ANDREW HUBERMAN: Welcome to
the Huberman Lab podcast, where we discuss science
and science-based tools for everyday life. [MUSIC PLAYING] I'm Andrew Huberman,
and I'm a professor of neurobiology
and ophthalmology at Stanford School of Medicine. Today, my guest is Dr.
Robin Carhart-Harris. Dr. Carhart-Harris is a
distinguished professor of neurology and psychiatry
at the University of California, San Francisco. He is one of the
leading researchers in the field of psychedelics
and how they change neural circuitry in the brain. His laboratory is responsible
for understanding, for instance, how
psilocybin, also sometimes referred to as magic
mushrooms change neural circuitry in the
brain, such that new ideas and new forms of learning occur. His laboratory is also
responsible for carrying out various clinical
trials, some of which have demonstrated that
appropriate dosages of psilocybin can alleviate
major depression in more than 67% of people
that take the drug. Now, this is not to say
that everybody should take psilocybin, and today's
discussion describes both the clinical trials and why
treatments with psychedelics in some cases work
and in some cases do not work in order to
treat major depression. As well as discussions around
psilocybin, lysogenic acid diethylamide,
sometimes also referred to as LSD, as well as DMT. And how these change the brain,
and how those brain changes can relate to changes
in mental health, as it relates to depression and
other psychiatric challenges, as well as how psychedelics
are being applied in order to change neural
circuitry for sake of expanding different aspects
of the human mind, including creativity,
intelligence, and much more. During today's discussion
Dr. Carhart-Harris teaches us about the history of
the study of psychedelics, as well as how the legislature,
that is the laws surrounding psychedelics, are evolving
in the United States and elsewhere for the
use of psychedelics to treat psychiatric challenges. By the end of
today's discussion, you will have a
thorough understanding of how psychedelics work. Both in the short-term during
the actual journey or trip. In fact, much of my discussion
today with Dr. Carhart-Harris talks about the
different aspects of the psychedelic
journey and how those relate to therapeutic outcomes. And, of course, by the
end of today's discussion, you will also understand
the long-term effects of psychedelics, that
is, how they can actually rewire the brain. Before we begin, I'd
like to emphasize that this podcast is separate
from my teaching and research roles at Stanford. It is, however, part
of my desire and effort to bring zero cost to
consumer information about science and
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hubermanlab.com/tour and use the code "Huberman"
to access tickets. I hope to see you there. And now for my discussion
with Dr. Robin Carhart-Harris. Dr. Carhart-Harris, welcome. I've been wanting to talk
to you for a long time. I certainly have known who
you are for quite a while, because I place you in
this very small but very special and important
category of researchers who has been pioneering
the use of psychedelics for the treatment of
specific clinical conditions, and really carrying the
torch for, essentially, the entire field. So I want to start with
a voice of gratitude and say thank you for doing
this incredibly important work. Could you tell us a little bit
about what psychedelics are? In fact, I'm curious as to
how the name psychedelic ever came to be. ROBIN CARHART-HARRIS: Mhm. ANDREW HUBERMAN: And what
you think they potentially reveal about the
workings of the brain. And then we'll talk about
the clinical applications. ROBIN CARHART-HARRIS: Sure. Well, even that one
is kind of hot one, because opinions differ on
how to define psychedelic. But perhaps, a
good starting place is to start with the etymology,
where did the word come from? And it was a Brit
excommunicated living in Canada Humphry Osmond
who was due to present a paper at a National
Academy of Sciences meeting on psychotomimetics-- drugs that mimic aspects of
psychosis in their action. And certain drugs
like mescaline-- let's see, 1956-- and
LSD were on the bill. And he felt
dissatisfied with them being under this category
of psychotomimetics, and felt that the signature
psychological effects of these compounds
went beyond just mimicking psychotic symptoms. And so he wanted to
find a more apt term to speak to, in a sense,
the principal component of their action. And he jotted down a few
different possibilities about a dozen or so, I think. And one of them was
psychodelic, actually it started as and ended
up being psychedelic. And he had a correspondence
going on with another Brit also living in the US,
Aldous Huxley, where they were playing
with some terms to refer to these compounds. And in the end, Osmond
won with psychedelic, and he had this little ditty of,
to fathom hell or soar angelic, just take a pinch
of psychedelic. That's where you put
the disclaimer in. And so what does that mean? It's two ancient Greek words
psyche, means the human mind or if we're being actually
true to the ancient Greek it means soul. And then the other component
means to make clear or to make visible or to
make manifest or to reveal. So all of those work. And it's a neologism. It's a made up word. But it does have that
ancient Greek origin. And it's speaking
to this principle that these compounds reveal
aspects of the psyche, of the human mind, the soul
that are ordinarily not entirely visible. And so that's the etymology,
and it's wonderfully poetic. But I happen to think
it's also very accurate. It's a useful term,
because it's sort of, you might say
valence nonspecific. It doesn't say, you're
going to have a great time or that you're going to go mad. It's more that-- it reveals a
psyche, and it could be hellish but it could be heavenly. So that's the etymology and
also a bit of the psychology. And sort of pointing
to the phenomenology, the subjective experience. But there's also a
pharmacology here. And quite recently, there was
put out a consensus statement about psychedelics
that's really referring to what we call the classic
psychedelics to say that these are all compounds that work
on a particular receptor in the brain, the
serotonin 2A receptor. And that's another way that we
could define these compounds. I said this one's a little
hot, because I'm of the view that while the pharmacology
is really useful, how the drugs work chemically, you
can't avoid the phenomenology. And if we're true
to the etymology, where the term came from,
then we must recognize, and we cannot neglect the
subjective experience. ANDREW HUBERMAN: Thank you
for that beautiful description of what brought us
to today in terms of using the word psychedelics. And now, it's thrown
around all the time. ROBIN CARHART-HARRIS: Yeah. Too much. ANDREW HUBERMAN: Yeah. Too much. And I'm guessing--
well, not guessing. I'm certain that it's also used
to describe many compounds that don't touch the 5-HT2A,
the serotonin 2A receptor. So there is a broader
categorization by most people. And it'll be interesting to
see where all the nomenclature and naming goes. For the time being, I'd
love for you to tell us a bit more about this idea
that psychedelics, however one defines them, can reveal
something about the mind that can't be revealed otherwise. Are you talking about
the subconscious? I mean, psychologists and most
famously, Freud but also Jung and also neuroscientists, I
think, think about subconscious processing. I think, perhaps, the
most salient example for me that's outside the
realm of anything psychedelic would be blindsight. This phenomenon that you take
people that are blind but still have some connectivity
in their brain and you present
them a board with-- or a computer screen with
different number of dots on each side and you
say how many dots are on each side of the screen,
and they say, what do you mean? I can't see the screen. I'm blind. And you say, well, just guess. And their guess rate
is accurate far more than chance would predict. ROBIN CARHART-HARRIS: Mhm. ANDREW HUBERMAN: So they
have so-called blindsight, and people have said, well,
this is the subconscious revealing itself. There's no psychedelic
drug involved. But what you're describing is
a pharmacologic-induced state that reveals something that
normally should we assume is masked or that we
are oblivious to-- even though it's
expressing itself. What does it mean
for these drugs to be revealing something about
the workings of the mind that would not be obvious
to us, otherwise. ROBIN CARHART-HARRIS: Yeah. So the example of blindsight is
interesting but it's different. Blindsight would be referring to
non-conscious processing, maybe implicit processing. So stuff going on in
the mind in perception in a sense that is
below the threshold of conscious awareness. But yet is influencing you. So it's sort-- it's kind of
related, but it's different. So in depth, psychology,
psychoanalysis, psychodynamic, psychology, Sigmund Freud,
Carl Jung, and so on. We talk about the unconscious. And there, it's more
about the kind of blood and guts of the human
condition, the human nature-- both the personal unconscious. So things that
you might not want to necessarily be conscious
of, because it's painful. So that's the repression
aspect pushing it out of conscious awareness. ANDREW HUBERMAN: Repressed
memories in particular? ROBIN CARHART-HARRIS: Yeah. Like traumatic memories,
difficult relationships. It could be complex
trauma, not necessarily just a specific index trauma,
but a series of trauma. And then you have the
collective unconscious, which was really Carl
Jung's contribution to say that there's a
transpersonal quality to the unconscious. There's aspects about humans,
not just this individual human. There's aspects to our
minds, our psyches that are not fully available
to conscious awareness, but can come up
in certain states. Psychoanalysis went crazy for
dreaming as their royal road to a knowledge of
the unconscious. That was Freud. But we now with
psychedelics, and this was what drew me into the area. Was discovering
literature that was speaking to this particular
action, the psychedelic action. And was saying that
when these drugs-- like LSD, psilocybin
found in magic mushrooms, when they're used
in psychotherapy, material comes up that may be
may have been repressed that is of therapeutic value
and awareness and insight of this material
seems to catalyze the therapeutic process with
strong emotional release. These cathartic
experiences and insights. Whether they're insights
that are personal or whether they're
transpersonal. But for me, this is really
where the meat of it is with psychedelics and classic
psychedelics, in particular. The likes of compounds
like LSD and psilocybin. I would say that if it
wasn't for this action by classic psychedelics,
we wouldn't be so interested in psychedelics. I think, if we only had
compounds like ketamine, MDMA cannabis, that could be
said, broadly speaking, to be psychedelic-like. I don't think it
necessarily would have captured the world's
attention as psychedelics are right now. I actually think it's
a major gap to fill. Is this principal action of
the classic psychedelics. What does this mean
that I'm referring to? Psyche-revealing. What is that? And I suppose where
I'm going with this is, what is that in terms
of the biology as well? What's going on in
the brain and the body when people become
aware of things that previously they
weren't fully aware of. ANDREW HUBERMAN: I'd
like to talk about some of the clinical trials that
you've been involved with. In particular,
looking at psilocybin. As you mentioned, the principal
hallucinatory psychedelic agent in magic mushrooms. I'd like to start with a kind
of nuts and bolts question just so that everyone's
on the same page. I've read the papers
that you've published and that others have
published in this area. And typically, the dosages
used in these trials are 25 milligrams of psilocybin. And we talk about
one recent trial, in particular, that
compared 25 to 10 milligrams to more frequent use
of very small amounts. 1 milligram over 3
weeks, for instance. However, when people talk
about magic mushrooms, they often talk about gram
doses of the mushroom, because I'm assuming that
they contain milligram dosages of psilocybin. Here, we're not encouraging
use of any kind. These are clinical trials. But for clarity of
understanding, what is the conversion, typically? Like 1 gram of
magic mushrooms will contain how many milligrams
of psilocybin on average. Because what I'm
trying to do here is calibrate people to
this idea of microdosing versus macrodosing. And that's fairly
straightforward to do with respect to
the clinical trials. But then in a lot of the
lay discussion around this, you hear about heroic
doses versus microdoses. And so I think there's
a lot of confusion. So if you would,
educate us on this idea of what's a microdose. And perhaps, also how many
milligrams of psilocybin are contained in a gram of quote
unquote, "magic mushrooms?" ROBIN CARHART-HARRIS: Sure. Well, a microdose is
neither of these are that. Simple. But they're fun. It's a fun challenge. But microdose, one
definition is that it's a dose of typically a
classic psychedelic like LSD or psilocybin that has some
perceptible psychedelic effects. It doesn't put you into a
noticeable altered state of consciousness that
feels like you're tripping. And if that was LSD, it
looks as though the threshold is around about, let's
see, 10, 11, 12 micrograms. ANDREW HUBERMAN: Micrograms. ROBIN CARHART-HARRIS:
Micrograms. ANDREW HUBERMAN: Want
to be very clear here. Micrograms. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: So
10 micrograms of LSD, are you saying will not induce
visual hallucinations in most people? ROBIN CARHART-HARRIS: So
that's threshold level. That's about the level that
some people who are sensitive could feel it. But if you were to talk
to the microdosing gurus, they might say that that's
the ballpark for an LSD dose that you would
consider a micro dose, and then you would
take semi-regularly. It's typically
something like one day on, one day off or one
day on, two days off. This kind of thing. There's different protocols. And yeah. So some like Jim Fadiman-- one of the popularizers
of microdosing, I think would say that a true microdose
should be sub-perceptible. You shouldn't feel
it, yet the assumption is it's going to change you
in some way on a kind of trait level more than a state
level, and maybe behaviorally. And the typical story goes,
it will improve well-being. And maybe, maybe,
it could improve certain aspects
of cognition, say, related to creative thinking. I emphasize the maybe
there because that's another angle with microdosing. We're waiting for some
compelling evidence. As things stand
right now, I'd say, we lack that
compelling evidence. There's some suggestive stuff,
but often the study designs aren't that strong. It's really hard to do a
study with microdosing, because you need to have
permission to give people a microdose that for
practical reasons, they would go home with,
otherwise, you're requiring them to be in the lab, say
three times a week for x number of weeks to meet the criteria
of a course of microdosing, which might be two or three
times a week for say, a month. And that's a hard thing
to do in a lab study. It's expensive. You'd need to do that
against a suitable control, so a placebo control. And there is a study
that's been done in New Zealand that has some
interesting preliminary data that did-- I think did the design right. But it hasn't been
published yet. I've seen some positive
findings presented around improvements in mood. But it's a bit early to
get too excited about that. It needs to go through
peer review and all that. But as things stand, the
evidence is pretty thin. And we have to be
honest about that. We did quite a creative study
with my colleagues at Imperial. The guy leading that, Balazs
Szigeti, a Hungarian chap, did a really creative design. Very much his brainchild. He instructed people to
do their own blinding, their own
placebo-controlled blinding of their own microdosing. So this was a classic
citizen science study like do it yourself science
where they would get their LSD tabs and chop them up, put
them into gel capsules, opaque, and have other capsules
that are the placebos that they just close empty capsule. And then there was a whole
barcode scan technique so that you kind
of shuffle them up. But they've got the
barcode in, the QR code. So you can break
the code later on, but once you've
shuffled them up, you no longer know which
ones had the microdosing and which ones are empty. ANDREW HUBERMAN: Was this LSD? ROBIN CARHART-HARRIS:
This was LSD. Also tried it with
mushrooms, but the issues with the mushrooms was
people would burp sometimes. They'd belch. And then they'd have
this mushroom taste. So then he instructed
people to get some non-psychoactive
mushroom material to put in. So it's really-- ANDREW HUBERMAN:
Not an easy study. ROBIN CARHART-HARRIS:
--not an easy study. And it was-- I love
that kind of science. Real creative first
mover kind of science. And the results
were fascinating, because the short story is
that the microdosing didn't compellingly beat the placebo. ANDREW HUBERMAN: It did not. ROBIN CARHART-HARRIS: It didn't. And he controlled,
because he asked. He controlled for expectancy. So people's positive expectancy,
which is, in a sense, the vehicle that carries
the placebo response. It's why you have a placebo. Is that positive expectancy
can drive a therapeutic effect to a large extent. So you measured that
pre-trial and then used it to correct for the response. And how did it work? Those who got a
placebo but thought they got a microdose
did as well as those who thought they got a microdose
and did get a microdose. So it was the bigger effect-- the majority of the
effect was in thinking that you got a microdose. So in a sense, it was a victory
for the power of the placebo response. And it's created all
sorts of controversy. People don't want to believe
it, that kind of thing. But that's the beauty
of science, isn't it? That science is not about
what you want to believe. That right there is
the beauty of science. ANDREW HUBERMAN: I
love that experiment. Kudos to them. I'm not going to attempt to
say his last name correctly. ROBIN CARHART-HARRIS: I tried. Yeah. Probably you made a mess of it-- ANDREW HUBERMAN: No. No. I think you got it. You were involved in
a clinical trial that was published last
year comparing 25 milligrams of psilocybin
to 10 milligrams of psilocybin to a drug called escitalopram. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Yeah. ROBIN CARHART-HARRIS: Lexapro. Yeah. ANDREW HUBERMAN: Lexapro? ROBIN CARHART-HARRIS: Mhm. ANDREW HUBERMAN: And this 1
milligram over a 3-week dosage. I'm wanting to discuss the
results of that study a bit and some of the other
trials that you've done involving psilocybin
for depression, the treatment of depression. Could we calibrate ourselves? 25 milligrams of
psilocybin, is that what-- it's going to be a
perceptible dose presumably. Hallucinations and all that. And is that what
one would find in-- I'm guessing here,
if I'm accurate, this does not mean that
I have experience here. But 2 grams of mushrooms? ROBIN CARHART-HARRIS: It's
more than that we think. Yeah. Sorry. I missed that-- ANDREW HUBERMAN: No, no. ROBIN CARHART-HARRIS:
I missed that one. Went off on a tangent. But yeah. 25 milligrams of
psilocybin would be-- we don't know,
and it's important that I say that because
I wouldn't want people to hear my answer
here, and then use it to calibrate their
own dosing of mushrooms and get it way off. So it's guesswork. And I would love to see someone
do a proper study on it. And look at the
psilocybin content in a given mass of psilocybin
mushrooms, magic mushrooms. But to my knowledge, that
hasn't really been done. Someone like Paul Stamets would
give a better answer here. But I think the percentage
within the mushroom mass is-- of psilocybin in the
mushroom mass and psilocin which is the metabolite
of psilocybin is something in the 1%, a
little bit higher, maybe, range. ANDREW HUBERMAN: OK. So 1 gram, 1000 milligrams
of magic mushroom would contain about 10
milligrams of psilocybin. Is that right? ROBIN CARHART-HARRIS:
Broadly speaking, yeah. ANDREW HUBERMAN: OK. Great. That helps calibrate. And I think, again, just
allows the layperson to understand a
bit more of where we're headed with
these psilocybin trials and the results. So we don't have to
restrict our discussion to just that I clinical trial. But if we include that
one and compare it to some of the other
trials that you've done, I mean, your laboratory
is seeing phenomenal-- in my opinion,
phenomenal results in the treatment of, otherwise,
intractable depression, major depression, which so
many people suffer from. From two-- I suppose
there two sessions of using psilocybin in these
ranges of 10 to 25 milligrams. Do I have that correct? ROBIN CARHART-HARRIS: Yes. ANDREW HUBERMAN: OK. Could we talk a little bit
about what people typically experience during
those sessions that allows this phenomenal
transformation of mood and state and trait as well? And I'm especially
interested in whether or not it is the experience
during those sessions that is the trigger that's necessary
for the transformation from a depressed to a
non-depressed state. Because the impulse
is to think it is. That what one thinks and
sees and hallucinates is-- and hears is so vital. But of course, these drugs can
create neuroplasticity changes in our neural wiring, presumably
for long periods of time. So what are your thoughts
on the experience itself? And maybe for those who have
not done these compounds before, you could explain a
little bit about what's typical for people,
and what you think is leading to that incredible
positive and pervasive change in mood, state, and trait. ROBIN CARHART-HARRIS: I would
say that it's more than impulse that is leading us to think that
the experience is important. It's really data and
converging evidence now. So independent teams,
independent studies are converging on the magnitude
of certain kinds of experience rated, yes, with
subjective rating scales is predicting
therapeutic outcomes. Pretty strongly
and very reliably. And so that's guiding us. Now, could you say, well,
maybe those experiences are some kind of epiphenomenon
of say, a central brain action? Well, absolutely. But then all experience
are epiphenomenon by that principle. And yet we care
about it, you know? And it matters to us and
in our human relations with each other. So I think it does
matter to a human being when they're in say, a
psilocybin therapy session, and as the drug effects
begin to come on and the body starts to feel
a little strange and tingly and there's some
initial anxiety. And then in their
mind's eye, they start to notice patterns
and maybe colors and then, maybe, those patterns
deepen and they're dynamic and they have this
fascinating organic quality. ANDREW HUBERMAN: Are they-- patients in your studies
typically using an eye mask? ROBIN CARHART-HARRIS: Yes. ANDREW HUBERMAN: So
they're in the eye mask? So eyes closed? ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: That's why
you said mind's eye as opposed to looking out into
the clinical setting. ROBIN CARHART-HARRIS: Yes. And that's one of
the major differences to psychedelic therapy
versus taking a psychedelic. Is you shut your eyes. And it's a world away
from taking a psychedelic. Yeah. A rave or something. In a sense, good luck with that. But in psychedelic
therapy, yeah. It's settled conditions. There's music playing. And what I'm describing here
is very much the default. There's actually very
little variability between the different
sites that have done this work on these conditions. Typically, it's two people. Ideally, mental health
professionals, at least one who's a psychiatrist or
a clinical psychologist or some other kind of
psychotherapist or psychiatric nurse. But ideally, two who
meet those criteria with a individual who's ingested
the drug and music playing throughout. A kind of runway into taking
the drug and then throughout, so there's continuity. ANDREW HUBERMAN: They're music
with lyrics or without lyrics? ROBIN CARHART-HARRIS: Without
lyrics, to begin with, and the music typically
is spacious to begin with. And then builds and
becomes atmospheric. There might be, I don't
know, some tribal drums in the distance or
something as it develops or like the sound of a
bird in the distance. A call. And then as it gets into
more stronger drug effects, the music starts
to coax emotion, and very intentionally, strings,
for example, would come in and it would be an
interesting experiment and one that we'd love to do actually
to see whether if you were to pull that out, whether the
psychedelic experience would be as emotionally intense as
it is in psychedelic therapy when you have music
there as a default. And across the board, people
should find this remarkable, because it kind of is. All of the published
studies that are now having such an impact
on psychiatry and beyond have music there as
a staple component. And we just take it as
assumption that it needs to be. I tend to share that assumption. But it's remarkable that it
hasn't been tested properly. But it's there. And if you were
to run with that, and if you had a critical
agenda, you would say, well, this is music therapy. Why are you making all this
fuss about psychedelics when it's music that's there
in all of these trials with all these fantastic findings. So there is something to that. And this will tee me
up probably to talk about psychedelic-therapy
being a combination treatment. We have a hyphen
between the two, because I share the hypothesis. The assumption that
should be tested better. There is a positive
interaction between the two. That there's a synergy
between the two. ANDREW HUBERMAN: That's why
it's psychedelic-therapy with a hyphen, just
like Carhart-Harris. ROBIN CARHART-HARRIS: OK. Yeah. ANDREW HUBERMAN: I'd like
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athleticgreens.com/huberman to get the five free travel
packs and the year supply of vitamin D3 K2. This is extremely
useful to hear because I think most people think, OK. Psychedelic. Whether or not they
have experience with psychedelics or not, get
some visual hallucinations, some auditory hallucinations,
some synesthesia, some visual auditory blending,
somatosensation, you know? Rubbing a surface and
being able to elicit the sounds in one's mind. Of course, et cetera. But so seldom do
we actually hear about the specifics of these
clinical trials in a way that, for instance, points to
music as one of the, perhaps, key variables. Now, you mentioned
that as people enter these psychedelic states,
that there's a little bit of initial anxiety. About a year and a half
ago, I had a discussion with Dr. Matthew Johnson who's
running some psilocybin trials at Johns Hopkins, as you know. And he mentioned the
critical importance, at least in his
mind, to this idea of the patient, quote
unquote, "letting go" or allowing the experience
to take them someplace mentally as opposed to
trying to constrain their sensory and
cognitive experience. I'm curious what your
reflections are on that idea. And why it might be so
valuable clinically. And this ties back to
this earlier discussion we were having about
the unconscious or about psychedelics
revealing something that's there all the time but that
we don't have access to. And again, I'm struggling
to find the right language for this, because
we don't really have a neural mechanism
like top-down inhibition or something like
that to explain how this unconscious
might be uncorked in the psychedelic experience. But to make it quite simple and
direct, how important do you think it really
is for the patient to feel like they are,
quote unquote, "letting go" and what in the
world is "letting go" in biological terms? ROBIN CARHART-HARRIS: Yeah. Yeah. Well, I think we'll
get there in terms of having the neural
correlates of the mind revealing itself to itself. The emergence of the
unconscious into consciousness or unconscious material
into conscious awareness. It's a wonderful challenge. It's a huge challenge, but
it's a challenge to embrace. And letting go very
much is, again, a staple component of
how the different teams do this work in terms of
encouraging a willingness to let go. And when we started out
doing our depression work and did that first trial,
it was the first trial of psychedelic in a formally
diagnosed depression, you know? Where that was the
target population. A depressed population. It was the first modern
study to do that. And we visited
Hopkins, friends there and were mentored on how to do
the guiding Bill Richards, Mary Cusumano. They were just so brilliant and
wise in their guidance to us as how to do the
guiding in our trial. And so this phrase of trust, let
go, be open, you'll hear a lot. I don't know who fairly it
should be attributed to, but I would attribute
it to Bill Richards. Yeah. Everything's borrowed. You probably got it
from someone else. But it's such a key principle. And it's almost like
a mantra that you're trying to instill in people. Trust, let go, be open. And those different
components where the trust is about the therapeutic
rapport that, again, this goes beyond just intuition now. We formerly measured
therapeutic rapport. We do it even with just a single
item, a visual analog scale item, a subjective rating scale
item on the morning of dosing, and we find that it's
a significant predictor of the quality of the
experience that you have under the drug in
the psychedelic therapy, and then the therapeutic
outcomes x weeks or months later. So very powerful chain
of predictive components there, but trust,
essentially, important. And again, not just to intuition
but the data pointing to that. Let go, there's a readiness
to surrender, to let go, to not resist. And we do measure that
too and see that it's predictive of response. And then the being open is
about a willingness to go there, to confront, to be inquisitive. Something that's
easier said than done. Can be terrifying. When you're dealing with a
very vulnerable population, it's probably more-- the rule then, the
exception that they're carrying some significant
adversity, life adversity or frank trauma that
they've suffered. And so that message of be
open, be willing to confront and to go there is
really powerful. And that's how it plays out. And often, there is struggle. There's something
going on that is I don't want to be feeling this. Make it stop. That can be
nightmarish at times, but it's very, very strong. And with these big doses that
we give, it's very strong. And actually, a
student that I've worked with, I think now
doing a PhD, at Harry Brouwer is working on a fantastic
project characterizing the different phases of
the psychedelic experience where the early
phase is dominated by negative emotions and
negatively-valenced feelings of anxiety and struggle. And then it's a different
story in the latter half. ANDREW HUBERMAN: Could
I ask about that? First of all, I think that's
fascinating and important to analyze the different phases
and, again, I'm delighted here because people
typically hear about a psychedelic
journey but we never really hear about the
stereotypic components of the beginning, middle,
and end of that journey. We know that there's a peak
and that there's a parachuting down and et cetera. But when you say that typically
there's an anxiety, maybe some negative valence
in the early stage, do you mean about the sensations
people are experiencing or about some prior event
that's being called to mind that they're remembering? Likewise, for the positive
phase of the psychedelic journey or trip are people-- do they still call it a trip? ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: All right. For the-- I guess,
we'll use trip. For the psychedelic trip. Are people feeling positive
about the experience like, uh. Like there's been some
sort of breakthrough or they're in a
calmer state, or is it that they tend to be
focusing on prior events that were positive. So in other words,
is there a threading through of some concept that
comes to mind for people? Maybe about an earlier trauma
or maybe about a sense of self or a sense of other forgiveness. It could be any of these things. But what do we know about the
finer details of all that? ROBIN CARHART-HARRIS: Mhm. I would say, the
initial struggle is more against the
general drug effects than pinning it on
something specific. It's more that normal
waking consciousness. We have a sense,
generally speaking, if we're well or well enough, a
sense of assuredness about what is a table here and so on. And we have that assuredness
to an extent about ourselves as well. It might be illusory,
but we have it. And what the drug's doing is
it's breaking down all of that. And it's scary as hell. And if it's a big dose,
it's just like human nature to rage against that a
bit and a bit like dying. I don't want this. It feels like I could be dying. ANDREW HUBERMAN: I
might lose my mind. ROBIN CARHART-HARRIS: Yeah. That too. ANDREW HUBERMAN:
I'd never come back. ROBIN CARHART-HARRIS:
Those two are the classics. Is oh, but I might know that
I've taken a psychedelic and I might even know a
bit about psychedelics, but I still fear that
I'm going to go mad or I know that
generally speaking, these drugs don't have
a high fertility risk. I still think I'm going to die. And it's very palpable
and that comes up. So yeah. I mean, those are
the core fears. That those two and very
reliably, that comes up. And it's really like
a basic drug action. It's dose-dependent but
it's a basic drug action that is forcing something
about the nature of the mind and the
way it's made up that makes it feel that way,
but it feels like I'm losing my mind or it feels like
I could lose my mind or that I could go insane
or that maybe I'm dying here and this is bad. Yeah. ANDREW HUBERMAN: You've
talked many times before and have done really
wonderful work looking at the changes in communication
between different brain areas while people are under the
influence of psychedelics. And I think the gestalt of those
data, correct me if I'm wrong, is that compared to the
non-psychedelic state, that under psychedelic influence. There is far more-- let's just call it
interconnectivity or communication between brain
areas that typically aren't communicating, which
probably is not surprising to people given
the subjective effects of these drugs. What is the evidence that
after the psychedelic journey is over, that some
or perhaps all of that enhanced communication
across brain areas is maintained? And if so, what role
do you feel that could play in these incredible
positive therapeutic outcomes? ROBIN CARHART-HARRIS: Yeah. So we've had some recent
findings in that direction where, yes, it's true. And picture says
a thousand words that some people might be
familiar with are these two circles project that
we did in collaboration with some researchers where
ordinarily, the communication is going on within
systems like other regions of the visual system
will be speaking mostly within the visual system. There'll be a kind of
cliquishness or a modularity to the quality of the
communication in the brain. And then the cool finding with
psilocybin was the first paper, is that the communication, yes. It transcends these modules and
becomes much more inter-modular crossing different modalities
and that effect correlated with the magnitude of
the subjective effects and then we replicated it with
LSD using different methods. And a new paper
will come out soon with DMT showing
a similar effect. It's a bit of a debate
about what regions are most implicated. But the general effect of an
increase in global functional connectivity is what we call
it or global communication in the brain. ANDREW HUBERMAN: And this
is while under the influence of these drugs. ROBIN CARHART-HARRIS:
This is under the-- ANDREW HUBERMAN: So putting
people into a brain scanner while they are under the
influence of the drug. Is that right? ROBIN CARHART-HARRIS: Yes. ANDREW HUBERMAN: That itself
must be quite an experience, given that these
scanners are small tubes. You're in a bite bar, you've
got a bite bar in your mouth. That's quite a study. ROBIN CARHART-HARRIS:
You don't always have a bite bar, at least
with the psychedelics. But yeah. You've got to keep
your head still. And you have the loud
MR scanner noise going. But because it's regular, there
aren't too many surprises. So it's actually
surprisingly tolerable. ANDREW HUBERMAN: You're
in a hospital setting. So you're not worried about
what would happen if you had a cardiac event or something. ROBIN CARHART-HARRIS: Yeah. You got professionals around,
and most people generally tolerate that setting quite
well, surprisingly well. But yeah. We do all that. And yes, we do
see the opening up of the communication across
systems in the brain. And it does speak
to intuition about the subjective experience. The different modalities might
be blending with each other. ANDREW HUBERMAN: Sorry
for interrupting, but I have to ask, is it
thought that the activation of the serotonin
2A receptors what's responsible for the increased
communication between brain areas that under
normal circumstances would not be communicated? ROBIN CARHART-HARRIS: Yes. So there's a few reasons why
some modeling work that-- computational modeling work that
first identifies where the 2A receptor is and then looks at-- models its basic effect
on neural activity. Will recapitulate the--
or recreate the effect that we see actually in
the data with the scanning. So doing the
computational modeling. You can see the same effect by
knowing where the key receptors are and then making them
do a certain thing that we know psychedelics do. ANDREW HUBERMAN: I can
imagine two possibilities. And I think it's important to
distinguish between these two. One possibility is that the
activation of this serotonin 2A receptor leads to
increased connectivity and thereby auditory and
visual hallucinations emerge, changed patterns of
thinking emerge, et cetera. That's the obvious
interpretation. But the scientist
in me has to ask, is it possible that all of
that increased connectivity is occurring, and yet that is
a distinct phenomenon layered on top of some other effect
of the psychedelic drugs impacting access to the
unconscious, hallucinations? In other words, is it the
increased connectivity that's leading to the
subjective experience, or are those two things
happening in parallel? ROBIN CARHART-HARRIS: Well,
they happen in parallel and they map to each other. But the question of
causality, what causes what, is the tricky thing
where I would suggest that the causality is circular. That they influence each other. And this gets a
bit philosophical. But it matters, because
otherwise, there's a trap that it's easy to fall
into where you're thinking that it's all about
the brain action causing the
subjective experience. And that's typically what we
do in cognitive neuroscience. It's like the first port of
call materialist approach. But one can be a materialist,
essentially, but still appreciate that circular
causality that mind also interacts with brain. And it's so hard to
pick the two apart. And there is a kind
of essential dualism where subjective experience
is a thing in and of itself. But that's not to
divorce it from what's going on the biological level. ANDREW HUBERMAN:
The reason I ask is because as I understand
it, nowadays, there's a bit of a movement within
the scientific community that studies psychedelics
to develop drugs that can, essentially, cure
or alleviate many of the symptoms of
depression or trauma that are built off our
understanding of how psychedelics like psilocybin and
here I'll throw MDMA in there, although classically not a
psychedelic, it gets lumped in. We can get back to that later. But that do not
produce hallucinations or massive changes in
subjective experience. Actually, I think this
is what initially got us into conversation
on Twitter as I had learned about this
paper published out of a group at UC Davis. That essentially
modifying psychedelics so that they have potential
therapeutic application for the treatment of
depression but zero hallucinogenic properties. And I thought, wow. This is going to be a
very controversial thing in the world, right? Because the history
of psychedelics, as you pointed out,
has been one of people accessing different modes
of thinking, feeling. Seeing things and letting go. Trust, et cetera. A therapeutic relationship. And here we have-- I don't want to say pharma
because it's not really pharma, but we have laboratories who
are trying to tease apart the activation of receptors
independent of all that subjective
experience in order to, essentially, treat
the same conditions. I'd love for you to
comment on this, where you think it might be going. And whether or not
you think that's the right or the wrong approach,
if it has any validity at all. ROBIN CARHART-HARRIS: It is
pharmas, just smaller pharma, sort of startup pharma. But-- ANDREW HUBERMAN: OK. So because pharma
would like to have drugs that can cure depression
but don't make people hallucinate. Is that correct? ROBIN CARHART-HARRIS:
Oh, they would. And patients might
and the system would love it, because
the system is used to it. It's medicine. ANDREW HUBERMAN: Right. And it doesn't give this mental
imagery of the Summer of Love in San Francisco or of
kaleidoscope eyes, right? It's more of-- ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: You
can imagine, the more-- I have to be careful
with my wording here. Those who would not be
inclined toward that might embrace a therapeutic
that is strictly effective at treating depression
with no hallucinations. ROBIN CARHART-HARRIS: Yeah. And it doesn't look like an
individual lying on a sofa crying their eyes out about
the life that they've lived. And that deep catharsis
being life-transforming. Is very different
from that model. I'm skeptical of it
for a few reasons. And one is that I
can't see the logic-- I can't see the pieces fit
in a way that's compelling. And I'm also skeptical,
because I think it could easily be wishful thinking, because
of that point that patients would like it and the
system would like it. And you got to bear
that in mind as well. So wouldn't it be
convenient if it were true and you could get the
therapeutic action without the psychedelic effects? ANDREW HUBERMAN:
Well, in a way, that's a little bit of what microdosing
seems to be designed to do. Like you said, take dosages
that are below that perceptual or awareness of some
effect threshold over a longer period of time in
an attempt to ping the circuits or alter the circuits
but not hallucinate. Not have a catharsis. ROBIN CARHART-HARRIS: So
if microdosing can do that, and it's sub-perceptible,
then microdosing isn't a psychedelic
action, because whereas the psychedelic action. When psychedelic, when defined,
means psyche revealing. You're not getting that effect. You might be getting
the pharmacology, you might be getting some
direct serotonin to a receptor agonism that could be driving
a therapeutic response, but you can get that
with SSRIs as well. And so my point is, what's new? OK. Maybe it's a bit new
and people are now developing direct 2A
agonists rather than indirect through a serotonin releaser
like the selective serotonin reuptake inhibitors,
the SSRIs like Lexapro. ANDREW HUBERMAN:
Are there any SSRIs that selectively agonize,
which folks by the way means, activate, in a good way. Agony sounds terrible. Those not informed might
think that mean that disrupt. But that can activate the
serotonin 2A receptor. Are there any drugs that will
do that are not psychedelic? I'm not aware of any,
but then again I'm not a psychopharmacologist. ROBIN CARHART-HARRIS:
Well, there are. I mean, are there any
that are licensed and used as medicines in psychiatry? I actually had this debate
recently on social media, and I couldn't see a
compelling example. I saw 2A agonists that
were used for other things. You have a compound
like Lesuride used in treating Parkinson's,
but actually it's more of a dopamine agonist. ANDREW HUBERMAN: Right. So they're always hitting
other things, right? ROBIN CARHART-HARRIS: Yeah. Yeah. ANDREW HUBERMAN:
They're always tapping other neurotransmitters-- ROBIN CARHART-HARRIS: All that
being used for other things. So is there a
selective serotonin 2A receptor
stimulator, an agonist, that isn't psychedelic, that
is therapeutic in psychiatry and the answer firmly is, no. I haven't seen it yet. Will they develop one? Well, for patients
sake, I hope so. Because it would be great. Let's wait and see. If they do, I doubt
it'll be psychedelic and I doubt it would have much
to do with psychedelic therapy. And it would be much more
like the system we're used to of chronic pharmacotherapy. Take your drug every day. Let's hope they find it and
it works for patients sake. But as things stand right
now, I'm a little skeptical. Now, some of the
findings that are being seen that are
really exciting, fantastic work being done, showing
things like increases in the communication
components of neurons, dendritic growth, spine
growth, synaptic spine growth. ANDREW HUBERMAN: Yeah,
by the way, folks, just I'll interrupt for
not necessarily spine-- not the cerebral
column but spines are these little
tiny twigs with bulbs on the end of neurons that
allow for communication points between neurons. So neuroplasticity
is often associated with growth of
dendrites and spines and so forth, which is
what Robin's referring to. That reminds me, and I
just want to make sure that we close the hatch
on the earlier answer, because I interrupted you. Is the increased
connectivity between-- or communication
between brain areas that's observed while people
are under the influence of the psychedelic
also observed later after the effects of
the drug wear off? ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN:
And then I'll just throw in another question there,
because we're on to this topic now. To what extent do we think that
neuroplasticity, structural changes in neurons,
functional changes in neurons are responsible for that? And how long does that last? Let's say I come
into your clinic, I'm a subject in your
experiment, I take-- come in the morning, I
do my psychedelic journey five or six hours later. I'm parachuting back to
reality, as we call it, and then I go home. Increase connectivity
lasts for how long, and how long are the structural
brain changes occurring? ROBIN CARHART-HARRIS:
Well, you're asking fantastic questions,
and partly because we don't have the answer yet. But we do have some data. And so we have looked
at, first of all, in a sense, the functional
plasticity of what we assume it to be or at
least the functional changes, the increase in
communication across systems that increase in
global connectivity, functional connectivity. Do we see it after the trip? We know we see it during the
trip pretty well replicated correlating with
intense drug effects. Do we see it after the trip? Well the answer
is, we've seen it in two different depression
cohorts, psilocybin therapy for depression. In one study where we looked
the next day, we saw it. A kind of residual effect
similar to what you see acutely being seen the next day. And then in a
subsequent study, we saw it also three weeks later. So we've seen it in two
independent data sets. This decrease in modularity
is how we measure it. It's the same
thing, essentially. Broadly speaking,
it's the same thing. An increase in
global connectivity, functional connectivity. And actually,
unpublished we've seen it in healthy volunteers on
a correlational level. Not on an absolute
change level, but if you look at its relationship
to a mental health outcome, and this is an important thing
to stress with the depression work, we saw a relationship
between the magnitude of that change, the decrease
in modularity or increase in global connectivity,
and the improvement in symptom severity. ANDREW HUBERMAN: So interesting. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: And just
to state it a different way, so what Robin is referring to
is when you say modularity, as neuroscientists, we think of
the different modular networks of the brain. The eye talks to a region
of the thalamus involved in vision, which talks to the
visual cortex, which eventually converges with auditory
information, of course. But there's a separation
or modularity of function. This increased connectivity
is cross-modular in during the trip,
but afterwards as well. And you're saying that that
correlates very strongly with the strength of
the therapeutic outcome for depression. I mean, the logical
extension of that is that extreme modularity
of brain function is depressive in some way. Now, we don't want
to go too far, but what does that
mean that increasing crosstalk between different
modules of the brain is so strongly correlated with
a positive therapeutic outcome? ROBIN CARHART-HARRIS:
We don't other than there's a relationship. I mean, this is the thing. We need to be a little careful
not to run with it too far. I mean, there's some
things that it suggests. I think it suggests a more
flexible mode of brain functioning, if you're not
getting stuck in modules or the modules
aren't excessively cut off from each other. But you see different things
with different presentations if you were to
look at cognition. Sharper cognition is
actually associated with more modularity. So it's a rule that's
a little slippery. And we need to be
careful with it. ANDREW HUBERMAN: Again,
forgive me for interrupting, but I think I have
friends who are-- I would say, are
on the spectrum. Who are very linear
in their thinking and extremely
intelligent in the kind of classic sense of
being able to ratchet through hard problems
to arrive at a solution. And then I have
friends who are-- let's just call them what they are. From the creative communities
outside of science that are very expansive,
they see connections between many different
things, but sometimes, you have to-- not all
of them, but you have to catch their ideas
with a butterfly net. And oftentimes, what
they're saying sometimes it just doesn't make any sense. Now, they also produce
incredible creative works. But to have a
conversation with them is anything but a
linear experience. They are not random
thought generators, but there's a non-linearity or
randomness to their processing that's distinct from
these other folks that I'm describing
on the spectrum. And of course, it's a spectrum. There's a whole
range in between. It sounds to me like there
is some therapeutic value to being able to move along
this continuum from the more linear to the nonlinear. Is that correct? ROBIN CARHART-HARRIS:
Well, I think so. Yeah. It's resonating
what you're saying. It's speaking to my intuition. That you could be very
passy, passing things up, chopping things up like an
analytical scientist like I'm doing a bit. ANDREW HUBERMAN: A splitter
as we say in science. You're either a
lumper or a splitter. Yeah. ROBIN CARHART-HARRIS:
The way I'm being very particular about when
to call something psychedelic. That kind of passy analytical
way of thinking you might associate with
a more modular system. Whereas the system that's
more globally, interconnected, and open, yeah. Might be more flexible
and creative and divergent in the associations
and so on so. Yes. That's speaking to my intuition
to how you're describing it. And I imagine, if you take
severe psychopathology, severe mental illness
like a depression, I've always thought that
there's something intuitive about the term itself. Like a depression in a
landscape, which is a halt. ANDREW HUBERMAN:
Physical depression. ROBIN CARHART-HARRIS:
A physical depression that is easy to fall into. And if you do, it's
hard to get out of. ANDREW HUBERMAN: So almost-- if I understand what
you're saying correctly, almost like getting stuck at
one location on this continuum. Because most people don't
reside at one extreme or the other full time. They can kind of
migrate back and forth between expansive states
and more linear states. ROBIN CARHART-HARRIS:
Like you do with low mood. If you're "healthy"
in inverted commas, you can feel your low
mood, your disappointment. But you can spring back. But someone with-- ANDREW HUBERMAN: And you
know you can spring back. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Right. Whereas the suicidal
depressive person or suicidally depressed person, somehow,
at least in my understanding, there's something about that
extreme depressive states and extreme anxiety states,
something my laboratory is a bit more familiar
with anxiety, which alters the perception of
time such that people feel like that negative state
is going to go on forever or that if it goes away, that
it's going to return at random. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Kind
of a vulnerability to the time domain. ROBIN CARHART-HARRIS: Yeah. Yeah. And it's so tragic, that
cognitive bias in depression that everything's
hopeless and that there is no light at the
end of the tunnel. Yeah. Yes. So if you were to get stuck in
that rut and have that bias, then you're cut off
from other things, other sensory
modalities or modules, cut off from the world,
cut off from other people. Stuck in your inner rut. So yes. I think we're sharing
this intuition that a decrease in
modularity or an opening up of the system, the brain
could relate to an opening up of the mind that is enduring
after the psychedelic dosing session. And yeah. And the third replication
was to see in healthies an improvement in well-being. Because they're healthy, we
don't look at depression. ANDREW HUBERMAN:
So these are people that are healthy
walking into the trial? ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Take
psilocybin twice? ROBIN CARHART-HARRIS:
Well, actually they do. But the first dose is
1 milligram, which they don't feel it's a placebo dose. ANDREW HUBERMAN: Quote
unquote, "micro dose." Yeah. ROBIN CARHART-HARRIS: Yeah. We stick EGG on their heads
to measure their brainwaves during each dose. And 1 milligram,
you see no change. ANDREW HUBERMAN: I think
that, you microdosers. No, I'm just kidding. I mean, nothing against
the micro doses. I've always just been
a little bit skeptical based on my conversations
with the scientists actually doing the
work with psychedelics. It seems like the answer
keeps coming back. 1 or 2, maybe 3 macro doses
in a controlled safe setting. ROBIN CARHART-HARRIS:
Well, that's compelling. The evidence for
that is compelling. And that's what's making all
the difference right now. Microdosing is just
appealing, but again, science isn't about
what we want to believe, it's about what's
actually coming through and what seems to
hold up to testing. ANDREW HUBERMAN: I'd like
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claim a free LMNT sample pack with your purchase. Again, that's drinklmnt--
L-M-N-T.com/huberman. Would you say that's right? That one or two or three
sessions, and how far apart are those
typically spaced in time? ROBIN CARHART-HARRIS: Yeah. Typically, one to three
weeks across the sites is the way people are doing
the psychedelic therapy dosing sessions. Two sessions, you know,
Hopkins, Imperial, NYU. That's been a kind
of default to-- we actually use three
in a current anorexia trial, psilocybin
therapy for anorexia. Two patients left
to see after 19 who've gone through the trial. Very exciting results there. ANDREW HUBERMAN: You're
seeing an alleviation of the obsessive thought
about food and a willingness to consume healthier
amounts of food. ROBIN CARHART-HARRIS: Yeah. Even improved weight
at the long follow-up. ANDREW HUBERMAN: So critical. When we did an episode
on eating disorders, I learned that anorexia
nervosa, which by the way folks, the rates are not increasing. It's been pretty
stable through time despite what's said about
social media, and et cetera. But anorexia nervosa
being the most deadly of all
psychiatric illnesses, which is a big statement,
because manic depression, so-called bipolar depression,
has a 20 to 30 times the typical suicide rate. Basically, many people with
anorexia, I think is how it's-- is what one says, not anorexics. But people with
anorexia often die. Many of them die. ROBIN CARHART-HARRIS: Yeah. So tragic. So often young people as well. And similarly, with suicide
in terms of premature death. So the tragedy with
psychiatry is so strong. It's so rewarding to
be doing that trial and to be seeing good results. I have to check
myself a little bit that I'm reporting on it in
this really promisory way and the trial isn't yet
publicly released and published. So it's still ongoing as well. ANDREW HUBERMAN: But
that was three sessions. ROBIN CARHART-HARRIS:
It is three sessions. And I can't say what the dosage
is, because we still have-- there is a blinding component. But there are three
dosing sessions in there. Let's see now. I think they're two weeks
apart and we do the follow-up. Yes. ANDREW HUBERMAN: I'd
like to close out this description of the
journey and the trip by extending past the
day when people actually take the drug into this--
what I've described as the integration phase. You have to re-integrate. All this increased connectivity
during the session. Hallucinations, insights,
anxiety, letting go. Maybe revelation,
maybe epiphany. OK. Great. At what point is
that consolidated? Meaning, are these
patients or subjects in studies having
daily conversation with their therapist? Are they journaling every day? And I want to keep in mind
that most people are not going to be part of a clinical trial. And of course, here
we're not suggesting what people do or not do. But let's just put it this way. Were people to use psychedelics,
what is the way that people can maximize on the neuroplasticity
and the brain changes in a positive way in the
days and weeks afterwards? In other words, how long does
this so-called integration last? And how far can we take this? I mean, I could imagine
that how often one chooses to think
about the insights could also have an impact. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Right? Because clearly people
went to raves, clearly people did psychedelics
in the '60s. We don't know if clearly
people do psychedelics now. But we don't have
data on those people. You have access to the
understanding of how they're spending their time and
the therapeutic outcomes, which we haven't gotten to
the numbers yet, but again, are incredibly impressive. In upwards of, as
I understand it, 60% or more people getting
relief from depression. ROBIN CARHART-HARRIS: Yeah. 70%, yeah. ANDREW HUBERMAN: 70%. Incredible, especially
when compared to the typical antidepressant
treatments and so on. So what is this
business of integration? How is it done properly? ROBIN CARHART-HARRIS: Yeah. Yeah. Gosh. Well, how long does
it last as well? A lifetime? You know? Life is a journey like
a trip is a journey. And there's always work to do. As Jack Kornfield says, after
the, ecstasy the laundry. And you know? ANDREW HUBERMAN: I love that. ROBIN CARHART-HARRIS: Yeah. Yeah. There'll be other good ones
as well, but forget them. But yeah. So the work is
ongoing, and yeah. But this gives you a foot up. It enables people to do the work
more easily, and that's true. The classic psychedelics
is also true. Very true of MDMA therapy for
post-traumatic stress disorder. It's really giving you a
leg up, making it easier to do very, very difficult
work going back to a trauma. Trying to digest it,
process it, integrate it. So it's such an
essential component of the treatment model. But one has to be realistic
as well by saying, oh, integration lasts a lifetime. Well, people
delivering a service can't be there for a lifetime. So what's the answer there? And people are wrestling
with that issue right now. And I think one of the solutions
might be that it's, in a sense, on you to appoint. The therapeutic team
can treat you to a point and then it becomes what
you might call practice. In a similar way, that
meditation is a practice. It's something that
you have to keep up. And if it slips, then
things could slip. And that's the way it is. Or you have another
psychedelic treatment. So people have even used
this term of practice in relation to
psychedelics, where there's a psychedelic practice
like there's a meditation practice. But I'm using meditation
intentionally here because they actually think that
meditative practice, elements of spiritual practice could
be a very important complement to psychedelic therapy. And I think it's probably
doing something similar in terms of promoting
an ability to sit with-- a former colleague of
mine said it quite well. In relation to
psychedelic therapy versus chronic
pharmacotherapy or like SSRIs being on them all the time. Says psychedelic
therapy allows you to sit with rather than sit on. And so that's quite good. Yeah. So the meditation, the
mindfulness, the ability to, yes, be present-centered
but also present-centered and accepting so
if things come up, you can watch and
process and then let go. ANDREW HUBERMAN: That
Holy Grail of mindfulness. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Awareness
without reactivity, respond. I grew up in the
Bay Area and you'd hear this language, right? And I'm not being
disparaging this. I have friends that are on
the board of Esalen and work down there. And I've gone there. And yet you hear
these terms, right? Be responsive, not reactive,
which to a neuroscientist is like grates on me,
which probably just means I have issues. And surely, I do. But what does that mean? It's saying like, oh,
to be the observer but not be drawn
into the experience. And again, I don't want
to be overly reductionist, but what I find so compelling
about the emerging data, because it really is data,
on psychedelics as treatments for depression and trauma,
namely psilocybin and MDMA is that it really seems to
allow people this space that is so commonly thrown around. Giving space between
stimulus and reaction. Viktor Frankl talked about this. But I've been reading
a wonderful book called The Prince of Medicine. Dates back to the
origins of medicine. Very dense book. People have been
talking about this stuff and thinking about this
stuff for thousands of years. Psychedelics seem to give people
access to that better version of self, which is remarkable. What's also remarkable, it's,
perhaps, worth pointing out is that, five years
ago, I never would have been comfortable
having this conversation. I would have been
afraid to lose my job. Stanford Magazine, this week,
just published an entire issue about psychedelics with
how ketamine works, MDMA, psilocybin with the appropriate
cautionary notes in there. But clearly, times are changing. Speaking of which, I know you're
doing a trial on first-time use of psychedelics. What inspired that? And what are you observing? And as you tell us
that, please give us a few of the key contours. What's the dose, how
old are these subjects? I'm assuming it's men, women. Are they suffering
from depression or not? What's the landscape
of that study? And I realize this is still
early days of the study or maybe it's close
to completion. It's not yet published,
however, correct? ROBIN CARHART-HARRIS: It's not
published, it's not submitted, it is completed. So this was another one of
our COVID studies, in a sense, meaning COVID hit and we
had to finish the study. And it was hard to finish
the study because of COVID. That was true of our psilocybin
therapy versus escitalopram. Lexapro trial, which is
published in The New England Journal of Medicine. But the-- ANDREW HUBERMAN: This was '20--
that paper, by the way, folks, we'll provide a link to
in the show note captions as well as some of
Robin's other papers. I think the 2022 New England
Journal paper is really fabulous given the different
dosages and the comparison to, essentially,
what is microdosing and the comparison
to citalopram. ROBIN CARHART-HARRIS: Mhm. Yeah. That's interesting
that you link the way we gave small doses of
psilocybin to microdosing. We didn't think of it that way. We thought it was just
a necessary placebo for the big dose,
the 25 milligrams. Yeah. So that we could say to everyone
we're giving you psilocybin and not be lying. Yeah. For those who got escitalopram,
Lexapro for six weeks, they got a very, very
low dose of psilocybin. But it allowed us to standardize
all the psychotherapy and so on. But the other study
that you're referring to was in healthy volunteers. Middle-aged. Average age, I think, was 40. So not your typical
student study that is so often the case
in psychology research. All the undergrads end up
volunteering for your study. So this is more of an
age range and also-- I think it was an equal
proportion of male and female. All the staff
actually were female, which the staff were
very proud of them. ANDREW HUBERMAN: Although,
it produces its own potential confound, right? To become all one sex of staff. ROBIN CARHART-HARRIS: Possibly. ANDREW HUBERMAN: Yeah. ROBIN CARHART-HARRIS: They
did a good job in the sense that we saw significant
improvements in well-being at the end of the trial. So let me describe the design. It was a repeated measures
design, meaning people come in, you collect your baseline
data and do a brain scan, and you give people a placebo. We gave people a placebo. And actually let me
rewind a little bit. Everyone's healthy volunteers,
middle-aged never taken a psychedelic in their life. None of them. Entirely fresh, virgin
people coming in. And the plan is to give them
their first ever psychedelic experience. So that's what we
did in this study. But to do it, we have this
repeated measures design where they'll first get a placebo. And we have the
placebo so that we can do all the procedures,
all the therapy, all the music listening but not give a
whopping dose of psilocybin. Again, we gave them a
placebo dose of psilocybin. 1 milligram. We stick EEG headsets
on during the experience to record the brain activity
from the scalp, the oscillating electrical activity. And we do the MRI scanning
before and after to see deeper into the brain, and we can look
at the functional connectivity that we were referring to
earlier, and also properties of brain anatomy, which
we did in this study. So the short story is that
all of the changes that we saw both psychologically
and neurobiologically were seen with
the 25 milligrams. It all happened with
that big whopping dose. And what did we see? Well, we did see
significant improvements in psychological well-being. We saw what I call the entropic
brain effect, which is actually formerly quite accurate. We see an increase in the
informational complexity of ongoing brain activity
recorded with the EEG on the dose of psilocybin. The activity becomes
more complex. It's harder to
predict across time. It's more informationally rich. And that effect
correlates as it does very reliably with the magnitude
of the subjective effect. So the bigger the trip, the
bigger this entropic brain effect. Now, pretty well
replicated finding. But then the MRI, seeing
deep into the brain was probably our
most exciting result where we didn't just see some
functional brain changes, but we've seen some anatomical
brain changes as well. And we used a technique called
diffusion tensor imaging that looks at the cabling of the
brain, the white matter tracts. And we saw a change
in major tracts. So we limited our search
space to really thick tracts. Really thick fibers. And the fibers that
came through as changing were ones that traveled
between the prefrontal cortex and the thalamus
and the striatum. There were two tracks, two
prefrontal tracks that changed. And they changed in the
direction of a decrease in axial diffusivity,
which could be interpreted as tract integrity where
a decrease would be an increase in tract integrity. It is something that you
see in the developing brain. The axial diffusivity
decreases as the brain goes from being a baby
to being an adult. Axial diffusivity goes down. And then in aging and
pathologies of aging, axial diffusivity goes up. ANDREW HUBERMAN: This is
in the opposite direction of the results you talked
about earlier in terms of brain connectivity
of increased communication across areas. If I understand
correctly, and I'm perfectly happy to be wrong,
by the way, that this decrease in axial diffusivity
translates to a higher fidelity of communication
between the prefrontal cortex and the thalamus and
striatum as opposed to less. And your description
of this as somewhat like the transition from
babyhood and childhood to adulthood. Speaks to the same where
we know that there's a massive culling of
connections as opposed to growth of connections. So in other words,
as we get older, we get better at
doing certain things and less good at doing
potentially most everything else. Is that right? ROBIN CARHART-HARRIS: Ish. Because the change was
anatomical and not functional. So the other stuff was is
really measuring communication in the brain by looking at
how the activity fluctuates across time and whether those
fluctuations in activity are synchronous between regions. And if they are, we say
they're functionally connected. And we infer that they're
talking to each other, because they go up
and down in synchrony. But when it comes
to the anatomy, we're talking about the
just static material stuff. And so we're seeing the fibers
and a property of the fibers change. At least that's what we think. And recently, we had
an independent person come in and reanalyze the data,
because one of those things, incredible finding
requires credible evidence, really strong evidence. And I would say, the evidence
at the moment is one study. So we need to be
cautious on that. But we did re-analyze it
and use this correction procedure-free water correction
to be more sure that it was a change in the
actual microstructure rather than something to do
with the extracellular space. The water surrounding
the fibers. And it came through. In fact, the change
was strengthened by doing this correction step. ANDREW HUBERMAN: So
this is neuroplasticity as the consequence of one
first time session with 25 milligrams of psilocybin. ROBIN CARHART-HARRIS: Yeah. Yeah. So we're excited and the two-- ANDREW HUBERMAN:
Understandably so. ROBIN CARHART-HARRIS: --the two
different-- the second analyst coming in wasn't
sure she believed it and then she thought this
correction technique might kill the result and then it came
through, and she's like, OK. Now, I'm excited too. So we'll see. We don't know what it means. What does it mean functionally? We don't know. How did the people change? Well, psychologically, as I
said, well-being improved. We did look at their
cognition, and we used a cognitive
flexibility paradigm that looks at people's ability
to notice a rule change and then flexibly adapt their
behavior based on noticing this rule change and people
improved after the 25 milligrams and didn't
significantly improve after the placebo dose. There weren't correlations with
the DTI change, the cabling change and these
psychological outcomes. But with these studies
and smaller sample sizes, you don't always see those
correlations come through. So it's something. We don't know what it means. But it's a change
in brain anatomy that's in the opposite
direction to what you see in an aging brain
or with pathology of aging. And it's what you see
in a healthy brain as it goes from normal
neurodevelopment into adulthood. ANDREW HUBERMAN: Very, very
exciting and intriguing. And I appreciate
that you highlighted that it's just one study,
although from everything you've said, it sounds like it's
been done with immense rigor. So we will eagerly await the
publication of that study so we can peruse all the data
and the subsequent studies. I want to hear a
bit about the study that you have been carrying
out on the use of psilocybin for the treatment
of fibromyalgia. I'm intrigued by
fibromyalgia, because I have a good friend who also-- I won't reveal who it is. No. It's not me. This isn't the "I
have a friend thing." Who also is a scientist who
sits at a fairly high position in the National Institutes
of Health who quietly has expressed to me
that they are incredibly frustrated with the fact that
the standard medical community has largely ignored
fibromyalgia. And that for many years, it was
lumped with things like chronic fatigue syndrome and
other so-called-- again, so-called. I'm not saying this. But people often
refer to these as, oh. It's psychosomatic. That's all in your head. Which, as a neuroscientist, is
a ridiculous statement to hear, because it's all in your head. Your brain is in
your head after all. Your physiology
and your psychology are influencing each other. Of course. And the world is starting
to appreciate that more. But first of all,
maybe you could tell people what
fibromyalgia is, what inspired you to do
a study on fibromyalgia using psilocybin of all
things because that's surprising to me. And if you are allowed
to or if you have access to the data in
mind, share with us a little bit about what you're
discovering in that study. ROBIN CARHART-HARRIS: Sure. Yeah. Happy to. So again, it's psilocybin
therapy and the population is fibromyalgia syndrome. So this is people
presenting with a generalized chronic pain. So unlike some
other pain disorders where the pain is focused. You can say, it's my lower
back, which is very common. Chronic lower back pain. This is more generalized. And for that reason, it's
hard to know what it is. And that's why it's been a
controversial space in medicine and it's been-- yeah. It's had that charge thrown
at it that maybe it's psychosomatic, and
just to your point, is anything ever independent
of the mind, anyway. But this is actually
a fascinating space for how subjective experience,
the lived experience, and the mind can
influence the body. Because there's some really
interesting literature around the etiology. How the pain has come about. In a sense like what
caused the pain. What's the story there? And the head of the trial, I
would say to my colleagues, let's just be careful. Because there is some
fascinating literature around things like a
background of trauma and how that can relate to
issues related to inflammation and how that can
express into things like fibromyalgia syndrome. I just said, be
very careful there, because if you go in
with an assumption that there's some buried
trauma, for example, then there's that
whole other side of psychoanalysis that
massively tripped it up around false memory and so on. And so please don't
hold prior assumptions that you're going to uncover
buried trauma in every case. Now, the team of
treated, I think, eight people and it
is going very well. Again, I just want to
be careful with how I describe it to manage
expectations and not get too carried away. But I check in with
the team every week, and they're still based
in London doing the work. And it's remarkable what I hear
about the profound experiences that people have under the drug. In this study, we
only give one dose. It's a very mechanistic study. We actually have the EEG
cap on in the sessions like in the healthy
volunteer study, but this time now taking it
into a clinical population. And-- ANDREW HUBERMAN: So they
are wearing an eye mask under the influence of 25
milligrams of psilocybin. Most of them probably have
not done psilocybin before. So it's a little bit like the
first time study in some sense. They have fibromyalgia that's
debilitating in some way. They don't want it, obviously. And during the session, are
they thinking about their pain? Are they being told to
think about their pain? ROBIN CARHART-HARRIS:
They're not being told to think
about the pain. In fact, as I understand it,
while there is a therapeutic model around acceptance
of the pain, it isn't-- unlike some of
the PTSD work, you aren't encouraging them to
focus on the index trauma and then work through it
and try and digest it. We don't do that with the pain. So the pain is there, but
there isn't an invitation to focus on it. And that's probably
one of the differences with classic psychedelic
therapy versus MDMA therapy. Arguably, MDMA therapy is
more like it's a bit closer to traditional talk therapy
where there is more dialogue. People are able to talk on MDMA. ANDREW HUBERMAN: In
the MDMA trials, do you know whether or not
they used eye masks or-- because this seems to be
an important distinction between, as you described,
the therapeutic trip versus the trip that one
does going into the woods and taking psilocybin in
the woods or at a party or while staring at
a poster or a leaf. Again, I'm not trying to
trivialize those experiences. I mean, obviously,
they can be profound. So I'm told. But the MDMA trials
seem to involve, as you said, more
directed dialogue. And sometimes, even
empathic connection between people by
they're actually looking at one another,
the eyes and eye contact being such a key part of
the human social cognitive connective networks. So do you know if they
put eye masks on people during the therapeutic session? ROBIN CARHART-HARRIS:
I'm pretty sure that they have the eye masks there. ANDREW HUBERMAN: Right. Because a lot of
the MDMA work, and I was part of an MDMA trial. Was, as I understand
geared toward developing, because it's an empathogen
empathy toward the self. ROBIN CARHART-HARRIS: Yeah. I'm pretty sure they
have the eye masks there, but they probably-- and
it's a great question, because you could
formally test this. It probably don't
use them as much. ANDREW HUBERMAN: Mhm. ROBIN CARHART-HARRIS: The
thing is with the classic psychedelics, if you're
looking at your guides or your facilitators and
their faces are melting or-- ANDREW HUBERMAN:
On MDMA, you just might really start to feel
more connected to you. ROBIN CARHART-HARRIS: Yeah. They might look especially
beautiful and you know-- ANDREW HUBERMAN: sure. Yeah. ROBIN CARHART-HARRIS: And yeah. There's that fascinating
effect of loving the people that you're with. And so yeah. I imagine they talk more
and use the eye shades less. And it is more interpersonal
rather than like intrapersonal or going inside. They do use a
fascinating terminology that some people have critiqued,
but it is a very interesting phenomenon. And it's this notion
of the inner healer. They use that language a lot. It's been critiqued because
it sounds very suggestive. You know? And that's probably one
of the vehicles here. Driving the therapeutic
process is suggestion. I think we have to
be honest about that. So when they go inside,
that's another term that we use very much in the
classic psychedelic therapy work. You go inside. You put the eyeshades
on, and people are encouraged to go inside. But when they do that
in the MDMA work, especially, they might
be told explicitly and listen to the inner
healer and that language. So you could see how
a cynic or a skeptic could come in and see that as
some kind of like suggestive priming or biasing. I think they have a point. Skeptics often do, but I don't
think it's all of the story. And just briefly, because
it's an interesting point, speaking to that point
a bit in our psilocybin therapy versus
escitalopram trial, we measured
pre-trial expectancy. And we did it for
both conditions. So what kind of
improvement do you expect with the Lexapro,
the escitalopram at the end of the trial? And what kind of improvement if
you go into the psilocybin arm and get two big
doses of psilocybin. What kind of improvement do you
think you'll see in that arm? And of course, it
was a coin flip as to what arm people went into
and there was no crossover. What we found was that it was
true that we had a sample bias, so most people had higher
expectation stations. On average, there were higher
expectations for psilocybin and its efficacy
or effectiveness versus the SSRI, the Lexapro. However, when we looked
at the correlation or the predictive relationship
between pre-trial expectancy and response, we saw
that pre-trial expectancy for the escitalopram
predicted response to escitalopram across virtually
every single measure, all these different measures
of depression and anxiety and well-being, and I
think none of the scales. I'm pretty sure it was none of
about 12 or so mental health rating scales. Was there a relationship
between pre-trial expectancy? Even though it was high,
it didn't predict-- pre-trial expectancy
didn't predict response to the psilocybin therapy. So that was a bit of a smash
on the head for the idea that the classic
psychedelic therapy is some kind of placebo response. And I think it's so important
to address that question. Because if it
doesn't come through as it didn't come
through, then it opens up even more intrigue
about, well, what is it then? If it's not just a placebo
response or a super placebo response like an amplification
of the placebo response, then it must be something else. And how intriguing? It has a direct
therapeutic action. It must be something. And we don't yet
know what it is. I talked about the
residual increase in global connectivity. That's one possibility. But the truth is, we're
just scratching the surface. ANDREW HUBERMAN: And yet
the therapeutic outcomes are, again, just so
marvelously impressive. I'm curious as to why as-- well, there are that many labs. But the laboratories that are
focused on classic psychedelics for the treatment of
depression and now as you mentioned, promising results
for anorexia and fibromyalgia as well. Although preliminary
very promising. Why the lack of
attention toward LSD? Is it that the LSD
trips are just too long? Is it that they are
qualitatively different? Are there any data on
non-microdoses of LSD? And here I want to
be very careful, because I learned through my
interactions on social media that this term microdose
is very misleading. And in some cases, can be
dangerously misleading, because, as you
mentioned earlier, the effective
psychedelic dose or the-- effective meaning
that can induce a real trip with hallucinations,
et cetera, of LSD is actually in the
microgram range. So some people hear microdose,
and they think microgram of LSD is a-- micrograms is a
microdose when, in fact, a macrodose of LSD can be
measured in micrograms, right? So this is where in the
absence of scientific training, people can really go astray. Or even just in lack
of understanding of the metric system. And since now you're a
recent arrival to the US, fortunate for us. Sorry. England's loss is
the US's gain by-- Robbins Lab moved from England
to the United States recently. So score 1 for us. But why isn't there more
use of LSD in these trials? ROBIN CARHART-HARRIS:
I think it probably is the duration of the trip. It used to be stigma
and it was easier to get your psilocybin
study through, because others were, they
were getting that through. So there was the likes of
Franz Vollenweider in Zurich in Switzerland and
then Roland Griffiths coming along and doing the
psilocybin work at Hopkins. So you could appeal
to that precedence and say, well, they're
doing it over there. Can we not do it
in little England? So that's how it worked for us. We did actually go on
and do an LSD study once we'd laid the foundations
for doing this kind of work. And it was a brain
imaging study. It was a really
extensive one actually where we used both MRI
and another modality called MEG, sort of
super EEG in a sense. But you know, why didn't
that turn our heads to think, oh, should we not
be doing our trials with LSD? It does have something
to do with the pragmatics like a study day with
psilocybin is long enough. ANDREW HUBERMAN: So
four to six-hour trip? ROBIN CARHART-HARRIS: Yeah. And the FDA asked us to
have the people in the lab until eight hours post-dose,
which personally I think could be quite excessive,
especially if it's a low dose. And if you have that in the
placebo condition as well, it becomes impractical. ANDREW HUBERMAN: Yeah. Scientists are not
paid nearly enough to warrant the-- there's
no such thing as overtime for the graduate
students and postdocs. ROBIN CARHART-HARRIS: Yeah. It's often those
more junior members that are doing that
really hard work. ANDREW HUBERMAN: It was
described very well to me by a student when I was-- a
graduate student said to me, they really can't afford
to pay us by the hour. Because we used to work. He was a electrophysiologist,
so he would run experiments. No joke, folks. Three to five-day experiments. Sleeping in bouts of
two hours here or there in a dark room with a bunch
of equipment and recordings. So these are long, long
acute electrophysiological recordings. So yeah. No scientist does it for
the money, I promise you. There is money in
pharma, there is not money in personal income. It's not lucrative for
the basic scientist. So yes. LSD is what? Anywhere from 8 to 15
hours, something like that. ROBIN CARHART-HARRIS: Yeah. 15 would be a little long. You'd be a bit worried
if you were still tripping at that time, maybe
with a really big dose. ANDREW HUBERMAN: Oops. No. Just kidding. ROBIN CARHART-HARRIS: Yeah. Eight hours plus-- and
dose dependent, yeah. If it's a bigger dose,
it's a longer experience. But if you're going
to dose say, 10:00 AM in the morning, which is more
or less how it often goes, then that's 6:00 PM still
feeling the effects. And then how long do you
wait now to close things out before they can go home. Even with psilocybin, you
have people still at work into the evening. And the staff are
always there later, of course, because they've
got to pack up and yeah. So these are long days. And it's too much, you know? ANDREW HUBERMAN:
That makes sense. Practical constraints. I learned from a recent
guest on this podcast that we recorded with,
Dr. Satchin Panda who is a colleague of mine when I
was down at the Salk Institute. Pioneered a lot
of the studies on so-called intermittent fasting. That the reason that the eating
period in these studies-- in animals and now
on humans is 8 hours, the feeding window
in these studies is because the graduate student
was going to, otherwise, lose their relationship. Because their significant
other says, listen, you can be in the lab
for 12 hours, that meant some hours before the
experiment, then 8 hours, and then some hours afterwards. But you can't stay
in there longer. And many people use the
eight-hour feeding window as a consequence. So the scientist has to
exist and be carried out in real-world frame. ROBIN CARHART-HARRIS: It does. ANDREW HUBERMAN: Yeah. ROBIN CARHART-HARRIS: It does. ANDREW HUBERMAN: MDMA is a
little bit shorter, right? It's about a four to-- it's also about four
to six hours, correct? ROBIN CARHART-HARRIS: Yeah. It's kind of similar
to psilocybin. Yeah. It is. And actually, in
the maps work, they redose after a certain point. ANDREW HUBERMAN: The booster. ROBIN CARHART-HARRIS: They have
a booster or optional booster, yeah. So there is that. And now, people
are thinking, well, even the psilocybin sessions
are long and expensive. And if you have to have
two staff members there all the time, that's expensive. That's where most
of the expense is. Is in the staffing. So can we abridge the
experience, make it shorter, and get away with it, and get
similar therapeutic outcomes? So there's a lot of
interest in that direction. ANDREW HUBERMAN:
May I ask about-- sorry to interrupt,
but I want to make sure I don't forget to ask about
combination psilocybin MDMA therapies. The reason I ask about this is-- and here, truly
not me, but I know people who do
self-administered combination psilocybin and MDMA. I think I heard this right. I think it's called
a hippy flip. There's another one
that involves LSD too. Again, I'm not suggesting people
do these drug combinations. But the way it was
described to me was that the psilocybin,
because it's so serotonergic, sometimes can be not a downer
but can have a bit of kind of a murky feel to it. Some real deep
introspection, sometimes in the darker realms of one's
psyche depressive thoughts, et cetera. Not that it necessarily stays
that way throughout the trip, but that the MDMA,
because it has a very strongly serotonergic
but also dopaminergic-- I mean, it has an
amphetamine component. Cocaine-like, in fact. If you've ever seen
someone on MDMA, their pupils are about
the size of a quarters. For a reason, they're
extreme autonomic arousal compared to a sedative,
which by the way, would constrict the pupils. So they describe the use
of MDMA to balance out the affect component of it. What are your thoughts on
combination psilocybin MDMA? Does this hold any
therapeutic potential? This is, obviously, backyard
chemistry in the sense that people are cowboying
this stuff on their own, which again, I don't
really recommend. I'd like to see the
science go first, but I understand this is how
it works in the real world. Yeah. What are your thoughts
on combining compounds? ROBIN CARHART-HARRIS: Yeah. Well, I guess, they're cowboying
it in recreational context, but also underground therapists
do work with this combo. ANDREW HUBERMAN: That's
what I'm referring to. So I'm not talking about people
partying with this stuff. I'm talking about there are
thousands now of therapists that offer psychedelic
therapies illegally, really, because it's not
legal at least, not in the US, to possess or sell. But that are doing this. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: So that's
really why I'm asking. ROBIN CARHART-HARRIS: Yeah. And I think there's
something to be said for-- one has to be careful
with this as a scientist. But if they're doing
it, are they using some kind of trial and error? The same is true, of
course, with longer history of psychedelic plant
medicine use if by plants, we include the fungi as well. So in the extended sense plants. There will have been
trial and error there. It might not be as systematic
as the science we do today, but maybe there's been
a learning process. And maybe what they
do, they've come to because they found it works. So by that principle, I'm
interested in that combination and whether it does offer
some advantages, maybe, in certain patients. One of the buzz
terms in medicine these days is
precision medicine. A precision medicine and
personalized medicine. So maybe there are
certain cases where introducing say, psilocybin
after the MDMA or the other way around could offer
some advantages. And the differences
are interesting. Psilocybin can get
you to deep places. Maybe the kernel of your
suffering and major life experiences and complexes
that are causally linked to whatever the pathology
that you're presenting with. But it can do it, sometimes,
quite aggressively. And if it say, post-traumatic
stress disorder, it can be overwhelming. And you can fight it. And really, it's that. The resistance is
really challenged, and they fight back. And the therapeutic
breakthrough and the progress isn't happening because
you've agitated the defense mechanisms. Whereas what MDMA offers
is something arguably more directionally reliable
in terms of the valence. It's more directionally positive
generally, an MDMA experience. ANDREW HUBERMAN: Hard to
have a bad time on MDMA. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: To be
quite blunt, I mean. But one of the concerns
I had with MDMA, I've never done
it recreationally. I have had not and have not
ever done it recreationally. But when it was done in
this therapeutic setting, I realized, because there was
a music on at the beginning, I actually asked
them to turn it off, because I realized that
the music was becoming such an attractor
to my attention that I suddenly was starting
to think about music and my love of
music, which was not the focus of the session
that was there for. And I'm glad that they
did turn the music off, because the moment
they did, I was able to drop in within the eye
mask to this sort of go inward and address some certain
issues that at least to me felt key and productive. So that seems to be the
kind of hazard with MDMA. Is that it's such an empathogen
that one could start to-- you could go down any number
of different rabbit holes. ROBIN CARHART-HARRIS: Yeah. But it's also-- it's a
strength, because you well, the classics like psilocybin
can take you there very reliably but maybe a bit aggressively. MDMA makes it
easier to go there. And that's its strength. And that's why that marriage
of MDMA therapy for PTSD, in particular, is a good combo. It works, because you
are going to go there. In a sense, you have to really
make the therapeutic progress. You're going to have
to go back there. But we're going to set it up
so that you can go back there and feel safer and
more trusting and be able to go back there whereas
you've never, otherwise, been able to go back there
without dissociating or having horrible flashbacks and so on. So that's the strength
that it offers. I guess the limitation
would be that, maybe, it doesn't take you as deep as
the classic psychedelics. And I tend to think
I'm biased on this one, that there's a kind of
honesty to the classics in that it is hell
as well as heaven. And that's the psyche. It isn't all roses. ANDREW HUBERMAN: I
really appreciate that you bring that up. Because I think that
there's such a fear of so-called bad trips. There's such a fear in
non-psychedelic states to avoid the painful and
everything we know from trauma and the treatment of trauma. And we've had several
guests on here. And my close colleague, close,
close colleague at Stanford, Dr. David Spiegel, our
Associate Chair of Psychiatries, Clinical Hypnotist. Amazing human being and
scientist and clinician, has really just embedded
this in my mind. That the only way
to deal with trauma is to get right up next to
that trauma to the point where some relief
is experienced. There is no other real way. And so, I really
appreciate that you're saying that the classic
psychedelics may offer with a very strong
nudge, perhaps, the opportunity to get into
the uncomfortable in a way that MDMA or some non-classical
psychedelics, perhaps, do not. We were talking about time
frames or duration of trips and these different
compounds and how they differ and how they're similar. I'd love for you to educate
me on DMT and some of the work that you're doing with DMT. My understanding is that it's
a very brief trip minutes. People I know who
have done this. Again, therapeutically,
actually, I'll just point to one very
exciting, I think, group and initiative which
is the Veterans Solutions Initiative, which is a group-- this is carried out in
Mexico, but in conjunction with laboratories at Stanford
and elsewhere who are evaluating the neural changes. And this involves
ibogaine, which is iboga, which is a very
long duration psychedelic. 22 hours or more, followed by I
think one or two doses of DMT. This is for veterans to deal
with any number of issues. Appears to be working
with great success. And I've spoken
to several people who've gone through this. And the way that they described
DMT, almost across the board, was quote, here I'm just
pulling quotes, right? Anecdata. The most profound experience
of my entire life, even greater than the
birth of my children, quote, "like being attached to
the shockwave of an atom bomb." Quote. "There's no way I
would do another dose, because the first one
was so unbelievable." Interesting, by the way. I think most of
us, including me, would think, why wouldn't
you want to do it again then? But this idea that that
was just beyond anything. So these are
significant-- excuse me these are significant
statements coming from individuals
who have existed at the extremes of human
experience to begin with. These are so-called
tier 1 operators within special operations
who exit and may or may not have trauma. But DMT sounds like a big deal. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Short
duration, really big deal. What do we know
about its chemistry? What do we know about how
it's impacting brain networks? And what in the
world is going on that people are
describing it as the ways I just mentioned
a few moments ago? ROBIN CARHART-HARRIS: Yeah. It's a rocket ship. If the psilocybin is like a
ship leaving port, then yeah. This is a rocket
ship into craziness. ANDREW HUBERMAN:
Is it serotonin 2A? ROBIN CARHART-HARRIS: It is. Yeah. So it is a classic psychedelic. It's a direct agonist, a direct
stimulator of the serotonin 2A receptor. It's an order of magnitude
less potent than psilocybin. But potency is a funny thing,
because it's dose-dependent. So that doesn't mean that
the experience with DMT is less than that of psilocybin. It's just that you
give more of the drug. But that's matched
by it's stickiness for the serotonin
2A receptor, which is this kind of golden rule
in psychedelic sciences that it was discovered
in the mid 1980s. This tight relationship between
the affinity or the stickiness or the binding potential of a
psychedelic for 2A receptor, in particular. Serotonin 2A and its potency. And the stickier the
drug, the more potent. So LSD really sticky. Very, very potent. You only need those
tiny microgram doses. So DMT, by its affinity,
is a little less potent, but by its effects when
you give a standard dose, it's just wild. And DMT, because there's another
compound called 5-methoxy DMT, which is a bit different
pharmacologically and subjectively, it's similar
in terms of its kinetics. It's another rocket ship. Both compounds in the wild,
so to speak, are smoked often. DMT and 5-MeO. People are vaping
both actually now. There are vape pens that are
being developed for people to administer this,
but more traditionally, it's been a smoking thing. ANDREW HUBERMAN: This is
clinically not recreationally or both. ROBIN CARHART-HARRIS: Both no. I mean, underground
practitioners are using the vape pens. They like them because
people titrate the dosage. They get a feel for what it
is to be going into this state so that they feel they
can let go and go into it. And actually, I think
some of the veterans work might be giving 5-MeO
after the ibogaine. Phenomenologically, if there's
a difference between DMT and 5-MeO, people
might put it on 5-MeO being more of a reliable
ego dissolution experience. Less visual and more
all round immersion in the greater whole
loss of self-identity and just immersion
in everything. ANDREW HUBERMAN: Yeah. Maybe we could just talk about
ego dissolution for a second, because it's such a
sticky, interesting idea. I can take a step back as a
neuroscientist and say, OK. Ego dissolution. This idea that-- from
a very early age, we have a concept of self and
that I wake up every morning and I know I'm me and
not somebody else. And presumably, you do the same. And most people do the
same, I would hope. And that there are
objects in the world and people in the
world beyond us. But every time I hear
about ego dissolution, it sounds like it's kind
of a temporary elimination of the idea that
things start and stop between us and everything else. Almost like in a kind
of a-- here I'm not trying to sound philosophical
or metaphysical, but there's the molecular
continuity of life, right? We're all just little bits-- ROBIN CARHART-HARRIS:
Which is true. ANDREW HUBERMAN:
--which is true, right? Not a functional way to
go through the day, right? Because you want to
make a cup of coffee, you don't really want
to get lost in that if your goal is to
make a cup of coffee. But what is the power
of ego dissolution? Is it the idea that we belong,
is it a sense of meaning? Is it the sense that we're
not as important as we think, which, of course, could be
a wonderfully useful way to go through life? To think that we're not as-- like we are vitally important,
but we're not the only thing, right? Because I do believe connection
is vital as most people do. What is ego dissolution? And why would this serotonin
2A activation cause that? That's remarkable. ROBIN CARHART-HARRIS: Yeah. Great questions. I mean, what is it? You alluded to it with
the start/stop, I think. Because you could
define it by boundaries. In a sense what isn't
me is as valid here as the a developing
sense of what is me that a child
develops at whatever age. And so a major characteristic
of the ego dissolution experience rather than just a
negative, a thing going away. My sense of self going
away is the positive. Oh. Now, I feel interconnected
with other people and the world at large. And I realize that there is
that molecular continuity. And actually, that's
a ground truth. And oh, maybe the ego thing is
somewhat illusory or at least a construction of my mind. ANDREW HUBERMAN: And
indeed it is, right? ROBIN CARHART-HARRIS:
Well, it is. Yeah. I mean, there's no
transcendentalism about that. It's just not like logic. ANDREW HUBERMAN: I think we
are about it a little bit like family. I mean, we all know what
immediate family is, but it's like-- forgive me for
interrupting myself. I do it all the time, anyway. When I teach neuroanatomy,
some clever student always figures out, OK. Well, that's connected to
that and that's connected. But ultimately,
everything in the brain is connected to everything else. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: There's
just no way around that. That's a true statement. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: And
so you really just have to decide where you
draw the boundaries between-- ROBIN CARHART-HARRIS: Yeah. Where do you draw the line? ANDREW HUBERMAN:
Where are the modules? What are the modules? You could say, the brain is
just one big macro module. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: And then you
also want to include the body. And now fortunately,
people are starting to embrace this idea that
it's not mind-body, it's both. Because the nervous
system extends through both, of course. So the same could
be said of family. We're related, right? Not just by virtue of the
fact that we're human beings. If we did our
genealogical charts, we would find a
convergence at some point. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: And of course,
this becomes a bit of a game. But then one realizes that
where you draw the boundaries and if you draw them at
brother, sister, parents, biological parents, et
cetera, that's a game too. And so it is just a construct. ROBIN CARHART-HARRIS: Yeah. I mean, it is a fun game. Where do you draw the
line and when to pass and when to collapse. It's also a classic
consideration in science when to pass and when-- ANDREW HUBERMAN: That
lumper versus the splitter. ROBIN CARHART-HARRIS:
There you go. It's brilliant. Yeah. But you asked this
question, like, well, why does psychedelics do it? And there, we think
psychedelics do it, because the target
receptors, at least, classic psychedelics do it. And that's important to stress. So MDMA doesn't really
do it in the same way, might soften the ego a bit. But yeah. That's debatable. ANDREW HUBERMAN: My
experience with MDMA is that it's such a
strong empathogen. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: And that it
can cause empathy for others. Certainly, you could
imagine situations where one in MDMA
journey and afterwards says, oh, my oppressors are
the people that harmed me. And here I'm not referring
to my experience. But they did the best
with what they have. Actually have empathy for them. Forgiveness. But also for oneself. That there's an
empathy for self, I know I said this earlier, that
is very hard for most people to access. Perhaps, not the narcissists
out there listening. They'll be like, of
course, empathy for self. But everyone else, I think,
all the other healthy people or the healthy people
other than narcissists and not picking on narcissists. I have to imagine
they suffer too. In fact, I think that's the
root of their narcissism. That empathy for
self is not something that comes reflexively
for most people. And here I'm not talking about
self love or self respect. But this notion of being able
to see the self as not just deserving of love and
care but actually holding that in place while
in confrontation with something challenging
in a way that allows a more, not less access to adaptive
responses to that challenge. I think that's the way
I conceptualize it. ROBIN CARHART-HARRIS: Yeah. Yeah. I mean, drugs offer a great-- they offer great-- they
are great scientific tools for tackling this question. What is ego dissolution, and
why do drugs modulate it? And what does that tell
you about the brain? Because other drugs
like cocaine releasing more of a different
neurotransmitter, dopamine more than serotonin. The opposite is
the case with MDMA. Is more of an ego
inflator, right? ANDREW HUBERMAN: Oh, absolutely. People will become
hyper-linear, hyper-linked to their own desires and wishes,
and future outcomes become an obsession. It's the stuff of
American Psycho and the cliches and stereotypes
of the '80s cocaine culture. ROBIN CARHART-HARRIS: Yeah. Yeah. We did a study once
actually looking at dose-dependent relationship
with ego inflation on one axis and ego
dissolution on the other and saw that it just massively
passed or differentiated between cocaine
and psychedelics. It's quite a neat study. ANDREW HUBERMAN:
So cocaine makes people's egos super inflated? ROBIN CARHART-HARRIS: Yeah. And doesn't touch
dissolution and the opposite is the case with psychedelics. ANDREW HUBERMAN: Is
there any neuroimaging to explain how
cocaine does that? ROBIN CARHART-HARRIS: That
would be a great study. Yeah. Great idea. ANDREW HUBERMAN:
We should do that. I have a sabbatical coming up. I've got 12 months of
sabbatical coming up. ROBIN CARHART-HARRIS: Yeah. That's-- ANDREW HUBERMAN: I'm going
to show up in your lab. ROBIN CARHART-HARRIS: Yeah. That's a really good one. If it's all right to finish
the thread on why psychedelics and ego dissolution,
we do know some things or we have some hypotheses. And it's that the target
receptors, the serotonin 2A receptors that classic
psychedelics hit, are heavily expressed
in what these days I like to call recent brain. Because evolutionarily,
it's recent brain. It's cortex that humans have
more than any other species. If you look at a mapping of
cortical expansion from say, macaque or chimp to human,
it's the very same map that you'll find
the 2A receptors in. So that's the target. And it's just easy to
think that-- oh, well, that could be the egoic brain and the
classic psychedelics come in. They scramble up the activity. That's the entropic
brain action. And in terms of the
start/stop, the boundaries, that entropic action
spreads out the system. It doesn't shut it off. It spreads it out. ANDREW HUBERMAN: Dissolution? ROBIN CARHART-HARRIS: Yeah. And you were talking about
the headspace as well. So that fits. If it's more capacious, it fits. The big qualifier with
psychedelic therapy that people rightly bring
up is it doesn't last. That's the paradox of it. The paradox of ego dissolution. So the ego might go
away during the trip, and you have these
profound insights about the molecular continuity
and how we're all one and interconnected. And then you come
down, and however long later, the ego comes back,
but maybe with a vengeance. And sadly, things
can go awry when people haven't done the work. Perhaps haven't
done the integration work and maybe ego
defenses come back and it's not a pretty picture. ANDREW HUBERMAN: How often
do you see that in the trials that you do? What percentage of
people coming through do you think end up
with worse than they were before the trial? ROBIN CARHART-HARRIS: It's
very rare in the trials that we've done. Yeah. But you see defenses come back. So you do see people relapse. That's more-- if
you're pushing out to like three months plus
in something like treatment resistant depression,
that's more the rule than the exception sadly. People relapse. If their histories are
histories of chronic depression, then while you might give
them a window of wellness, sadly, it doesn't last. That's not to say that
it doesn't ever last. It does. And we have people who
are in our first treatment resistant depression
trial who are well to my knowledge
today, back at work doing fantastically well. But sadly, the majority have
relapsed, to my knowledge. ANDREW HUBERMAN: And need to
do more psychedelic journeys. ROBIN CARHART-HARRIS: Well, they
can't, because it's illegal. That's been the really
difficult situation that we've been up against. Is that we do a trial where
all of a sudden this schedule 1 drug becomes a
medicine in the trial, or at least an
experimental medicine. We give the treatment, it
works fantastically well, gives people a remission
that they've never really had for however long,
and then the trial ends and they're denied
that treatment. And worse still, if they
were to have that treatment, they would be
committing a crime. It's a sick joke in a way. But that's the situation
that we've been in. ANDREW HUBERMAN: And
that's a perfect segue for what I want to
talk about now, which is, what is the current
state of legality in terms of-- or the
progression towards legality. I'd also like to touch on
the role of, let's just say, incoming big pharma. There are a lot of start
up companies now trying to capitalize on
these discoveries that you and others have made. The landscape out there
is very unclear to me. Maybe I'll just call out
some silos as I see them and maybe we can draw
some bridges between them, if they exist. At the ground level,
not the grassroots, but at the ground level,
I look to laboratories like yours, Matthew
Johnson's, Roland Griffith's some laboratories at Stanford. Nolan Williams. Laboratories studying the
effects of psychedelics in human beings, so
not animal models, in terms of their clinical
application for the treatment of depression, anorexia. I now know fibromyalgia, trauma. Let's lump MDMA
in there as well, assuming that it all
works in equivalent way at the level of where the
legislature is taking things. OK. So labs using government
money, philanthropy, et cetera. Then there are the
therapists out there that are accessing
what we believe are clean sources of MDMA. Psilocybin, LSD to do this. They are doing it illegally. This is in the US or other
Western European countries, because, obviously, it's
going to differ by country. Who are administering
these things on the basis of what they're
reading in these studies that you all are publishing. But also expanding on
and experimenting hippie flips and combination drugs
and ketamine and et cetera. But let's leave ketamine out
right now because it's legal. But there's that. Then there's the-- I don't want to say
recreational/open market, black market. And here I want to
raise a flag to the fact that Dr. Peter Attia did
a terrific podcast on this recently in his own
podcast, The Drive. The fact that fentanyl--
lacing with fentanyl is now showing up in MDMA
and psychedelics that are purchased on the street. So serious caution
to those getting it from uncertain sources. And then you've got pharma. And then as an umbrella
for all of this, you've got the FDA and law
enforcement agencies, which currently say, this
stuff is illegal unless it's being used
in a clinical trial. Selling it or possessing
it can get you charged with a crime ranging from-- I don't want to say
because I don't know. But up to felonies. Right years in prison. So can't take it
through airports, don't get caught with it,
don't buy it, don't sell it kind of thing. So where are we going from
that picture of the silos? I know things are in
clinical trials now. Most people, including
myself, are not familiar with how the different
phases relate to the proximity to legality. Could you just give us the
landscape and touch on how long you think it will
be before the people that come through
your trials could then go get a prescription
for psilocybin or potentially buy
it without the risk from a reliable
source, one would hope, but without the risk of
getting thrown in jail. I used to live in
Oakland, California. My understanding-- and please
correct me if I'm wrong, folks. Don't trust this information
and get in trouble. My understanding
is that psilocybin is decriminalized in
Oakland, but that's not the same as being legal. So what is going on out there? ROBIN CARHART-HARRIS: Mhm. Wow. Well, so much. ANDREW HUBERMAN: Yeah. I just asked 55 questions. ROBIN CARHART-HARRIS: I know. ANDREW HUBERMAN: But feel free
to answer just a subset of them if you like. ROBIN CARHART-HARRIS: Yeah. Well, Oakland's a funny one. I live close to Oakland. There are head shops
in Oakland that might be selling cannabis and
cannabis-related paraphernalia that are selling
mushrooms as well. Psilocybin, mushrooms-- ANDREW HUBERMAN: That's a fact. ROBIN CARHART-HARRIS: --openly. Yeah. ANDREW HUBERMAN: That's a fact. I can verify that. ROBIN CARHART-HARRIS: OK. ANDREW HUBERMAN: I
haven't purchased them, but I've gone in and checked
it out, what's going on here. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Yeah. ROBIN CARHART-HARRIS: Yeah. So the police aren't
going to prioritize that activity, the purchasing
of those mushrooms as a crime now in Oakland because
of the decriminalization. So those head shops shouldn't
strictly be selling. Well, they shouldn't be selling. They won't have a
license to be selling. Licenses don't exist
yet for that here. But let's see whether
they get shut down. They probably
will, I don't know. But there's a church
in Oakland sort of say that they're selling and
it's part of religious rights. They're using that church
model as a loophole, the way that Native Americans
can use peyote and they have a more
genuine case, I think. Because there is
a history there. But they're trying to
kind of piggyback on that. Anyway, that's close to
where we are right now. But federally, which is really
the major inflection point, is the FDA and the licensing
of psychedelics as medicines to be legally prescribed across
the country, across the US and beyond, that is close
because the key phase-- so there are different
phases of clinical trials, and the key one to know
about is phase III. Phase III trials are
licensing trials. If they're successful,
and typically you have to do at least
two successful ones, show the results to
the regulators who are the FDA, the medicine
regulators, and say, is this good enough now for
you to give me a license so that I can sell and provide
this medicine that we've demonstrated is a medicine. So that work has been
done with MDMA therapy for post-traumatic
stress disorder. MAPS have led that work and
done two phase III trials. I think they've already
publicly announced that the second
trial had results consistent with the first. We know the results
of the first, because they're published and
they were remarkably good. Something like 67%
remission rates. ANDREW HUBERMAN: And long term. My understanding is
some of those remission rates for trauma were years,
which is different than what you're describing
for psilocybin, where people might
need ongoing dosing. ROBIN CARHART-HARRIS: Yeah. That's true. Yeah. Yeah. ANDREW HUBERMAN:
But of course, just for trauma in those trials. My understanding is those
MDMA trials were not focused on depression. ROBIN CARHART-HARRIS: Yes. Yes. Focused on the trauma. So that's something,
because that data is being filed now, to my
knowledge, like as we speak. And they're anticipating
a decision maybe this year with rollout happening
as early as next year. I mean, that's
best case, I think. ANDREW HUBERMAN: Could I ask you
when you, when you say rollout, and it's the appropriate
term for MDMA, because of so-called rolling. About 20% of my
audience, maybe 50 will understand that not
funny joke that I made. Who's going to roll it out? Where would one get the
clean source of MDMA, meaning not laced with fentanyl,
not laced with methamphetamine, not undergone any
chemical conversion to some other drug which can
happen with extended shelf life, et cetera. Are people going to go to
their psychiatrist to get MDMA? And who's going to
be providing it? Is it going to be
some big major pharma? This seems like a
serious set of issues. ROBIN CARHART-HARRIS: Mhm. It is. And I don't have
all the answers. I do know that MAPS would be
providing, because they've done the work and they have
set themselves up in a sense to potentially
become the provider, whether as a pharma company,
which is the big question they're wrestling
with at the moment. It's very expensive to
become a pharma company. ANDREW HUBERMAN: And yet
they probably deserve to make the choice,
because they've put in so many years of hard
work when all of this stuff was considered like
raver culture party drug, they were the ones that spotted
the therapeutic potential. I mean, we knew there was
therapeutic potential based on work going back many
decades, but points to them, and I think in my opinion,
they should have the agency to make those decisions. ROBIN CARHART-HARRIS: Yeah. And it's such a remarkable
thing that's been achieved. And I think they've done it
all on philanthropic donations. I think so. Yeah. So there is this
big question mark. And the FDA are also
asking questions about, to your question,
who can provide this, because in the phase III
work and up until this point, there's been a MAPS training,
a MAPS therapist training. And you have to do this
formal training in order to be a practitioner
within the trials. But now, there's a
question from the FDA whether that MAPS training
can be the training that a clinician has to
have to now be a provider. And when I say rollout,
it's like offering this as a service, essentially. And so where would the
referral come from? That's a good question. That I'm not 100% on the answer. Whether it would have to come
from a psychiatrist or whether someone's-- sort of general physician
could do that referral. But they will be going
to a provider who is licensed and certified and
will have done some training. And there will be
a consensus on what constitutes good enough
training to provide. There will also be
some stipulations on the basic underlying
professionalism of the clinician who provides. So I imagine, they'll have to
be a mental health professional. I don't think they would have to
necessarily be a psychiatrist, they could be, I think,
a clinical psychologist. For all the dosings, I
think without question, there would have to be a
physician present or at least within ready access in
case of an emergency. ANDREW HUBERMAN:
Yeah, especially, with MDMA because of the
propensity for cardiac issues. ROBIN CARHART-HARRIS: Yeah. ANDREW HUBERMAN: Because of
the amphetamine properties. And where is psilocybin in
terms of the phase trials? Is it in phase II, phase III? ROBIN CARHART-HARRIS:
It's in phase III. There's psilocybin
therapy work being done for treatment
resistant depression by a company called Compass. Those trials which
are always multi-site. So there's always a bunch
of teams or labs in a sense. Geographically spread
out that are each contributing to data that
then gets matched together and is then submitted as part
of the phase III trial results. So that's happening
with Compass right now. It's psilocybin therapy for
treatment-resistant depression. Those trials have
just started and I think the earliest
estimate that I heard in a journalistic
article was because I don't think
Compass would say or they wouldn't say
publicly something like 2026. ANDREW HUBERMAN: '26. Wow. So MDMA is ahead of psilocybin. ROBIN CARHART-HARRIS: Oh, yeah. Yeah. It's quite a few years ahead. And it's more of,
not a certainty but it's very, very
strong position with MDMA. Whereas the work's
only just begun with psilocybin in terms
of the phase III trials. But then you have
this other situation of however many psychedelic
research centers there are now across the globe,
we had the first one in London in 2019. The first one in
2019, it's 2023 now, and I don't know
how many there are. But so much has happened in
such a small space of time. Yes. But all these
different indications I've been able to tell
you about-- anorexia and fibromyalgia syndrome. Trying to do a trial
with a colleague of mine at UCSF in methamphetamine
use disorder. He's got a trial going
on in Parkinson's disease and chronic lower back
pain and bipolar disorder. I mean, there's
so much going on. OCD. Almost the full gamut of
psychiatric disorders. Not schizophrenia, to my
knowledge, are being looked at. So there's so much
groundswell of activity. And I think these small
investigator-led studies, typically, they're small
because trials are expensive, are going to be reporting
positive results. I know what we're seeing. And it will be four-- let's see now, at
least four trials all with really positive results
in very difficult-to-treat disorders. And that's just us. And I know there's
so much elsewhere. Addiction disorders as well. Mike Johnson's work,
obviously, Michael Bogenschutz. So all this compelling
groundswell, it's really something. And yet the system
to really make a big breakthrough in terms of
licensing is, of course, slow. And that can frustrate people,
but it has to be done properly. ANDREW HUBERMAN: Yeah. Else we revert back to
what happened in the '70s where there was a lot of
interest in psychedelics. It's interesting to me. There was a close
juxtaposition of meditation and behavioral approaches to
self-directed state change and psychedelics. Meditation made it
through the hatch. I mean, there were
some years where it was considered counterculture
woo magic carpet weirdo stuff by Western science. But now, I mean, there are-- probably tens of
thousands is not an overstatement of
quality studies exploring how meditation can provide
advantages for the mind and even for mental health. And psychedelics
are now catching up, but they used to
be close cousins in the cultural framework. But the problem was,
I think, psychedelics were viewed as
making people crazy. And university professors
lost their jobs for having discussions
like the one that you and I are
having right now. And some people went to
jail, but mostly people either left academic
institutions or lost their jobs, whereas
now these are some of-- these studies of the
sort that you are doing and that are taking place
at Stanford and Hopkins and elsewhere are some of the
greatest magnetic pull for philanthropy
for universities. Donors are very
interested in supporting these sorts of studies, because
they and their family members and people they know suffer from
psychiatric illness for which the current big pharma
approaches simply have not worked. So it's interesting
to me that what once was seen as poison
is now being viewed as a potential therapeutic. It's not just
interesting, hopefully, it speaks to the evolution
of the human species. People seem to be coming more
open-minded about becoming more open-minded. ROBIN CARHART-HARRIS: Right. Yeah. That's a good one. Yeah. And yet-- yeah. There's so much that's
happening so fast. And there are elements of--
it's complexifying the space. There is critique, there's
been some bad practice in psychedelic therapy,
boundary crossing issues that have caused some scandals. ANDREW HUBERMAN: That's too bad. ROBIN CARHART-HARRIS: Isn't it? ANDREW HUBERMAN: Yeah. Well, I think too the
gene therapy, right? It just takes one bad incident. Gene therapy was on a fast
track three decades ago and then sadly, a child died
in a gene therapy trial. And it's like shut down
gene therapy practically for half a decade
and then it slowly started ratcheting up again. Gene therapy broadly
defined, and now we're in the age of potential
directed gene therapy using CRISPR and things
of that sort, which makes some people cringe and
other people very excited. If you have Huntington's
in your family, CRISPR is like the most
exciting technology ever, because you could potentially
eliminate it from your family line going forward, of course. ROBIN CARHART-HARRIS:
So I just really hope that we can be balanced
as this all plays out. Because it could go similar
way given the stigma, given the history that people would be
very twitchy with some isolated incidents. And overgeneralize them,
perhaps, in a sense, shining a light
on them, I think, is important that
has happened recently is important, because
it really drills home how important it is that
this work be done right and what the necessary
safeguards and standards should be. Yeah. And it won't be an
easy road forwards. But let's hope-- we've got
to hope that it succeeds, because current
treatments-- people talk about the mental health
crisis and to your point earlier about
anorexia rates, it's not always actually
the case when you look at the epidemiology. When you look at
the data that you see a big inflection
in diagnoses or cases of psychiatric illness. I would say, it's more-- the treatments haven't moved. They haven't really progressed. They haven't got any better
since the 1950s more or less. And new drugs have
been more of the same. So there haven't been
any paradigm shifts. And that's why I get
a little impassioned when I talk about psychedelic
therapy and that point that this is
something different. It's not a drug every day. That system, it's
not cutting it. Do we really want to
keep on with that system? Sure. Not everyone will want to trip. And that will
terrify some people so much that they'll
just want to be on their Lexapro or a
non-psychedelic, psychedelic, or whatever. And of course, it should be
allowed to have those options. Of course. And the more
options, the better. But I think there is great
value in really understanding what psychedelic therapy is. And I think when
you do, you realize that it is a major paradigm
challenge on many levels. And the fact that it's
different might be its greatest appeal at the moment, I think. ANDREW HUBERMAN:
Well, I am certainly grateful for your passion for
the potential for psychedelics to be added to the array
of potential treatments. And I really also appreciate
how much you put it in there alongside the other treatments. Maybe even in combination
with other treatments as opposed to saying,
this is the thing that's going to cure everything. And yet the passion
that you have for this potential paradigm
shift, the one that really appears to be happening at
the level of clinical data now is so important. So I want to extend
a voice of gratitude for that and for the
work that you're doing. I mean, I've been
outside of this field, but as a neuroscientist, I've
been paying careful attention to it really for the last
five, seven years or so. And it's abundantly
clear that it is a small group of individuals
who are really thinking in terms of how the
system works now and what needs to be
done in order to change the system for the
better like yourself that are really the driving
force behind this new movement or paradigm shift. That without question,
is going to lead to improvements in mental health
and physical health outcomes. So I just want to say
thank you for that. Also thank you so much for
joining us today to share this immense knowledge set about
the history of psychedelics. What they are, what they aren't. Their clinical applications
as seen in your laboratory and other laboratories. I'm sure people
already notice this, but you're incredibly generous
in terms of attribution and also in your
caution about explaining how some of the
results in particular, on anorexia, fibromyalgia, are
perhaps preliminary but very exciting. They're not published
yet, anyway. We wouldn't call
them preliminary. And also for touching
on mechanism. That is not just about people
feel better, but pointed to some potential
underlying mechanisms in terms of connectivity
changes and on and on. So thank you so much
for your time today. Thank you for the work
that you're doing. And thank you for the work
that is sure to continue. We will provide links to
studies in your laboratory, links to your laboratory
so people can learn more and support in the ways that
they deem appropriate for them. But just thank you,
thank you, thank you. Such important work
you're doing, Robin. ROBIN CARHART-HARRIS:
Thank you, Andrew. It's been a pleasure. ANDREW HUBERMAN: Thank
you for joining me today for my discussion with
Dr. Robin Carhart-Harris. I hope you found it to be as
informative about the science and clinical uses of
psychedelics as I did. If you'd like to learn more
about Dr. Carhart-Harris's research or support that
research or inquire into being a research subject in one
of his laboratory studies, please see the links in
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