April 18, 2024 • 32 mins
Psychedelics are going mainstream. The FDA has approved ketamine for certain patients with depression, and may soon approve MDMA for post-traumatic stress disorder (PTSD). But a fundamental question remains unclear: How do psychedelics work?
Gul Dolen is a professor of psychology and neuroscience at UC Berkeley. In a series of experiments, Gul has found evidence of a common mechanism that a wide range of psychedelics use to affect the brain. If Gul is correct, these drugs may be useful not only for people suffering from mental illness, but also for people dealing with neurological problems like strokes.
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Episode Transcript
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Speaker 1 (00:15):
Pushkin. Let's talk about psychedelics. It's been a few years
since the FDA approved the use of ketamine to treat
depression in certain patients. Later this year, the FDA may
also approve the use of MDMA in combination with therapy
(00:35):
to treat PTSD post traumatic stress disorder, and researchers around
the world are studying other powerful psychedelics like psilocybin, ibogaine,
and LSD. It's been clear for a long time that
these are very powerful drugs, and it's becoming clear that
these drugs may be particularly helpful in certain contexts. But
(00:58):
still less clear is a very big, very important question,
how exactly do psychedelics work. I'm Jacob Goldstein and this
is What's Your Problem, the show where I talk to
people who are trying to make technological progress. My guest
(01:19):
today is goul Dolan. She's a professor of psychology and
neuroscience at the University of California at Berkeley. Goule's problem
is summed up in a phrase from a paper that
she co authored last year in the journal Nature. She's
trying to identify quote, a common neurobiological mechanism that can
(01:39):
account for the shared therapeutic effects of psychedelics. In other words,
why do all these very different drugs seem to have
similar powerful effects on the brain. Goole has a theory
about this, about why all these different drugs seem to
have similar effects, and if she's right, it could mean
that psychedelics used in the right context, may be useful
(02:02):
beyond mental illness. Goul thinks, among other things, psychedelics may
be able to help patients recod from strokes. We started
the conversation talking about the origin of Ghul's quest to
understand how psychedelics work.
Speaker 2 (02:19):
About ten years ago when I started my lab, you know,
there were starting to be some hints that psychedelics were
having these remarkable effects in you know, all kinds of
diseases that didn't seem terribly connected to each other, right,
so addiction and depression and PTSD, and you know, the
people who study those diseases each have their way of
(02:39):
studying them and modeling them in animals, and they're they're
siloed into different spaces. And yet we were starting to
hear hints that, you know, it didn't matter which psychedelic
they were kind of interchangeably showing some promise in all
of these different areas that seem unconnected to each other.
I mean not just in terms of what behavioral essays
(03:01):
we use, but even sort of what brain regions might
be important. Right, Like, the depression people were focused on
the hippi campus and the frontal cortex.
Speaker 3 (03:10):
The PTSD people.
Speaker 2 (03:11):
Were focused on the amygdala, the you know, the addiction
people were focused on the nucleus, thecumbents, and they were
just sort of all over the place, and yet there
seemed to be this overlap. But when we then discovered
that all of the psychedelics seemed to be doing the
same thing, it sort of began to settle in that
this explanation that we came up with could account for
(03:35):
why all of these diseases that look so different from
each other could be responding to psychedelics in a therapeutic way.
Speaker 1 (03:43):
So should we start the explanation with talking about critical periods?
Is that a reasonable place to start. Let's start with
critical periods. What's the critical period?
Speaker 3 (03:52):
Right?
Speaker 2 (03:53):
So, critical periods are something that you know, neuroscientists have
known about for almost one hundred years. They were first
described in nineteen thirty five by Conrad Lorenz, who was
describing and imprinting behavior in baby geese, So basically, forty
eight hours after they hatch from their eggs, they will
imprint onto anything that is moving around in their immediate environment.
(04:17):
So typically this would be their mother, but you know,
if there's a crazy scientist around, it might be to
the crazy scientist.
Speaker 1 (04:23):
And there are photos of the baby geese following him
around right in fact, as if he were a mamma goose.
Speaker 4 (04:29):
Yeah, exactly.
Speaker 2 (04:31):
And so but that window of time where they're so
sensitive to their environment and they form these lasting attachments
only lasts about forty eight hours, and then afterwards they don't.
They're not sensitive to their environment in the same way.
They're not learning from their environment in the same way.
And that window of time Conrad Lorenz called it the
critical period. And since that time we've discovered literally dozens
(04:53):
of other critical periods. So there are critical periods for
rewiring the visual system, critical periods for touch, critical periods
for movement, critical periods for language. Language is probably the
one that most people are familiar with. If they try
to learn enough their language when they were older, it's
much harder and you always have an accent compared to
(05:13):
the language you learn as a child, and so neuroscientists
have known about these critical periods for a long time,
and we've had this idea that maybe the reason that
we're so bad at curing diseases of the brain, neuropsychiatric
illnesses and neurological diseases, is because by the time we
get around to correcting whatever is the underlying problem, the
(05:38):
relevant critical period.
Speaker 3 (05:39):
Has already closed.
Speaker 2 (05:41):
And so the classic example of this is if you
are born with bilateral cataracts in your eyes and you
don't have them removed by the time you're aged five
or so, then you will be blind forever because even
if you remove the cataracts, wants the ability of the
visual part of the brain to adapt to the corrected
visual environment. Once the critical period has closed, it can't
(06:04):
adapt again, and so even though the impediment is removed,
the brain can respond to it, and so you're blind forever.
And so we have been looking, probably for the last
one hundred years or so for ways to reopen critical periods,
with the idea that if we could reopen them, we
could potentially cure or do a better job of correcting
(06:27):
some of these impairments later in life.
Speaker 1 (06:29):
So in this Nature paper, that you published last year.
You write, it's tempting to speculate that the altered state
of consciousness shared by all psychedelics reflects the subjective experience
of reopening critical periods. Let me say, first of all,
I like, it's tempting to speculate. It's like, you're not
(06:50):
even speculating.
Speaker 5 (06:51):
It's more speculative than speculating, right, Like, we're not going
to speculate, but we're tempted to speculate. So and I
appreciate that, right, Like, this is clearly speculative, it's based
on research and mice. But why are you tempted to
speculate that psychedelics may reopen critical periods in the brain?
Speaker 3 (07:09):
Right?
Speaker 2 (07:10):
So, the reason that we're tempted to speculate this is because,
you know, one of the other things that brings together
psychedelics as a group of drugs is that they all
induced this altered state of consciousness. So we discovered a
critical period in twenty nineteen for Social rewards learning. It
(07:30):
was a brand new critical period. Although you know, there
was a lot of literature from human studies suggesting that
such a critical period should exist, but it just took
doing it. In nine hundred mice to be able to
formally demonstrate it. So we did that. We showed that
there's this social critical period, and originally we showed that
MDMA was able to reopen this critical period. And we
(07:53):
thought because MDMA is characterized by having this pro social
property that makes it different from the other psychedelics in that,
you know, it's altered state of consciousness, plus you know,
cuddle puddles and empathy, right, and so we thought it's
because of that pro social property of MDMA that it's
(08:13):
able to open this social critical period. But then when
we figured out that well LSD and I began and KETYMI,
none of which are like particularly pro social, nobody's you know,
doing a thirty person cuddle puddle on I begin right,
even though they don't have this pro social property, they
are all also able.
Speaker 3 (08:32):
To open this critical period.
Speaker 2 (08:34):
And so that was our first hint that maybe the
common property is between psychedelics that accounts for this altered
state of consciousness that they all induce is the common
property of inducing critical period reopening.
Speaker 1 (08:52):
And so specifically, can you just talk a little bit
more about the specific critical period in mice that you're
looking at here, right?
Speaker 2 (09:01):
So, we're measuring something called social condition place preference, which
is just an assay to measure the ability of the
mice to learn from their social environments. And so that
ability changes over time, and as they get older, they
stop learning from their social environment. And so this developmental
(09:22):
change relates to why we think teenagers are so much
more susceptible to peer pressure than adults. We think it
relates to why you're so much more sensitive to learning
the rules of your culture when you're young, so you know,
you learn what's polite.
Speaker 1 (09:37):
So it's basically the idea is that there's a critical
there is some set of critical periods for learning social
behavior from language to norms, and that that those clothes
over the course of childhood and adolescents.
Speaker 3 (09:53):
That's right, that's right.
Speaker 2 (09:55):
And we think that that critical period, like other critical
periods like language, you know, is curtailed as you get
older because basically it's sort of expensive energe to always
be having to learn from your social environment.
Speaker 3 (10:13):
You know, I like to.
Speaker 2 (10:15):
Think back on my teenage years and you know, mostly
I'm relieved that they're over, because you know, it was
time consuming and energetically exhausting to you know, have to
care about the exact right shade of acid washed genes
that the cool kids are wearing.
Speaker 1 (10:30):
Right, and now you wear whatever acid wash genes you want, right,
that's right.
Speaker 4 (10:34):
I wear mom jeans that are acid washed.
Speaker 1 (10:39):
And so then you find that when you give psychedelics
to an old mouse, they're able to the.
Speaker 2 (10:47):
Learning that they were doing in juvenile in their juvenile
period return, so they're able to learn again like a juvenile.
Speaker 1 (10:55):
Have you tested this theory on other critical periods in
mice or on other animals?
Speaker 2 (11:01):
Yeah, So basically, as soon as we got this this result,
I reached out to every single person that I know
who works on critics periods, and I was like, do
you have a critical period that you want to try
and reopen? Because I think we might have accidentally stumbled
on the master key for unlocking critical periods, and so
we're working on it. We definitely have some collaborations going.
(11:24):
But in the meantime between sort of when we first
have this twenty nineteen paper and then this summer, there
have been some hints that other critical periods are being
reopened by say ketamine. There are two papers showing that ketamine,
if given back to back to back to back can
reopen the critical period for ocular dominance plasticity, which is
(11:47):
this visual critical period that we've learned so much about
the mechanisms about. So that's a first hint, and we
are working feverishly to see if we can reopen other
critical periods like motor learning for stroke. We're doing that
in both mice and in humans. We're working on some
language critical periods in collaboration with some of the labs.
(12:09):
So you know, the jury is still out, but there's
some other reasons to make us think that we're on
the right track with this idea about the master key.
Speaker 1 (12:20):
When you say master key in this context, in this context,
exactly what do you mean?
Speaker 2 (12:25):
So I guess what I mean is is that when
I was a graduate student, we were a little bit
in a debate with another lab that was proposing that
there would be some drug or manipulation that you could
do that could reopen all critical periods, and that you
could just give that drug and it would it would
(12:48):
it would be the master key, right and for unlocking
all of these critical periods. And at the time, I
remember being really skeptical of that idea, and I thought, well,
anything that can do that to the brain is either
going to induce amnesia, cause seizure, or disrupt the structural
integrity of the brain. And I thought that because of
(13:11):
what we knew about, you know, basically the mechanisms that
constrain critical periods to these windows of time, like like.
Speaker 1 (13:19):
You couldn't work without breaking the brain. The only way
to reopen the critical period is the master key is
like a sledgehammer that's just gonna totally break everything. So
why even bother.
Speaker 2 (13:29):
Right, And I you know, I called it the Melti
brain problem, right, And so then when we when we
started getting these results for the psychedelics, I was, I
started thinking, well, how come we're not running into the
Melty brain problem? And I think, and this is at
this point still speculative, and we're we're actively pursuing this
(13:50):
line of research. So I don't want to overstate the case.
But my hunch is that the way that we are
able to circumvent, or the way that psychedelics specifically are circumventing,
the Melty brain problem is that they are context specific.
So it's not that psychdelics are causing reopening of all
(14:12):
critical periods everywhere in the brain all at the same time.
It seems to be that they are not you know,
destroying or melting the brain, because they're only making available
for modification the subset of synapses, circuits, memories, and grams
(14:34):
that are have been recently activated, and that is why
they have this constraint of being context dependent.
Speaker 1 (14:42):
So this is this is why your thesis is they
will psychedels will be helpful when paired with interventions like therapy,
but not by themselves.
Speaker 4 (14:53):
Well, this is.
Speaker 2 (14:56):
This is the explanation we have for why the psychedelics
aren't breaking the the brain rather than I mean, basically,
the clinical data is driving this idea that in fact
the context matters, right.
Speaker 1 (15:12):
But it's a potential mechanistic explanation for that.
Speaker 2 (15:15):
Clinical well that feature, that's right, it's a mechanistic explanation
for a clinical description, which you know, I don't think
is going to be the case for every single application
that psychedelics might be used for. So, for example, I
think the critical period idea nicely explains why MDMA assisted
psychotherapy works. If we're able to demonstrate that we can
(15:37):
correct motor impairments following stroke with psychedelics paired with physical therapy,
then that'll be a nice other explanation.
Speaker 1 (15:47):
That's a huge idea. You've just dropped in the middle
of a list, by the.
Speaker 2 (15:52):
Way, right, So, by the way, that's also quite quite speculative.
Speaker 1 (16:00):
After the break, how gool plans to test this hypothesis
that psychedelics may help patients recovering from strokes. Let's just
talk about how we get from this sort of you know,
(16:23):
seems like psychedelics reopen one critical period in mice to like,
can this idea be helpful in humans?
Speaker 4 (16:31):
Right?
Speaker 1 (16:33):
You must know the aphorism mice lie and primates exaggerate.
I was thinking of that one.
Speaker 2 (16:39):
I mean, I think that a little bit of why
it's so hard to translate this stuff from mouse studies
to human studies so far is that mostly what they've
been used for is non psychiatric disease, and so it's
really sort of impossible to measure or to recapitulate all
(17:00):
of the features of a psychiatric disease.
Speaker 3 (17:03):
In a mouse. Right, Like if.
Speaker 2 (17:04):
PTSD is mostly in humans and females is caused by
you can't really model rape in a mouse, right, And
so there are all these other features of the illness
that you know, you can try and approximate by fear learning,
but you're not really going to capture the salient elements.
And so this is kind of why I think an
(17:26):
important test case of this idea of the master key
is to switch away from neuropsychiatric disease and move into
neurological disease, because then you know, we can explicitly test
this learning model. Right if we switch to a neurological
disease like stroke, and we're able to show that if
(17:47):
we give psychedelics and pair it with physical therapy, we
are able to restore motor learning. But if we give
psychedelics and then just send them on home without any
additional physical therapy, then nothing really is going to happen.
That I think would be an explicit test of this
idea that what the mechanism at work here is about
(18:09):
learning and memory rather than a magic bill that corrects
an underlying biochemical imbalance.
Speaker 1 (18:15):
Well, yes, I mean that's the side of it, addressing
this debate that you're involved in, but also going on
there presumably if you're able to do this test in
stroke patients, is if psychedelics plus physical therapy after a
stroke leads to better recovery than physical therapy alone. That's great.
I mean, I don't even care about the mechanism at
(18:35):
that point, right, Like, is somebody going to do a
phase one safety trial soon? Like is somebody going to
give stroke patients psychedelics?
Speaker 4 (18:44):
We are, we are working on it.
Speaker 2 (18:46):
Right after this call, I have a meeting to try
and secure funding to make that happen. So we are
on it, and we are actually doing it in parallel
with mouth studies for mechanism. And you know, I understand
why people are so much more jazzed about you know
the clinical outcomes and you know the real world impacts
of these things. But I have to say, I think
(19:08):
mechanism should not be underestimated as an important way of
understanding this, because we never would have even come up
with this idea of thinking about stroke if we hadn't
thought of the mechanism. Right, So, if we the mechanism
is what is leading us to speculate, if this mechanism
is true, then these other diseases should respond in this
(19:30):
predictable way.
Speaker 1 (19:31):
There was a better way I could have framed that,
And I apologize. I mean, what I really mean is, yes,
it's it's useful and big to learn the mechanism. But
like helping stroke patients get better is also a huge deal.
Would perhaps be diplomatic way to say that.
Speaker 2 (19:48):
I mean, I don't mind the undiplomatic way, because that's
I've been dealing with this right from the beginning.
Speaker 4 (19:53):
Right.
Speaker 2 (19:53):
So, the first time I presented this critical period idea
at a meeting, it was in Portugal, and you know,
the room was full of people who were already doing
clinical trials for psilocybin for depression and MDMA for PTSD,
and they were already very much invested in the idea
that it was going to work based on some underground
(20:14):
therapists results and anecdotal reports, some of their you know,
pilot studies, and they were like, why do we need mechanism?
Speaker 4 (20:22):
Who cares?
Speaker 2 (20:23):
We know it's going to work, and going backwards to
look in mice seems silly.
Speaker 4 (20:27):
We know it's going to work. It's just the way
to die.
Speaker 2 (20:30):
And I said at that time it was like, mechanism matters,
and there are going to be a million different ways
that we might fail if we don't understand exactly how
these drugs are working. And basically that prediction ended up
being true because the two people who were represented in
that room were on the one side, the people arguing for,
you know, let's just use psilocybin like a next generation SSRI,
(20:53):
and their trial failed. And then the other half of
the room where people who were saying, no, we need
to pair it with psychotherapy, and their trial was successful.
And our mechanism, we think explains the difference between them.
Speaker 1 (21:06):
Is there an animal model you can use is to
test your hypothesis that in stroke patients psychedelics plus physical
therapy would work better than physical therapy alone.
Speaker 2 (21:20):
Yes, So basically, one of the people I reached out
to when you know, we first got this critical period
result for all of the psychedelics. We're two neurologists at
John Hopkins, so Steve Zeiler and John Krackauer, and Steve
Zyler especially had been working on developing a mouse model
of stroke. And what he has shown is that just
(21:43):
like in human patients with stroke, right after the stroke,
there is a critical period that gets reopened and some
amount of physical therapy is able to restore function, but
that that is time limited. So in my you know,
within seven days after the stroke, they're no longer able
to learn. In humans that's a little bit longer. So
(22:04):
you know, in humans. After your stroke, you're able to
benefit from therap physical therapy for about two months. At
about three months it goes away, and that window of time,
you know, it's closure. And people have thought about, well,
you know, nobody has dreamed big that we might be
able to reopen it. But people have tried to do
other manipulations that might keep it open longer, you know,
(22:26):
by enriching the environment, by you know, giving them SSRIs,
and none of those things have worked.
Speaker 1 (22:32):
It's the injury of the stroke itself is inducing the
brain to reopen the critical period that has been closed
since childhood, and that allows people to whatever, try and
relearn language, try and relearn motor skills whatever they have
lost in the stroke. Obviously not always successfully.
Speaker 3 (22:50):
That's right.
Speaker 2 (22:50):
And basically until this this psychedelic idea came around, the
most effective way to reopen the critical period for motor
learning after stroke was to give another stroke, which is
not you know, very therapeutically viable, right Like, nobody wants
to hear their stroke with another stroke. So this idea
is testable and we are in parallel testing it in
(23:14):
collaboration with the Xylor lab. This is not a social
critical period this is a motor critical period. So let's
test the idea that in this context what matters is
the motor learning or the practicing a motor task, not
the social And so we're testing that and combining with
different psychedelics, but we're comparing all of those different conditions
(23:34):
to test this idea in mice, and then in parallel,
we will do the study to look at you know,
trying to reopen in humans.
Speaker 1 (23:43):
And so the mouse study is underway now, and you're
trying to get funding for the human study, that's right.
And then once you have the money, then you go
to the institutional review board and say can we do this?
Speaker 2 (23:55):
Yeah, you know, everything's queued up and wow, you know,
everything is basically ready to go.
Speaker 4 (24:01):
We just need the money.
Speaker 1 (24:03):
So non trivial, but it's a lot probably surmountable.
Speaker 4 (24:08):
Yeah, yeah, I mean it's a lot of money.
Speaker 2 (24:10):
We're asking for a million dollars to run, you know,
a safety trial and about twenty people. And then if
that phase one trial goes well. The way the trial
is designed is that it will allow us to collect
just a little bit of in addition to how well
this patient population, right, because these are older people who
have other medical issues, so we just want to be
(24:32):
double sure that you know, these drugs are safe in
this population. But the way we've designed the trial is
it'll give us some hints about efficacy, so we'll test,
you know, a little bit of you know, their ability
to recover motor function. And the most important thing about
the human trial and the way that I the reason
that I paired up with Steve and John is because
they have actually developed a sort of gamified virtual reality
(24:56):
context for delivering this physical therapy. It's a virtual reality
kind of room, and the cameras track the person's body
position in space, and as they move their arm around,
a dolphin on a screen moves around, and it's sort
of a fun way to get people to practice moving.
But it's also a little bit more play like, which
(25:19):
is more the way that we learn during our childhood.
So there's this shift in the way we learn between
childhood and adulthood from exploratory learning to sort of goal
directed exploitatory learning, and so we want to kind of
mimic that as much as possible, to make it fun
(25:39):
and to make it not be goal directed.
Speaker 1 (25:42):
They're already doing that sort of psychedelic adjacent sounding thing
where your arm is a dolphin and you're playing. They're
doing that without psychedelics, and you're like, let's definitely add
some psychedelics to that. I mean, is that not to
be glib about it, but they're already doing that without psychedelics.
Speaker 4 (25:58):
That's right.
Speaker 2 (25:59):
So they have developed that whole paradigm to test the
efficacy of that sort of gamified environment compare to standard
of care, because standard of care is really mostly just
teaching patients how to say the other hand, to zip
their zipper and brush their hand. It's really compensatory, not
(26:22):
trying to bring back the lost motor function. And so
they've done head to head studies of the virtual reality
game version versus standard of care during that open state,
of the normal open state of the critical beers, so
right after the stroke. They've shown that there's better outcomes
(26:43):
if they use this gamified version. And so now we're saying, okay,
let's take all those people who didn't get the optimal
therapy right after their stroke, people who had a stroke
a year ago, and go back and see if we
can reopen this critical period and then give them what
we think is the better therapy in terms of this
virtual reality.
Speaker 1 (27:08):
We'll be back in a minute with the lightning round. Okay,
let's finish with the lightning round.
Speaker 4 (27:24):
Okay.
Speaker 1 (27:25):
What's your biggest professional disagreement with your mother.
Speaker 4 (27:30):
Whether psychedelics can cure allergies?
Speaker 1 (27:34):
Go on.
Speaker 2 (27:35):
Okay, Well, so my mother is an allergy and immunologist clinician.
She's retired now, but you know, I've told her this
crazy idea that we had about psychedelics and she was like, no,
that's not how it works. And the idea is based
on the fact that, you know, there's some evidence to
support the notion that allergy happens because you know, the
(27:58):
immune system, the part of the immune system that's normally
supposed to fight off parasitic infections, is being underutilized by
our modern diets, which are put more parasite free than
our evolutionary history, and so it's sort of left jobless
and it's looking for a job. And my idea is that, well,
(28:19):
maybe the brain is assigning the job and saying that
dog barked at you, that's scary, that's the threat to
go after that immune system, and that if that's a
learned association that the brain decided that it could unlearn
it too.
Speaker 3 (28:34):
By reopening this critical period.
Speaker 4 (28:35):
It's totally speculative.
Speaker 2 (28:36):
I have to say, like, I don't believe it enough
where I'm like out, you know, doing psychedelics and snuggling
up to a horse.
Speaker 4 (28:43):
I would love to cure my horse allergies. But I don't.
I don't believe it enough to go for it.
Speaker 3 (28:48):
I think it's a testable hypothesis that we should study.
Speaker 1 (28:51):
And your and your mom believes it even less than
you do.
Speaker 4 (28:54):
That's right.
Speaker 1 (28:55):
Yes, what's your favorite portrayal of a psychedelics of a
psychedelic experience in you know, in whatever, in a book,
in a movie, in music.
Speaker 2 (29:07):
I really still have a soft spot in my heart
for the Huxley description of him staring at a chair,
because you know, as a scientist, I have to say
that one really resonates. Like I'm not a religious person,
mystical experiences, that stuff doesn't really resonate with me. But
he's staring at a chair and sort of being mesmerized
(29:31):
by the you know, asymptotic distribution of chair molecules the
further away you get from the chair, and then the
Huxley molecules the further and then you know, the two
of them sitting on each other and suddenly they're inert
they're intermixed, and Huxley is the chair.
Speaker 4 (29:47):
I mean that that resonates.
Speaker 1 (29:48):
But have you ever taken psychedelics for work?
Speaker 4 (29:54):
I don't know.
Speaker 2 (29:55):
Yeah, I don't really want to talk about that or
answer that question.
Speaker 1 (30:00):
Mine totally reasonable. Do you have any advice for people
who are considering taking psychedelics recreationally.
Speaker 2 (30:08):
Yeah, it would say that, you know, these are powerful
medicines and that we should honor and respect their power,
and that they're doing something. If we're right, they're doing
something very big to the brain, and that this transformation
should not be taken lightly. And you know, I would
also emphasize that our studies suggest that once you reopen
(30:31):
these critical periods, especially with psilocybin, MDMA and LSD, they
stay open for several weeks after the acute effects of
the drug wear off, and so you're gonna be in
a in a sort of vulnerable state that's reminiscent of childhood.
And I would say be very very cautious about who
(30:51):
you expose yourself to during that period. You know, if
you're in a traumatic relationship, it's probably a good idea
to stay away from your traumatizer for a couple of
weeks after you've taken the drug, you know. I think
that we can learn a lot from the history of
these drugs.
Speaker 3 (31:10):
You know.
Speaker 2 (31:10):
Charles Manson is a good example of somebody who gave
psychedelics to people and then used it to, you know,
when they were in this vulnerable state, which presumably lasted
for a long time, to indoctrinate them into his way
of thinking, and turned a bunch of hippies into killers
who were going to, you know, induce helter skelter to
(31:31):
save the world. This is the sort of awesome power
of these drugs that we need to be very mindful
of and not treat them like little toys.
Speaker 1 (31:43):
Anything else, anything else we should talk about. I know
you've got to go. I don't want to keep you,
but if there's anything else you want to say.
Speaker 2 (31:49):
Please, I think we covered a lot, super fun. Thank
you so much, any.
Speaker 4 (31:56):
Thanks one million dollars.
Speaker 1 (32:06):
Gool Dolan is a professor of psychology and science at
UC Berkeley. Today's show was produced by Gabriel Hunter Cheng.
It was edited by Lyddy Jean Kott and engineered by
Sarah Bruguier. You can email us at problem at Pushkin
dot Fm. I'm Jacob Goldstein and we'll be back next
week with another episode of What's Your Problem.
Pushkin. Let's talk about psychedelics. It's been a few years
since the FDA approved the use of ketamine to treat
depression in certain patients. Later this year, the FDA may
also approve the use of MDMA in combination with therapy
(00:35):
to treat PTSD post traumatic stress disorder, and researchers around
the world are studying other powerful psychedelics like psilocybin, ibogaine,
and LSD. It's been clear for a long time that
these are very powerful drugs, and it's becoming clear that
these drugs may be particularly helpful in certain contexts. But
(00:58):
still less clear is a very big, very important question,
how exactly do psychedelics work. I'm Jacob Goldstein and this
is What's Your Problem, the show where I talk to
people who are trying to make technological progress. My guest
(01:19):
today is goul Dolan. She's a professor of psychology and
neuroscience at the University of California at Berkeley. Goule's problem
is summed up in a phrase from a paper that
she co authored last year in the journal Nature. She's
trying to identify quote, a common neurobiological mechanism that can
(01:39):
account for the shared therapeutic effects of psychedelics. In other words,
why do all these very different drugs seem to have
similar powerful effects on the brain. Goole has a theory
about this, about why all these different drugs seem to
have similar effects, and if she's right, it could mean
that psychedelics used in the right context, may be useful
(02:02):
beyond mental illness. Goul thinks, among other things, psychedelics may
be able to help patients recod from strokes. We started
the conversation talking about the origin of Ghul's quest to
understand how psychedelics work.
Speaker 2 (02:19):
About ten years ago when I started my lab, you know,
there were starting to be some hints that psychedelics were
having these remarkable effects in you know, all kinds of
diseases that didn't seem terribly connected to each other, right,
so addiction and depression and PTSD, and you know, the
people who study those diseases each have their way of
(02:39):
studying them and modeling them in animals, and they're they're
siloed into different spaces. And yet we were starting to
hear hints that, you know, it didn't matter which psychedelic
they were kind of interchangeably showing some promise in all
of these different areas that seem unconnected to each other.
I mean not just in terms of what behavioral essays
(03:01):
we use, but even sort of what brain regions might
be important. Right, Like, the depression people were focused on
the hippi campus and the frontal cortex.
Speaker 3 (03:10):
The PTSD people.
Speaker 2 (03:11):
Were focused on the amygdala, the you know, the addiction
people were focused on the nucleus, thecumbents, and they were
just sort of all over the place, and yet there
seemed to be this overlap. But when we then discovered
that all of the psychedelics seemed to be doing the
same thing, it sort of began to settle in that
this explanation that we came up with could account for
(03:35):
why all of these diseases that look so different from
each other could be responding to psychedelics in a therapeutic way.
Speaker 1 (03:43):
So should we start the explanation with talking about critical periods?
Is that a reasonable place to start. Let's start with
critical periods. What's the critical period?
Speaker 3 (03:52):
Right?
Speaker 2 (03:53):
So, critical periods are something that you know, neuroscientists have
known about for almost one hundred years. They were first
described in nineteen thirty five by Conrad Lorenz, who was
describing and imprinting behavior in baby geese, So basically, forty
eight hours after they hatch from their eggs, they will
imprint onto anything that is moving around in their immediate environment.
(04:17):
So typically this would be their mother, but you know,
if there's a crazy scientist around, it might be to
the crazy scientist.
Speaker 1 (04:23):
And there are photos of the baby geese following him
around right in fact, as if he were a mamma goose.
Speaker 4 (04:29):
Yeah, exactly.
Speaker 2 (04:31):
And so but that window of time where they're so
sensitive to their environment and they form these lasting attachments
only lasts about forty eight hours, and then afterwards they don't.
They're not sensitive to their environment in the same way.
They're not learning from their environment in the same way.
And that window of time Conrad Lorenz called it the
critical period. And since that time we've discovered literally dozens
(04:53):
of other critical periods. So there are critical periods for
rewiring the visual system, critical periods for touch, critical periods
for movement, critical periods for language. Language is probably the
one that most people are familiar with. If they try
to learn enough their language when they were older, it's
much harder and you always have an accent compared to
(05:13):
the language you learn as a child, and so neuroscientists
have known about these critical periods for a long time,
and we've had this idea that maybe the reason that
we're so bad at curing diseases of the brain, neuropsychiatric
illnesses and neurological diseases, is because by the time we
get around to correcting whatever is the underlying problem, the
(05:38):
relevant critical period.
Speaker 3 (05:39):
Has already closed.
Speaker 2 (05:41):
And so the classic example of this is if you
are born with bilateral cataracts in your eyes and you
don't have them removed by the time you're aged five
or so, then you will be blind forever because even
if you remove the cataracts, wants the ability of the
visual part of the brain to adapt to the corrected
visual environment. Once the critical period has closed, it can't
(06:04):
adapt again, and so even though the impediment is removed,
the brain can respond to it, and so you're blind forever.
And so we have been looking, probably for the last
one hundred years or so for ways to reopen critical periods,
with the idea that if we could reopen them, we
could potentially cure or do a better job of correcting
(06:27):
some of these impairments later in life.
Speaker 1 (06:29):
So in this Nature paper, that you published last year.
You write, it's tempting to speculate that the altered state
of consciousness shared by all psychedelics reflects the subjective experience
of reopening critical periods. Let me say, first of all,
I like, it's tempting to speculate. It's like, you're not
(06:50):
even speculating.
Speaker 5 (06:51):
It's more speculative than speculating, right, Like, we're not going
to speculate, but we're tempted to speculate. So and I
appreciate that, right, Like, this is clearly speculative, it's based
on research and mice. But why are you tempted to
speculate that psychedelics may reopen critical periods in the brain?
Speaker 3 (07:09):
Right?
Speaker 2 (07:10):
So, the reason that we're tempted to speculate this is because,
you know, one of the other things that brings together
psychedelics as a group of drugs is that they all
induced this altered state of consciousness. So we discovered a
critical period in twenty nineteen for Social rewards learning. It
(07:30):
was a brand new critical period. Although you know, there
was a lot of literature from human studies suggesting that
such a critical period should exist, but it just took
doing it. In nine hundred mice to be able to
formally demonstrate it. So we did that. We showed that
there's this social critical period, and originally we showed that
MDMA was able to reopen this critical period. And we
(07:53):
thought because MDMA is characterized by having this pro social
property that makes it different from the other psychedelics in that,
you know, it's altered state of consciousness, plus you know,
cuddle puddles and empathy, right, and so we thought it's
because of that pro social property of MDMA that it's
(08:13):
able to open this social critical period. But then when
we figured out that well LSD and I began and KETYMI,
none of which are like particularly pro social, nobody's you know,
doing a thirty person cuddle puddle on I begin right,
even though they don't have this pro social property, they
are all also able.
Speaker 3 (08:32):
To open this critical period.
Speaker 2 (08:34):
And so that was our first hint that maybe the
common property is between psychedelics that accounts for this altered
state of consciousness that they all induce is the common
property of inducing critical period reopening.
Speaker 1 (08:52):
And so specifically, can you just talk a little bit
more about the specific critical period in mice that you're
looking at here, right?
Speaker 2 (09:01):
So, we're measuring something called social condition place preference, which
is just an assay to measure the ability of the
mice to learn from their social environments. And so that
ability changes over time, and as they get older, they
stop learning from their social environment. And so this developmental
(09:22):
change relates to why we think teenagers are so much
more susceptible to peer pressure than adults. We think it
relates to why you're so much more sensitive to learning
the rules of your culture when you're young, so you know,
you learn what's polite.
Speaker 1 (09:37):
So it's basically the idea is that there's a critical
there is some set of critical periods for learning social
behavior from language to norms, and that that those clothes
over the course of childhood and adolescents.
Speaker 3 (09:53):
That's right, that's right.
Speaker 2 (09:55):
And we think that that critical period, like other critical
periods like language, you know, is curtailed as you get
older because basically it's sort of expensive energe to always
be having to learn from your social environment.
Speaker 3 (10:13):
You know, I like to.
Speaker 2 (10:15):
Think back on my teenage years and you know, mostly
I'm relieved that they're over, because you know, it was
time consuming and energetically exhausting to you know, have to
care about the exact right shade of acid washed genes
that the cool kids are wearing.
Speaker 1 (10:30):
Right, and now you wear whatever acid wash genes you want, right,
that's right.
Speaker 4 (10:34):
I wear mom jeans that are acid washed.
Speaker 1 (10:39):
And so then you find that when you give psychedelics
to an old mouse, they're able to the.
Speaker 2 (10:47):
Learning that they were doing in juvenile in their juvenile
period return, so they're able to learn again like a juvenile.
Speaker 1 (10:55):
Have you tested this theory on other critical periods in
mice or on other animals?
Speaker 2 (11:01):
Yeah, So basically, as soon as we got this this result,
I reached out to every single person that I know
who works on critics periods, and I was like, do
you have a critical period that you want to try
and reopen? Because I think we might have accidentally stumbled
on the master key for unlocking critical periods, and so
we're working on it. We definitely have some collaborations going.
(11:24):
But in the meantime between sort of when we first
have this twenty nineteen paper and then this summer, there
have been some hints that other critical periods are being
reopened by say ketamine. There are two papers showing that ketamine,
if given back to back to back to back can
reopen the critical period for ocular dominance plasticity, which is
(11:47):
this visual critical period that we've learned so much about
the mechanisms about. So that's a first hint, and we
are working feverishly to see if we can reopen other
critical periods like motor learning for stroke. We're doing that
in both mice and in humans. We're working on some
language critical periods in collaboration with some of the labs.
(12:09):
So you know, the jury is still out, but there's
some other reasons to make us think that we're on
the right track with this idea about the master key.
Speaker 1 (12:20):
When you say master key in this context, in this context,
exactly what do you mean?
Speaker 2 (12:25):
So I guess what I mean is is that when
I was a graduate student, we were a little bit
in a debate with another lab that was proposing that
there would be some drug or manipulation that you could
do that could reopen all critical periods, and that you
could just give that drug and it would it would
(12:48):
it would be the master key, right and for unlocking
all of these critical periods. And at the time, I
remember being really skeptical of that idea, and I thought, well,
anything that can do that to the brain is either
going to induce amnesia, cause seizure, or disrupt the structural
integrity of the brain. And I thought that because of
(13:11):
what we knew about, you know, basically the mechanisms that
constrain critical periods to these windows of time, like like.
Speaker 1 (13:19):
You couldn't work without breaking the brain. The only way
to reopen the critical period is the master key is
like a sledgehammer that's just gonna totally break everything. So
why even bother.
Speaker 2 (13:29):
Right, And I you know, I called it the Melti
brain problem, right, And so then when we when we
started getting these results for the psychedelics, I was, I
started thinking, well, how come we're not running into the
Melty brain problem? And I think, and this is at
this point still speculative, and we're we're actively pursuing this
(13:50):
line of research. So I don't want to overstate the case.
But my hunch is that the way that we are
able to circumvent, or the way that psychedelics specifically are circumventing,
the Melty brain problem is that they are context specific.
So it's not that psychdelics are causing reopening of all
(14:12):
critical periods everywhere in the brain all at the same time.
It seems to be that they are not you know,
destroying or melting the brain, because they're only making available
for modification the subset of synapses, circuits, memories, and grams
(14:34):
that are have been recently activated, and that is why
they have this constraint of being context dependent.
Speaker 1 (14:42):
So this is this is why your thesis is they
will psychedels will be helpful when paired with interventions like therapy,
but not by themselves.
Speaker 4 (14:53):
Well, this is.
Speaker 2 (14:56):
This is the explanation we have for why the psychedelics
aren't breaking the the brain rather than I mean, basically,
the clinical data is driving this idea that in fact
the context matters, right.
Speaker 1 (15:12):
But it's a potential mechanistic explanation for that.
Speaker 2 (15:15):
Clinical well that feature, that's right, it's a mechanistic explanation
for a clinical description, which you know, I don't think
is going to be the case for every single application
that psychedelics might be used for. So, for example, I
think the critical period idea nicely explains why MDMA assisted
psychotherapy works. If we're able to demonstrate that we can
(15:37):
correct motor impairments following stroke with psychedelics paired with physical therapy,
then that'll be a nice other explanation.
Speaker 1 (15:47):
That's a huge idea. You've just dropped in the middle
of a list, by the.
Speaker 2 (15:52):
Way, right, So, by the way, that's also quite quite speculative.
Speaker 1 (16:00):
After the break, how gool plans to test this hypothesis
that psychedelics may help patients recovering from strokes. Let's just
talk about how we get from this sort of you know,
(16:23):
seems like psychedelics reopen one critical period in mice to like,
can this idea be helpful in humans?
Speaker 4 (16:31):
Right?
Speaker 1 (16:33):
You must know the aphorism mice lie and primates exaggerate.
I was thinking of that one.
Speaker 2 (16:39):
I mean, I think that a little bit of why
it's so hard to translate this stuff from mouse studies
to human studies so far is that mostly what they've
been used for is non psychiatric disease, and so it's
really sort of impossible to measure or to recapitulate all
(17:00):
of the features of a psychiatric disease.
Speaker 3 (17:03):
In a mouse. Right, Like if.
Speaker 2 (17:04):
PTSD is mostly in humans and females is caused by
you can't really model rape in a mouse, right, And
so there are all these other features of the illness
that you know, you can try and approximate by fear learning,
but you're not really going to capture the salient elements.
And so this is kind of why I think an
(17:26):
important test case of this idea of the master key
is to switch away from neuropsychiatric disease and move into
neurological disease, because then you know, we can explicitly test
this learning model. Right if we switch to a neurological
disease like stroke, and we're able to show that if
(17:47):
we give psychedelics and pair it with physical therapy, we
are able to restore motor learning. But if we give
psychedelics and then just send them on home without any
additional physical therapy, then nothing really is going to happen.
That I think would be an explicit test of this
idea that what the mechanism at work here is about
(18:09):
learning and memory rather than a magic bill that corrects
an underlying biochemical imbalance.
Speaker 1 (18:15):
Well, yes, I mean that's the side of it, addressing
this debate that you're involved in, but also going on
there presumably if you're able to do this test in
stroke patients, is if psychedelics plus physical therapy after a
stroke leads to better recovery than physical therapy alone. That's great.
I mean, I don't even care about the mechanism at
(18:35):
that point, right, Like, is somebody going to do a
phase one safety trial soon? Like is somebody going to
give stroke patients psychedelics?
Speaker 4 (18:44):
We are, we are working on it.
Speaker 2 (18:46):
Right after this call, I have a meeting to try
and secure funding to make that happen. So we are
on it, and we are actually doing it in parallel
with mouth studies for mechanism. And you know, I understand
why people are so much more jazzed about you know
the clinical outcomes and you know the real world impacts
of these things. But I have to say, I think
(19:08):
mechanism should not be underestimated as an important way of
understanding this, because we never would have even come up
with this idea of thinking about stroke if we hadn't
thought of the mechanism. Right, So, if we the mechanism
is what is leading us to speculate, if this mechanism
is true, then these other diseases should respond in this
(19:30):
predictable way.
Speaker 1 (19:31):
There was a better way I could have framed that,
And I apologize. I mean, what I really mean is, yes,
it's it's useful and big to learn the mechanism. But
like helping stroke patients get better is also a huge deal.
Would perhaps be diplomatic way to say that.
Speaker 2 (19:48):
I mean, I don't mind the undiplomatic way, because that's
I've been dealing with this right from the beginning.
Speaker 4 (19:53):
Right.
Speaker 2 (19:53):
So, the first time I presented this critical period idea
at a meeting, it was in Portugal, and you know,
the room was full of people who were already doing
clinical trials for psilocybin for depression and MDMA for PTSD,
and they were already very much invested in the idea
that it was going to work based on some underground
(20:14):
therapists results and anecdotal reports, some of their you know,
pilot studies, and they were like, why do we need mechanism?
Speaker 4 (20:22):
Who cares?
Speaker 2 (20:23):
We know it's going to work, and going backwards to
look in mice seems silly.
Speaker 4 (20:27):
We know it's going to work. It's just the way
to die.
Speaker 2 (20:30):
And I said at that time it was like, mechanism matters,
and there are going to be a million different ways
that we might fail if we don't understand exactly how
these drugs are working. And basically that prediction ended up
being true because the two people who were represented in
that room were on the one side, the people arguing for,
you know, let's just use psilocybin like a next generation SSRI,
(20:53):
and their trial failed. And then the other half of
the room where people who were saying, no, we need
to pair it with psychotherapy, and their trial was successful.
And our mechanism, we think explains the difference between them.
Speaker 1 (21:06):
Is there an animal model you can use is to
test your hypothesis that in stroke patients psychedelics plus physical
therapy would work better than physical therapy alone.
Speaker 2 (21:20):
Yes, So basically, one of the people I reached out
to when you know, we first got this critical period
result for all of the psychedelics. We're two neurologists at
John Hopkins, so Steve Zeiler and John Krackauer, and Steve
Zyler especially had been working on developing a mouse model
of stroke. And what he has shown is that just
(21:43):
like in human patients with stroke, right after the stroke,
there is a critical period that gets reopened and some
amount of physical therapy is able to restore function, but
that that is time limited. So in my you know,
within seven days after the stroke, they're no longer able
to learn. In humans that's a little bit longer. So
(22:04):
you know, in humans. After your stroke, you're able to
benefit from therap physical therapy for about two months. At
about three months it goes away, and that window of time,
you know, it's closure. And people have thought about, well,
you know, nobody has dreamed big that we might be
able to reopen it. But people have tried to do
other manipulations that might keep it open longer, you know,
(22:26):
by enriching the environment, by you know, giving them SSRIs,
and none of those things have worked.
Speaker 1 (22:32):
It's the injury of the stroke itself is inducing the
brain to reopen the critical period that has been closed
since childhood, and that allows people to whatever, try and
relearn language, try and relearn motor skills whatever they have
lost in the stroke. Obviously not always successfully.
Speaker 3 (22:50):
That's right.
Speaker 2 (22:50):
And basically until this this psychedelic idea came around, the
most effective way to reopen the critical period for motor
learning after stroke was to give another stroke, which is
not you know, very therapeutically viable, right Like, nobody wants
to hear their stroke with another stroke. So this idea
is testable and we are in parallel testing it in
(23:14):
collaboration with the Xylor lab. This is not a social
critical period this is a motor critical period. So let's
test the idea that in this context what matters is
the motor learning or the practicing a motor task, not
the social And so we're testing that and combining with
different psychedelics, but we're comparing all of those different conditions
(23:34):
to test this idea in mice, and then in parallel,
we will do the study to look at you know,
trying to reopen in humans.
Speaker 1 (23:43):
And so the mouse study is underway now, and you're
trying to get funding for the human study, that's right.
And then once you have the money, then you go
to the institutional review board and say can we do this?
Speaker 2 (23:55):
Yeah, you know, everything's queued up and wow, you know,
everything is basically ready to go.
Speaker 4 (24:01):
We just need the money.
Speaker 1 (24:03):
So non trivial, but it's a lot probably surmountable.
Speaker 4 (24:08):
Yeah, yeah, I mean it's a lot of money.
Speaker 2 (24:10):
We're asking for a million dollars to run, you know,
a safety trial and about twenty people. And then if
that phase one trial goes well. The way the trial
is designed is that it will allow us to collect
just a little bit of in addition to how well
this patient population, right, because these are older people who
have other medical issues, so we just want to be
(24:32):
double sure that you know, these drugs are safe in
this population. But the way we've designed the trial is
it'll give us some hints about efficacy, so we'll test,
you know, a little bit of you know, their ability
to recover motor function. And the most important thing about
the human trial and the way that I the reason
that I paired up with Steve and John is because
they have actually developed a sort of gamified virtual reality
(24:56):
context for delivering this physical therapy. It's a virtual reality
kind of room, and the cameras track the person's body
position in space, and as they move their arm around,
a dolphin on a screen moves around, and it's sort
of a fun way to get people to practice moving.
But it's also a little bit more play like, which
(25:19):
is more the way that we learn during our childhood.
So there's this shift in the way we learn between
childhood and adulthood from exploratory learning to sort of goal
directed exploitatory learning, and so we want to kind of
mimic that as much as possible, to make it fun
(25:39):
and to make it not be goal directed.
Speaker 1 (25:42):
They're already doing that sort of psychedelic adjacent sounding thing
where your arm is a dolphin and you're playing. They're
doing that without psychedelics, and you're like, let's definitely add
some psychedelics to that. I mean, is that not to
be glib about it, but they're already doing that without psychedelics.
Speaker 4 (25:58):
That's right.
Speaker 2 (25:59):
So they have developed that whole paradigm to test the
efficacy of that sort of gamified environment compare to standard
of care, because standard of care is really mostly just
teaching patients how to say the other hand, to zip
their zipper and brush their hand. It's really compensatory, not
(26:22):
trying to bring back the lost motor function. And so
they've done head to head studies of the virtual reality
game version versus standard of care during that open state,
of the normal open state of the critical beers, so
right after the stroke. They've shown that there's better outcomes
(26:43):
if they use this gamified version. And so now we're saying, okay,
let's take all those people who didn't get the optimal
therapy right after their stroke, people who had a stroke
a year ago, and go back and see if we
can reopen this critical period and then give them what
we think is the better therapy in terms of this
virtual reality.
Speaker 1 (27:08):
We'll be back in a minute with the lightning round. Okay,
let's finish with the lightning round.
Speaker 4 (27:24):
Okay.
Speaker 1 (27:25):
What's your biggest professional disagreement with your mother.
Speaker 4 (27:30):
Whether psychedelics can cure allergies?
Speaker 1 (27:34):
Go on.
Speaker 2 (27:35):
Okay, Well, so my mother is an allergy and immunologist clinician.
She's retired now, but you know, I've told her this
crazy idea that we had about psychedelics and she was like, no,
that's not how it works. And the idea is based
on the fact that, you know, there's some evidence to
support the notion that allergy happens because you know, the
(27:58):
immune system, the part of the immune system that's normally
supposed to fight off parasitic infections, is being underutilized by
our modern diets, which are put more parasite free than
our evolutionary history, and so it's sort of left jobless
and it's looking for a job. And my idea is that, well,
(28:19):
maybe the brain is assigning the job and saying that
dog barked at you, that's scary, that's the threat to
go after that immune system, and that if that's a
learned association that the brain decided that it could unlearn
it too.
Speaker 3 (28:34):
By reopening this critical period.
Speaker 4 (28:35):
It's totally speculative.
Speaker 2 (28:36):
I have to say, like, I don't believe it enough
where I'm like out, you know, doing psychedelics and snuggling
up to a horse.
Speaker 4 (28:43):
I would love to cure my horse allergies. But I don't.
I don't believe it enough to go for it.
Speaker 3 (28:48):
I think it's a testable hypothesis that we should study.
Speaker 1 (28:51):
And your and your mom believes it even less than
you do.
Speaker 4 (28:54):
That's right.
Speaker 1 (28:55):
Yes, what's your favorite portrayal of a psychedelics of a
psychedelic experience in you know, in whatever, in a book,
in a movie, in music.
Speaker 2 (29:07):
I really still have a soft spot in my heart
for the Huxley description of him staring at a chair,
because you know, as a scientist, I have to say
that one really resonates. Like I'm not a religious person,
mystical experiences, that stuff doesn't really resonate with me. But
he's staring at a chair and sort of being mesmerized
(29:31):
by the you know, asymptotic distribution of chair molecules the
further away you get from the chair, and then the
Huxley molecules the further and then you know, the two
of them sitting on each other and suddenly they're inert
they're intermixed, and Huxley is the chair.
Speaker 4 (29:47):
I mean that that resonates.
Speaker 1 (29:48):
But have you ever taken psychedelics for work?
Speaker 4 (29:54):
I don't know.
Speaker 2 (29:55):
Yeah, I don't really want to talk about that or
answer that question.
Speaker 1 (30:00):
Mine totally reasonable. Do you have any advice for people
who are considering taking psychedelics recreationally.
Speaker 2 (30:08):
Yeah, it would say that, you know, these are powerful
medicines and that we should honor and respect their power,
and that they're doing something. If we're right, they're doing
something very big to the brain, and that this transformation
should not be taken lightly. And you know, I would
also emphasize that our studies suggest that once you reopen
(30:31):
these critical periods, especially with psilocybin, MDMA and LSD, they
stay open for several weeks after the acute effects of
the drug wear off, and so you're gonna be in
a in a sort of vulnerable state that's reminiscent of childhood.
And I would say be very very cautious about who
(30:51):
you expose yourself to during that period. You know, if
you're in a traumatic relationship, it's probably a good idea
to stay away from your traumatizer for a couple of
weeks after you've taken the drug, you know. I think
that we can learn a lot from the history of
these drugs.
Speaker 3 (31:10):
You know.
Speaker 2 (31:10):
Charles Manson is a good example of somebody who gave
psychedelics to people and then used it to, you know,
when they were in this vulnerable state, which presumably lasted
for a long time, to indoctrinate them into his way
of thinking, and turned a bunch of hippies into killers
who were going to, you know, induce helter skelter to
(31:31):
save the world. This is the sort of awesome power
of these drugs that we need to be very mindful
of and not treat them like little toys.
Speaker 1 (31:43):
Anything else, anything else we should talk about. I know
you've got to go. I don't want to keep you,
but if there's anything else you want to say.
Speaker 2 (31:49):
Please, I think we covered a lot, super fun. Thank
you so much, any.
Speaker 4 (31:56):
Thanks one million dollars.
Speaker 1 (32:06):
Gool Dolan is a professor of psychology and science at
UC Berkeley. Today's show was produced by Gabriel Hunter Cheng.
It was edited by Lyddy Jean Kott and engineered by
Sarah Bruguier. You can email us at problem at Pushkin
dot Fm. I'm Jacob Goldstein and we'll be back next
week with another episode of What's Your Problem.
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