are they eating mushrooms,

like you hear about,

or are they taking it in capsule form?

What sorts of doses are you prescribing?

Is there a dose response curve?

- [Dr. Matthew] Yeah.

- And then secondary to that,

I'd like to talk about micro dose

versus macro dose. - Mm-hmm.

- So how do they get this stuff into...

How do people receive it,

and how do they get it

into their body? - So they reive

pure psilocybin.

So the mushroom, and there are many species...

People have taken mushrooms in the United States,

it's most likely so Psilocybe cubensis.

They're easy to grow.

They grow in cow patties.

It's easy for anybody to grow 'em in their closet.

It doesn't take a 1,000 watt light, like cannabis.

It takes like a little 10 watt light bulb

and a Tupperware bin.

So those are what...

Those are the types of mushrooms that people typically take.

We're not administering those.

Psilocybin is the compound.

You could draw a molecule of psilocybin,

again, based on the tryptamine structure,

that's a single molecular entity.

So it's a white powder.

- Does it look like serotonin molecularly?

- Yes, yes, yes.

[interposing voices]

- If I were to show people

the chemical structure of serotonin

and the chemical structure of psilocybin,

it would look quite similar?

- Right, right.

[interposing voices] - They're basically

taking serotonin?

- A modified version of serotonin, which makes sense.

But then again, this repeated theme of

the chemistry doesn't always neatly line up,

because mescaline looks more like dopamine

than it does like serotonin,

but yet, at the receptor activation level,

the pharmalogical effect, those are similar.

But yeah, I mean, and what it does at the receptor is an...

It's hitting the same switch,

but then having an alternate response

at the receptor level. - Yeah, 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 a psilocybin might trigger activation

of different components of that pathway, different rates,

and so you can get vastly different experiences

from two things that look chemically similar.

- Right. - This is also

a good reason why people shouldn't just assume

that they can cowboy their own chemistry, right?

That what you see on paper

and what you can mix up in a vile

is often vastly different than what you predict.

- Right. - Right.

- And there's a dose effect curve that's really interesting.

Some of our early work with psilocybin in healthy "normals"

looked at a true placebo, plus four active doses,

5, 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

where we're dropping the body weight adjustment,

'cause going across hundreds of volunteers,

we've kind of figured out,

that you shouldn't really be,

you don't need to be adjusting

by body weight, so- - Interesting.

- So yeah.

- Well, brain size doesn't vary

that much between individuals.

- Yeah, yeah.

- You know, at the end, this is a brain effect,

mostly. - Yeah.

- Probably body as well.

Okay, so the person ingests the powder

or capsule? - Yeah, in a little pill.

- Okay. - Yeah.

And it doesn't take- - And how long does it-

- 30 milligrams is a small...

He could fit it into a tiny, little capsule.

And it'll take about a half hour.

Well, anywhere from 15 minutes to an hour to kick in.

On average, about a- - And you said,

the dose range was?

- Most of our studies are looking at where

we want a psychedelic effect

during 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 is not full of,

for most of our studies, is not full of tasks.

We really want to look at the therapeutic response.

Obviously, if it's a therapeutic study,

we want it to be a meaningful experience.

And research has found, not surprisingly,

that you get a less meaningful experience

when you're an FMRI,

- Right. - ar when you're doing

a lot of cognitive tasks.

We've done some research on 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.

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,

is to have that preparation,

so you the person feels very comfortable with their guides.

I mean, ultimately, what I tell people is like,

any emotional response, it's all welcome.

I mean, you could be crying like a baby hysterically,

like that's what you should be doing

if that's what you feel like.

And so in a lot of ways,

sometimes people with psychedelic experience on their own,

it can be harder to train them in this model,

because in the real world,

people with psychedelic experience,

a lot of times, the rule is hold your shit.

So 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,

like crying about your mother.

Your other friends,

they're having an experience too,

and you're being a drama king, and blah-blah-blah,

And so, yeah, compose yourself.

Hold your- - You're doing-

I mean, you're doing therapy for people.

It's not just about the experience?

- 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.

Once you let go of control,

right? - 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 sort of generic case example, if you will.

The letting go of control

is an interesting feature, actually,

because one of the common themes of good psychoanalysis,

or psychotherapy of any kind,

is that there's a trust built

between the patient and the analyst,

and that relationship becomes

a template for trust more generally,

and trust in one's self.

It's actually, the end goal of a good psychoanalysis

is that the patient actually...

One of the end goals

is that they develop an empathy for themselves,

which almost sounds like an oxymoron,

but if you spend a little time with that statement,

it actually pans out.

So the psychedelic experience is one in which,

chemically, you're under a new set of conditions, right?

- Yeah. - Let's coarsely,

space and time are altered in some way, sense of self.

For instance, I might be going to

a strongly interoceptive mode

where I'm focusing on

everything within the confines of my skin.

Whereas, normally, we're sort of interacting in space,

and pens, and conversation.

[mumbles] Occasionally, I'll pay attention to my breathing,

but I'm sort of dilating

and contracting my focus for

different things all the time. - Yeah.

- 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.

- [Dr. Matthew] Yeah.

You're not worried whether

or not your brain is going to explode,

even though a thought could feel enormous.

If I keep going like this,

it almost sounds 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- - Especially these days.

Yeah, multi-task. - Exactly.

Yeah. - Right.

Multitask.

And the more that we focus on one thing,

the more bizarre that thing

actually can appear to us, right?

- Right. - I mean,

even if it's the tip of your finger,

and you're not taking any psychedelics,

you spend long enough looking at the tip of your finger,

you will notice

- Yeah, it's weird. - some very

weird things. - Yeah.

- Right?

- I think if that as the classic psychedelic effect,

or one classic effect,

and one I've used many times,

of this example of why people should necessarily...

These aren't...

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 realize, like that's,

their hand is the most amazing miracle.

Like the entire universe has essentially conspired

to come to this one point

to make this absolutely breathtaking...

It's almost like, I think, of the simplest form of...

Well, we know that 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 disc

habituation component that- - Disc habituation?

- Yeah, so like we wouldn't - Yeah.

- be able to get through life,

we wouldn't be able to cross that street if we were like,

whoa, this is a miracle.

You know? [laughs] - Well, I'm so glad you-

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,

but 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.

- Right. - But most of us

don't look at any one thing for very long.

- [Dr. Matthew] Right.

- The brain's default is to

perceptually jump around like crazy

with the visual system, with the auditory system.

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, - Yeah.

- is the safety...

It's sort of like a permission to do that

without worrying that something's going to happen.

- 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...

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- - Are you monitoring

this the whole time? - We do.

We do monitor it. - So they're plugged into

a variety of devices- - Yeah,

so every half hour or so,

we take 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.

- [Dr. Huberman] Sure.

- But yeah, 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.

This sort of...

And the breath is obviously interesting,

because it's this automatic control,

but it can also be voluntary.

So people get into a sense of like,

my god, what if I...

It sounds silly,

like a stoner movie- - What if I forget to breathe?

- Exactly. - Yeah.

- That can be so compelling.

And so one of the...

Get back to one of your questions,

it's like, what do we do to kind of

allow them to go further into these bubbles?

One, is wearing the eye shades.

We don't call 'em blindfolds,

'cause that has a negative connotation,

like peakin' out [laughs]. - And they're probably seeing

a lot in there anyway.

So blind isn't the appropriate

word for it. - Right, right.

I've never thought of it.

This should be like inner-sight shades.

[interposing voices]

- But when you close the eyes,

the levels of activity in the retina

actually are maintained.

It's just spontaneous activity.

- And it seems,

and I'd be curious about your thoughts on this, I mean,

but the way I describe it,

is that the mind's eye,

this kind of loose term we use,

can be on rocket booster.

So a lot of times, for some people,

like a compound like psilocybin,

for some people, there's no perceptual effect.

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..."

On these compounds,

people don't typically see pink elephants.

You do actually get that in another class.

I didn't mention the anticholinergic,

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.

- Right. [interposing voices]

We will definitely get to those.

But the reason I kind of cringe,

and I 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 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. - Yeah.

- And there's a lot of mythology around the broomsticks.

It's complicated.

But that sounds very unpleasant.

One thing about the serotonergic,

let's just, for with psilocybin,

so there's an expansion of a particular,

fairly narrow, percept.

It could be sound.

- Yeah. - It could be an emotion.

It could be sadness.

Could be a historical event,

or a fear of the future. - Yes.

- And you've mentioned before,

that there's something to be learned in that experience.

- [Dr. Matthew] Yeah.

- There's something about going into that experience

in an undeterred way

that allows somebody to bring something back

into more standard reality.

- Yeah.

- Given the huge variety of experiences

that people have on psychedelics,

given the huge variety of humans that are out there,

but what are now very clear

therapeutic effects in the realm of depression,

what do you think is the value of going into this

fairly restricted perceptual bubble,

what we are calling, letting go, 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, - Yeah.

- that raises all sorts of interesting questions.

And this is not a philosophy discussion.

We're talking about biology

and psychology here. - Yeah.

So let's say, I decide that 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 Pilots V5s

[Dr. Matthew laughs] and V7s very much.

But I could feel real love

- Yeah. - for the pen,

right? - Yeah.

- That's not an unreasonable thing to expect

in a psychedelic journey.

- Right, right. - And in the context

of your laboratory model,

which I think is a great one,

that experience will 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.

- Yeah. - And yet,

the export from that,

those two vastly different experiences,

is one of feeling a better relationship to the world

into one's self. - Right.

- So what does this

tell us about- - How can the pen,

- Right. - and the processing

your childhood trauma

both lead to- - Right.

- Yeah- - So what does this...

I mean, at that level, - Yeah.

- it raises this question, like,

first of all, how, why,

I mean, or just, what are your thoughts on that?

- So this is definitely in the...

This is in the terrain we're figuring out, you know?

So there's no...

Educated speculation is the best I can provide.

but I think the best...

I think the common denominator are persisting changes

and self-representation.

- Okay, tell me more about self-representation.

Yeah. - That's the way

one holds the sense of self,

the fundamental relationship of a person in the world.

I mentioned earlier, that these experience

seems to alter the models we hold of reality,

and I think the self is the biggest model,

that I am a thing that's separate from other things.

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 endpoint 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 the whole idea that you could

have such a deep connection with this random,

obviously, random, aspect of the universe

could potentially lead to this

transformed understanding of the self,

and the pen may be a proxy for the miracle of reality

in a way that relies nothing on,

on no supernatural thinking.

You know, you can be a hard atheist, and you take this,

you know, 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 used the pen,

but I think it sounds similar to

Aldous Huxley's classic description

and the doors of perception of the chair and the drapes.

He took 500 milligrams of mescalin,

and he was just like- - Is that a

high dose of mescalin? - Yeah, yeah,

and that's a heroic dose, for sure.

He's just going off of the chairiness of the chair,

like this chair is exuding the quality of being a chair,

and- - So this is this

expansion of the perceptual bubble?

A narrow percept that then grows within

the confines of that narrow percept?

- Yeah.

- So a 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.

This process, we call interoception.

And then there's the the title of the self,

the I am blank.

- Yeah. - And I noticed

you said that several times,

and it's intriguing to me.

But a good friend,

I don't think I can or should mention his name,

but he had a very long and successful career

within one of the more elite teams 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.

The first pass,

it sounded to me a little bit like, you know,

kind of like internet psychology-type-thing,

like, oh, the secret or something you'd say,

which frankly,

I'm just not particularly- - A little New Agey.

- Yeah. - Yeah.

- [mumbles] If you kind of like

the whole fake it till you make it,

I don't actually subscribe to any of that.

- [Dr. Matthew] Uh-huh.

- 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 reprogram 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,

- Yeah. - allows us

to potentially reshape the perception of self,

that's a tremendous feat of neuroplasticity.

- Right.

And I think, certainly, more work needs to be done.

This is the horizon.

And I actually 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".

- That's the title of the book?

- It might be "Psychedelic Philosophy"?

- Okay. - It's really-

- Chris Letheby.

We'll put a link to it- - Right.

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 like,

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.

I mean, there's this real...

There seems to be, when it really works,

this change in how people view themselves,

like with smoking,

like really stepping out of this model of like,

I'm a smoker, it's tough to quit smoking cigarettes.

I can't do it.

I failed a bunch of times.

I remember one participant during the session,

but he held onto this afterward, said,

"My god, it's like I can really just decide,

like flicking off a button,

I can decide not to smoke".

I call these duh experiences with psychedelics,

'cause people often, like in the cancer stage, 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...

So it sounds...

When it comes out of their mouths,

folks will say,

this is part of the ineffability

of a psychedelic experience,

folks say, "I know this sounds like bullshit

and this sounds like,

but my god, I could just sigh",

like they're feeling this gravity of agency,

which I think is interesting,

cause regardless of the debates on the reality of freewill,

I think the philosophy of that,

whether it's ultimately free will,

like pure agency, if that exists,

which I'm skeptical of,

or just the idea, that clearly, we have a sense of agency.

There's something there,

whether it's the sense of agency even,

the human being has,

and that seems to be, at times,

fundamentally, supercharged from a psychedelic experience.

This idea like, I'm just going to make a decision.

Like normally, like you tell a depressed person,

don't think of yourself that way.

You're not a failure.

- They can't do it. [interposing voices]

- It's just, yeah.

It's like- - Right.

- Well- - But you can, actually,

in one of these states,

have an experience where you realize, like, my god.

Just like 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 that...

You know, reconsolidation of those memories,

they are altered,

very consistent with our understanding

of the way memory works.

So the whole idea, people can actually,

in a few hours, have a such a profound experience

that they decide to make these changes

in who they are, and it sticks,

there seems to be something like that.

- And that's profound.

I mean, I think, a few moments ago,

I made a some semi-disparaging statements

about things like the secret, and affirmations,

and the reason I do that

with a nod to the fact that the people

who are putting those ideas forward

are well-intentioned people,

is that the neural networks of the brain put language last.

We tell stories, you know?

And stories are very powerful.

But I think one of the most cruel aspects

of the whole self-help literature in 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.

Is it very hard to control thoughts?

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 it",

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.

- [Dr. Matthew] Yeah.

- And just fundamentally,

there are some prerequisites.

You need certain neuromodulators present,

like serotonin or dopamine.

You need them to be at sufficient levels.

You don't need a drug necessarily to do it.

You 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?

- Yeah. - Likewise with an adult

in certain circumstances.

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,

- Yeah. - is what allows us

to reshape our neural circuitry,

and to feel differently about ourselves.

And I know there's been really tremendous success

in many individuals of alleviating depression,

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?

And I want to talk about the transition out of that state,

and then the export into life,

because this is really where the

power of psychedelic seems to be

in the therapeutic sense,

is the ability to learn, truly learn, from that experience,

so that the learning becomes the default.

That one doesn't have to remind themselves,

oh, I am...

You know, they don't have to do an affirmation,

I am a happy person, I am a...

You know, I always think of

Bart Simpson - Right

- writing on the chalkboard. [Dr. Matthew laughs]

- Yeah. - It didn't work for him

It doesn't work for this other stuff too.

So as they transition out of this state,

I know that there's a kind of a heightened,

there's a so-called peak,

- Yeah. - 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.

- Right. - 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. - Right.

- What do you do to guide people through the,

out the tunnel,

as they exit the tunnel? - Yeah.

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.

[interposing voices]

- In your studies,

are they writing or talking

as they're doing it? - So-

And it's called a very loosey goosey term, integration,

but for us means,

as they're coming back from the experience,

so sort of five, six hours in,

so this is the afternoon,

they've been dosed around nine o'clock,

so this is like four o'clock or so,

just some initial, tell us about the experience.

Do you want to...

Not unpacking it totally,

but just kind of initially

just have a little bit of 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 one to two hour,

depending on the study, "integration session",

basically, let's discuss your experience.

And depending on what study it's in,

like what that mean for...

You're dealing with cancer,

what might that mean for your smoking,

or becoming a non smoker?

So you encourage them to simply take it seriously.

And I think this is, again, a sort of,

one of the points that could be the antithesis

of what some just kind of social users use.

I mean, this was written about by 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 are like,

ah, dude, you were screwed up!

Too much acid for you!

Whoo!

You know?

Like, man, next time, you needed to have a few more beers

to bring that down.

You know, like 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 like, tell me more about that.

You know, you were crying at one point

in talking about your mom.

Let's talk about that.

What was that like?

Do you remember that?

[interposing voices]

- Are you doing that follow-up,

or they're encouraged to do that in their own life

with the various people in their life?

- Both.

So we do that explicitly in the follow-up,

where we have these discussions.

Depending on what the situation is,

you might encourage the person to kind of follow-up.

It's really, the basics of it is, is supportive therapy.

It's non-structured.

It's use all the reflective listening,

and the sort of the humanistic psychology thing,

unconditional positive regard for the person.

But I think, if someone feels inclined

to apologize to their sibling about some things,

like, yeah, go ahead and call 'em up.

With something big, like a relationship change,

I'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- - Do you also tell them

not to start any relationships?

- I don't remember that ever coming up.

- Interesting. - But if it-

- I'm not joking.

I was just wondering, you know?

- Yeah. - But it makes sense

why you would want- - Like if they're dating,

and they're thinking like,

ah, it 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? - Yeah,

don't get a puppy. - And let your sober mind-

- Don't get a puppy.

Certainly, don't get four puppies

until your... [Dr. Matthew laughs]

I have a question about flashbacks.

- Uh-huh.

- You know, one of the kind of things

you hear is flashbacks,

and that people- - Yeah.

- Do people get flashbacks?

And if so, what is the basis of flashbacks?

The on-the-street lore about this,

is that, somehow, some of the compound

gets stored in body fat tissues,

and then released later.

Like, is that complete nonsense?

- No evidence for that,

so probably complete nonsense.

- Flashbacks are nonsense,

or the storage in body fat is complete nonsense?

- 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,

a very small number of people percentage-wise

who have used psychedelics,

will have these persisting perceptual disorders,

like they'll see halos around things.

They'll see some trails,

like the after image is 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,

the people in psychedelic studies with LSD,

psilocybin, mescalin,

and it's never been seen in the Modern Era,

again, now with thousands of participants

at a number of centers like ours throughout the world.

So it seems to be something that is,

for some reason, happening in illicit use.

So now that brings in,

okay, is there polypharmacology?

- Right. - You know,

'cause you're drinking- - Did you take

what you thought you took? - Yeah.

What's the dose?

What's the purity? - Yeah.

- But then also, what I think is actually even more so,

and 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 had hallucinogen history.

And the amazing thing about this,

is that a number of people

seem to have straight up

HPPD diagnosis. - What is HPPD?

- 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 proceeded by any of those substance uses.

So I think it's...

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.

- Yeah. - A psychedelic-

The same way that a life experience

can destabilize this - Sure.

- person more easily.

I think of it like that.

There's probably some

pretty rare neurological susceptibility.

We have tended, 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.

It's always the weird other thing that gets the attribution.

You don't attribute to the thing,

like, oh yeah. did you smoke cigarettes?

Did you drink?

It's like, well, yeah,

but I see lots of people drinking,

and not ending up with this.

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 you remember,

several years back, - Oh, yeah.

What was the deal with that? - 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.

Yeah, it's one of the crazies- - While the person was alive?

- 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 salt stuff

that's been going on".

The only thing- - What was it?

- [Dr. Matthew] The only thing

in his system- - Well, maybe we can

set the record straight for people.

What was this...

Why would he say bath salts,

and was it bath salts? - It wasn't.

And so the only thing in his tox was cannabis,

which we all know,

typically, people don't eat people's faces off

after they get stoned. - It makes you hungrier,

but not that hungry. - [laughs] Yeah.

Right. - Yeah.

- 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 off.

So we're just so ready to latch on.

Just like the people of another culture that we don't know,

it's very easy to assign attribution

to a class that you're very unfamiliar with.

So I think they, 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.

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 experiences 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.

So someone used mushrooms a week ago,

now they do something like they smoked some cannabis,

or they take a warm bath,

or they're simply relaxed,

and 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 of state-dependent learning.

It's not the distressing component that is in,

and it's typically not perceptual.

And then another class are just sort of

perceptual anomalies within a day

or two following the experience, which is not HPPD.

Most people have joked that this is a free trip.

Like you might see a few trails or halos the day afterwards.

It doesn't last longer than that.

And it 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.

- Got it. - So the flashback is...

Yeah- - Interesting.

No, I appreciate you clarifying that.

I mean, one very common misconception about neuroplasticity

is that it's an event.

And it's not an event, it's a process.

And we have no understanding

of the duration of that process.

However, the experience of any drug

or any life experience, right?

Even if it's a trauma, or a wonderful experience,

or a psychedelic experience, it doesn't matter,

sets in motion a series of dominoes that fall,

and it's the falling of those dominoes

that we call neuroplasticity.

I mean, the reshaping of neural circuits could take years.

We don't know.

It's the trigger,

and then there's the actual change.

And so I think that some of what you described

could be, literally, the reordering of circuitry,

that in some individuals, might extend longer than others.

And there is one phenomenon

that I've been told people experience,

and I'm wondering whether or not any of the

patients you've worked with,

or people in your trials have 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. - So it's DMT,

the active- - Right.

- It's orally- - Excuse me, that's right.

- It's NAO inhibitors - Of course.

Of course. - that allow the

- Yeah. - DMT to be orally-

- Right, I should've 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've 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

like a shiver down their spine,

or up their spine, consciously.

You know, 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 like a cooling,

cooled perception. - Yeah.

- 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,

'cause it's actually somewhat pleasurable.

And this is a

well-known phenomenon, ASMR. [Dr. Matthew laughs]

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 in

to a kind of deeper sense of somatic self.

Now, on the internet, ASMR, if you look it up,

it's a little bit like the bath salt thing,

but in the other direction.

Like there were 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...

Like, for instance, there's people that will go listen to,

it seems to be women in particular,

whispering about like car mechanics, or something,

or scratching.

So there are certain sounds that will do this.

Whispering, tapping, finger tapping.

And people experience immense pleasure from it.

It's not really sexual pleasure,

but it's this kind of

deep core of the body. - Yeah.

- It's the autonomic nervous system down in the

curve of the spine. - Probably what a

certain number of people would call Kundalini,

which is another one- - Right.

- Scientifically who'd...

Yeah. - That's right.

- Yeah. - 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.

- Ah!

- That they're literally...

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.

- Have any studies been done? - No.

- I would imagine, that person might actually like...

Would they duck?

- Oh, what- - If they're-

That would be

an interesting experiment- - And that would be

the kind of thing my lab

would want to get into. - Where they could-

- That's right. - Yeah,

their body could clear, - Right.

Right. - but their projection

- Yeah. - wouldn't?

- 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.

- Oh, yeah.

Yep. - This is very sad,

and fortunately, very rare,

but also a very sad condition.

Anyway, I think that 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 kind of,

forgive the term [chuckles],

baked into 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. - Yeah [laughs].

- But if we could,

I'd like to just ask about

some of the more dopaminergic compounds.

In particular, MDMA. - Yeah.

- My understanding, is the MDMA

is a purely synthetic compound,

that you're not going to find MDMA in nature.

- So far.

- So far. - There are certain-

DMT was first synthesized in the lab,

and then we thought it didn't exist in nature,

and then Richard Schultes found it everywhere

[laughs] in South America. - Yeah, actually-

Yeah- - So who knows,

a plant out there - Right.

- might be making MDMA. - Right.

Right. - But as far

as we know now, no. - Right.

And we'll talk about DMT and its sources within the body.

But MDMA could exist in elsewhere, but has been synthesized.

And my understanding, is the MDMA leads to

very robust increases in both dopamine

and serotonin simultaneously,

which, from a neural networks perspective,

is a very unusual situation, right?

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

- Yeah. - kind of

neurochemical states,

but they're always - Yeah.

- at different levels.

So why would it be,

that having this increased dopamine and increased serotonin

would provide an experience that is beneficial?

And how do you, 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?

- Yeah, yeah.

In terms of the effects, generally,

on serotonin and dopamine,

I can only speculate sort of,

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 sort of control from the amygdala,

in terms of one's experience of memory,

so it may be part of this sort of reprocessing,

this reconsolidation of these memories in a different way,

where the amygdala is not like going crazy,

saying, freak out,

like fight or flight.

- What I should have said,

it seems like MDMA is being used clinically, anyway,

mainly for trauma, - Right.

- not just for depression, sorry.

- Although part of that, we really don't know,

and maybe the 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- - What do you mean

by underground?

Oh, because they're doing it- - People doing illegal,

- Yeah. - but more like

a professional therapist would.

It's just illegal.

And this is a kind of 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,

like really freaking out,

is much lower with MDMA.

People can have bad trips,

but they're of a different nature.

It's not- - Well, what is-

- It's not sort of like freaking out,

because all of reality is sort of 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 like this is...

Like get me off this- - You're talking about LSD

or psilocybin? - LSD, psilocybin,

ayahuasca. - Bad trip.

- Yeah, yeah.

And just this sense of like, I'm going insane.

This is so far beyond anything I've ever experienced,

and it's scaring the shit out of me.

- How often does that happen? - I don't have a toehold

on anything, - Yeah.

- even that I exist as an entity,

and that can be really...

I think, frankly, experientially,

that's kind of the gateway to both

the transcendental mystical experiences,

the sense of unity with all things,

which we know our data suggests

is related to long-term positive outcomes.

- Wait, I want to make sure I understand.

So you're saying, the bad trip can be related

to the transcendental experience?

- Right, I think those are both,

speculating, but you have to pass through

this sort of like reality shattering,

including your sense of self,

and one can handle that in one of two ways.

You can either completely surrender to it,

or you can try to hang on,

and if you try to hang on,

it's going to be more like a bad trip.

So again, I wish there was more,

and hopefully, there will be more, experimentation.

There's a lot going on here in the black box,

in terms of the operant behavior of how you are

within yourself choosing to handle letting go, you know?

And eventually, we'll be able to see this in real time

with brain imaging.

Ah, there, they are surrendering

to the psychedelic experience.

Here, they are trying to hold on.

But we 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,

even compared to the others, 'cause it forces people.

There is no choice

to hang out. - I've never done it.

- Yeah. - I was told

that DMT is like a high-speed locomotive

into the psychedelic experience,

and out of the psychedelic experience,

- [Dr. Matthew] Yeah.

- and there's no ability to hold onto the self

while you're in the kind of peak phase.

Is that correct?

- A lot of people say that.

Terence McKenna, who's kind of 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 like,

what is the self that's changing?

What is the rest of the world?

- Well, and Languages is totally deficient

to describe experience anyway,

much less on a psychedelic.

What is McKenna's background?

What is his qualification for being this,

as you referred, this bard of DMT

and psychedelics? - And we're talking

about Terrence, and there's also the brother, Dennis,

whom I know, whose- - Can only imagine

what Thanksgiving dinner - Yeah, they're brothers.

- is like at their house. - Terence passed away years,

a couple decades ago now.

But he's sort of the one who's known as being a bard,

and you can find hundreds, if not thousands,

of hours of him on the lecture circuit

in the '80s and '90s on YouTube.

But his background was really...

Oh gosh, I don't recall what his college degree was in.

But he basically, when he was 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, what they recognized,

and just took a lot of mushrooms,

and- - And talked about it?

- Talked about it.

And Terence was basically very intelligent,

very well-read in literature

and culture person that could...

He was sort of 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 serves, like 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.

Like, it's right there.

It'll take five minutes.

It'll shake everything in your reality.

You know, he would sort of goad people into doing it.

- Well, certainly, science and clinical medicine is,

are just but two lenses with which to explore

these things in life.

Well, part of the reason I ask is,

I feel like,

in the world of health and fitness,

you have this very extreme condition

of like Arnold Schwarzenegger's and bodybuilders

who have 2% body fat,

and they look like, to most people,

they look kind of freakish, - Yeah

especially now, right?

- Oh, especially now.

- Especially now. - Yeah, yeah.

- And yeah- - Made Arnold look

- Yeah, yeah. - like regular-

- Exactly.

- Back in his day, yeah. - Yeah.

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,

but except that they get really bendy,

but it's a community that included lifestyle practices,

and nutritional practices, and then drug practices.

From those very extreme subcultures,

there's been an export,

which is that weight training is healthy, right?

The general public has done that.

Or that yoga is healthy.

- Yeah. - 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.

Look, I'm from the Bay Area.

I'm not far from the Midland Park VA,

where "One Flew Over the Cuckoo's" is

basically, based on, right? - Oh, yeah.

- Ken Kesey and those guys.

There has been an attempt at creating this movement toward

openness about psychedelics

and their positive effects.

This has happened before.

- Yeah. - 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.

The other guys who were at universities lost their jobs.

They were actually removed from places

like Harvard and other universities

for their kind of cavalier explorations.

Right? - Oh, yeah, mm-hmm.

- And now, things are kind of returning.

So in the same way that bodybuilding led to

weight training in every corner gym,

- Yeah. - men, women, and children,

and contortionism is one extreme,

but people generally think that yoga

is a pretty healthy practice, right?

These are matter of degrees, right?

And now, here you are - Yeah.

- inside the walls of a

very highly respected university, Johns Hopkins.

You're on the medical school side,

- Mm-hmm. - or the undergrad?

- So in the med school, - Medical.

- which is a serious health institution.

The question is to me,

what are the valuable exports, right?

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. - Yeah.

- And what's so striking to me,

is the elements of atypical experience,

atypical representation of the self.

So for the average person, right?

Or for kids that are hearing this.

Kids that are in their teens, right?

- [Dr. Matthew] Yeah.

- I want to talk about, what are the dangers of psychedelics?

It's something you don't hear a lot about these days,

and it's not because I'm anti-psychedelic at all,

but what are the dangers, right?

If a kid or adult has a predisposition toward, let's say,

psychotic thinking, right?

Or auditory hallucinations? - Yeah.

- Whereas on the Asperger's side of the autism spectrum,

is there an increased risk

of bringing the mind into these states?

'Cause 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?

- Yeah.

So these can be profoundly de-stabilizing experiences,

and ones that, ideally, are had in a safe container,

sort of where someone...

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 have been labeled as 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 of,

I always think of Syd Barrett,

the first singer of Pink Floyd,

seems pretty clear.

Although, I think the family- - I don't know

what happened there.

- So he- - I should be...

Sorry, Pink Floyd fans.

I've never...

The songs are just really long.

- Yeah, you're more of a punk guy, right?

- Yeah. - Yeah.

[both laughing]

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 of

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.

Yeah.

And when do people start playing with drugs?

[laughs] 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. - Do the people around

those schizophrenics say it's helped them,

or just- - I don't know.

- 'Cause when schizophrenics say things,

you have to- - You have to weight it.

- I mean, with all due compassion

and respect for schizophrenia,

it's a disorder of thinking.

So if they're saying, it helped them?

- 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,

and 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... [Dr. Huberman mumbles]

That may never be the case,

but even if it is,

you'd have to be even more cautious

and figure some more things out first

with some of these other disorders.

- What about bipolar? - 'Cause it seems-

- Bipolar disorder, can it be exacerbated

by these compounds? - Yeah, and it's-

It may be that, sort of 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.

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- - But it reshapes circuitry.

I mean- - 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...

You know, some people with that psychotic predisposition,

they lucky to be born to a great family,

a stable environment.

They maybe never have a full break,

or the one that they have is not nearly as bad

as what someone who's homeless,

and is coming from all kinds of early childhood trauma.

The disease is probably going to be far worse.

Having a psychedelic experience

is like one of those de-stabilizing 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 like, say,

a first degree relative.

In some studies, even a second degree relative.

Given the heritability,

there's some increased chance

- Sure. - if your brother or your...

Yeah.

So in an abundance of caution,

even eliminating that...

I think, eventually, if it's approved for use, FDA use,

we could dial back on that as we learn more.

I think, it's, again, overly cautious,

which is- - But you're doing

an early stage

clinical trial, so. - 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,

like you could very reliably determine

that this person has either a psychotic disorder,

or bipolar disorder, or a strong predisposition.

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 of 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'd- - At some point

within the entire journey.

- Right. - Yeah.

- Now, they could have

one of the most beautiful

experiences of their life, sometimes,

like a couple of minutes later.

- Right. - 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 taken 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,

[mumbles] is better than having nothing.

So very dependent on context.

And so the tough thing here

that in conveying to the public is that,

a lot of folks will say,

man, I've taken psychedelics hundreds of times,

and this is like you're fear-mongering,

and there's no,

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.

Or gosh, one of the craziest cases was a kid,

like an 18-year-old or so, in Oregon,

several years back, that just...

He even wrote about, I want to take the biggest...

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 and ended up killing him,

and it was just tragic.

Obviously, an overuse of force in that case,

'cause he was actually naked at the time.

This naked like 120 pounds, I think, as I recall, kid

that ended up dying.

But- - Well, it's analogous

to the reason I used the examples of bodybuilding culture.

I mean, people there have taken

excessive amounts of anabolic and diuretics, and died.

Then the contortionist culture,

people would put themselves

in the little plexiglass boxes to do...

At the extremes,

you're going to get deaths,

and at the extremes - Right.

- 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'd create extremes through dosage, right?

It seems. - Right.

- 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? - Right.

What model.

Yeah. - Right, I mean,

again, we'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 there's contortionism in a plexiglass box,

and thinking of Houdini, - Right.

- or something.

These are a matter of degrees.

Speaking of dosage, I definitely want to ask you

about microdose versus standard or macrodose.

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 work

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.

- Yeah. - It's a mini dose, right?

And yet, some of these compounds

are tremendously powerful at microgram concentrations.

So what constitutes a microdose,

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 macrodosing?

- Yeah.

And so LSD would be the prototypical example

of that super potent compound. - Yeah, how much am I-

What size dosage of LSD will lead to hallucinations,

and kind of standard- - So sort of 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.

Again, thinking you're talking to

the person that's not there,

seeing the pink elephant.

But pseudo hallucinations- - It's more like tracers

and things like that. - Right.

- Perceptual blending. - Yet, 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,