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, we are
discussing psilocybin. Psilocybin is a psychedelic,
meaning it modifies the psyche. And in doing so, it changes
our level of consciousness. Psychedelics, such as
psilocybin changed the way that we perceive the outside
world and our internal world, our memories, our thoughts,
our feelings, et cetera. Not just while one is under
the influence of psilocybin, but it can also
fundamentally change all of those things afterwards
and for a very long period of time afterwards
as well, which is one of the
reasons why there's growing excitement about the
application of psilocybin and other psychedelics
for the treatment of various mental health
issues, such as depression, alcohol abuse disorder, and
addictions of various kinds, as well as things like
OCD and eating disorders. Today, we will
discuss psilocybin, talking about what it is. In fact, you may be surprised to
learn that psilocybin basically is serotonin. Now, for those of you that
are familiar with psilocybin and serotonin, you might
think, wait, that's not true. But, in fact, psilocybin main
effect is to mimic serotonin. But it does it in
a very specific way because it activates a subset
of serotonin receptors in a very strong fashion leading
to neuroplasticity at the level of the neural
circuits, that is the brain areas and the connections
that serve things like memory and perception. So if any of that is
confusing at this point, I promise to make it all
clear in just a few minutes. Psilocybin is one of many
psychedelics, of course. There are things like
LSD, DMT, 5-MeO-DMT. Even MDMA while not considered
a classic psychedelic is considered a psychedelic
in the general sense. Today's episode is going
to focus on psilocybin in particular. I will tell you
what psilocybin is, how it works at the
molecular and cellular level. I'll talk about how it
changes brain circuitry. I'll talk about the
clinical effects what's been demonstrated in
controlled laboratory studies. I'll talk about
dosages and translating from psilocybin mushrooms
to actual psilocybin, and the compound
that actually exerts the effects of psilocybin which
it turns out is not psilocybin, but something called psilocin. Psilocin is the
actual compound that goes into the brain to
create all the changes in consciousness and
all the rewiring effects that we associate
with psilocybin. So understanding how psilocybin
is converted to psilocin has tremendous impact on
the duration of a psilocybin journey, whether or not
that psilocybin journey is going to lead to a
short or longer window for neuroplasticity. In fact, many people
don't realize this. But much of the positive changes
that are possible with proper-- and I do want to underscore
proper psilocybin therapeutic approaches, takes place after
the session in which one feels all typical or
typically associated effects of psilocybin like
hallucinations and changes in thought patterns, et cetera. So today, we are going to talk
a little bit about chemistry. But I promise to make
it accessible to anyone and everyone, regardless
of whether or not you have a background
in chemistry or biology. We're going to talk
about some cell biology, the actual
neuronal changes that occur when one takes psilocybin. And we're going to talk about
how neural circuits change over time and how all of
that impacts the changes that most people are interested
in when they go on a psilocybin journey. Things such as long
standing improvements in mood, things such
as tremendous insight into themselves and to others,
into their past, their present, and their future,
and even changes in their levels of
creativity, or their ability to experience joy from
music or their ability to dissociate in a
positive way from things that formerly were depressing
or triggers for depression. In fact, we're going
to talk quite a lot about the conditions inside
of a psilocybin journey that make it actually
positive and therapeutic. This is a very important point
that I'll make several times throughout today's
episode, which is that just because
something invokes neuroplasticity changes
in brain circuitry does not mean that it's
therapeutic, or I should say, does not necessarily mean
that it's therapeutic. For neuroplasticity
to be therapeutic, it has to be adaptive,
it has to allow someone to function better in life
than they did previously. So today, we will talk about how
the conditions of a psilocybin journey, including
whether or not it's done with eyes
closed or eyes open, or whether or not people
alternate between eyes closed and eyes open
phases of that journey, as well as whether or not music
is played during that journey, and even what types
of music are played will dictate whether
or not somebody will feel better or worse in
the days and weeks and years following that psilocybin
journey, as well as the dosage level. Because as you'll
soon learn as well, there are clinical
studies showing that just one psilocybin journey
can improve mood in a long-standing way. But most clinical trials
involve two dosages spaced in very precise ways from
one another with appropriate follow up. But in both of those
particular journeys, the structure of the
journey who's present, who's not present,
eyes open or eyes closed, the particular
music that's played. All of those
features make up part of a larger
neuroplasticity trigger of which psilocybin is critical. But psilocybin is not
the only variable. So whether or not
you're interested in participating in a clinical
study, or whether or not you're interested in psilocybin
for other reasons, this is critical
information to understand. So today, we're going to talk
about nearly every feature of psilocybin possible,
including what psilocybin is, how it works at the level
of chemistry cell biology, and neural networks,
and neuroplasticity. We'll talk about the
clinical studies. We'll talk about dosages. We will talk about conditions
of clinical studies, and we will talk about the
post psilocybin journey period in which neuroplasticity
and the various activities, including therapy or
perhaps not therapy can contribute to positive
therapeutic changes from psilocybin. Now, as we go into
this discussion, I do want to underscore the fact
that at the time of recording this episode, meaning
now, May 2023, psilocybin is still
a Schedule I drug. It is considered illegal
in the United States. There's perhaps just
one exception to that, maybe a few others. But the main exception is
in the state of Oregon, psilocybin has been approved in
particular therapeutic settings for use in particular
conditions namely depression and some forms of addiction. So in Oregon, it's more
or less in the domain of a decriminalized as
opposed to actually legal. In other areas of the country,
including Oakland, California, there are some areas in which
it has been decriminalized. And perhaps there are a few
others that I'm not aware of. But, in general, psilocybin
and other psychedelics are still considered illegal. And this is very important. Not just saying
this to protect me, I'm saying this to protect you. Possessing or certainly
selling psilocybin, except for rare instances,
such as clinical studies and these decriminalized
areas that I talked about a moment ago is
still very much not allowed under the law. Today, I'll also
discuss safety issues. I'll talk about whether
or not young people, meaning people 25 or younger
should consider psilocybin given that their brain is
still in a rampant period of naturally occurring
neuroplasticity. I will also talk about
dosages as it relates to people who have
formerly been on or may currently be on different
forms of antidepressants. And I will talk
about people who are at risk for psychotic
episodes either because they know
they themselves have a propensity for psychosis
or they have close family members who have psychosis,
which includes things like schizophrenia, bipolar
depression, as well as things like borderline personality,
and some related psychiatric conditions. So today's episode really will
be a deep dive into psilocybin. So whether or not you
think you're already familiar with psilocybin
and its effects, or whether or not you're
just curious about them, I do encourage if you're willing
to try and ratchet through some of the understanding
of how psilocybin works and what it is,
leading up to some of the therapeutic applications
and different patterns of dosing spacing of
different sessions, et cetera. Because I do believe that
with that knowledge in hand, you will be able to
make far better, much more informed decisions
about whether or not psilocybin is right for you. 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
science related tools to the general public. In keeping with
that theme, I'd like to thank the sponsors
of today's podcast. Our first sponsor
is Eight Sleep. Eight Sleep makes smart mattress
covers with cooling, heating, and sleep tracking capacity. Now sleep is the foundation of
mental health, physical health, and performance. Everything goes far better
when we are sleeping well on a consistent basis. Now, one of the key things to
getting a great night's sleep is to make sure that the
temperature of your sleeping environment is correct. In fact, your body temperature
has to drop by 1 to 3 degrees in order to fall asleep
and stay deeply asleep. And waking up involves a
heating up of your body by about 1 to 3 degrees. With Eight Sleep, you
can program your mattress to be a specific temperature
at the beginning, middle, and towards the end
of your sleep night. Ever since I started sleeping
on an eight sleep mattress, I've slept far better
than I ever have. So it's an all around
great tool that has tremendous functionality,
not just for measuring, but for improving your sleep. If you'd like to
try Eight Sleep, you can go to
eightsleep.com/huberman and save $150 off
their pod three cover. Eight Sleep currently
ships in the USA, Canada, UK, select countries
in the EU, and Australia. Again, that's
eightsleep.com/huberman. Today's episode is also
brought to us by ROKA. ROKA makes eyeglasses
and sunglasses that are of the absolute
highest quality. Now, I've spent a lifetime
working on the biology of the visual system. And I can tell you that
your visual system has to contend with an enormous
number of challenges in order to make sure
that you can see clearly under any conditions. ROKA understands all of that
and is designed their eyeglasses and sunglasses so that
regardless of whether or not you're in a very brightly
lit area or a more shady area or you go from brightly
lit to shady areas, you can always see with
tremendous clarity. Now, even though they were
initially designed for sport, ROKA eyeglasses and sunglasses
come in a tremendous number of different aesthetics. So they have the what
I call cyborg versions that most people associate
with triathlon glasses and sports-related glasses. But they also have
a tremendous number of frames that you feel
perfectly comfortable wearing to work or out
to dinner, et cetera. If you'd like to try ROKA
eyeglasses and sunglasses, you can go to ROKA,
that's roka.com. And enter the code huberman to
save 20% off your first order. Again, that's ROKA, roka.com
and enter the code huberman at checkout. Today's episode is also brought
to us by HVMN Ketone-IQ. Ketone-IQ is a ketone supplement
that increases blood ketones. Now, I know most people are
familiar or at least have heard of the so-called ketogenic
diet, which is essentially a very low carbohydrate diet. It's designed to get your
brain and body functioning off ketones, which are a great
source of fuel for the body and brain. However, most people, including
myself are not ketogenic. That is I'm not
in a ketose state, pretty much ever
as far as I know. Nonetheless, with Ketone-IQ, you
can increase your blood ketones and thereby improve
things like cognition and physical performance. I find that when
taking Ketone-IQ, even if I'm eating a
standard omnivore diet, which is the diet that I follow,
by taking Ketone-IQ prior to workouts, sometimes
on an empty stomach, and especially prior to doing
any kind of cognitive work so researching podcasts, or
doing work related to my lab, or teaching, et cetera, that
I can maintain mental clarity for a longer period of time. And it does seem to enhance
my mental clarity as well. If you'd like to
try Ketone-IQ, you can go to hvmn.com and use
the code Huberman to get 20%. Off, again, that's hvmn.com,
and use the code huberman to get 20% off. Let's talk about psilocybin. And, again, today we're
going to focus specifically on psilocybin. And we're going to set aside
all the other psychedelics for future episodes. Psilocybin is what's
called a tryptamine. That refers to its
chemical composition, not to the so-called
psychedelic trip. In fact, it's
spelled differently. Tryptamine is T-R-Y-P.
Trip, T-R-I-P, of course. Tryptamines include
psilocybin, but also things like DMT and 5-MeO-DMT. The tryptamine
psychedelics very closely resemble serotonin itself. That's right. Most of you have probably heard
of the chemical serotonin. And serotonin is what's
called a neuromodulator, which means your brain and
body naturally make it, and that it modifies or changes
the activity of other neurons and neural circuits. And it does that generally by
either increasing or decreasing the activity of those
neural circuits. If I were to show you a picture
of the chemical structure of psilocybin or its
active derivative psilocin, and I were to also
put right alongside it an image of the chemical
structure of serotonin, provided that you weren't
a chemist who really likes to focus on the detailed
differences between things, you would say those
look very similar. And indeed, psilocybin in
its active form psilocin are very similar
structurally and chemically to serotonin itself. Now, as I mentioned before,
serotonin is something that you naturally make. And yes, it's true
that about 90% of the serotonin in
your brain and body is manufactured in your gut. However, contrary
to popular belief, the serotonin in your
brain is not manufactured from the serotonin in your gut. You have separate independent
sources of serotonin. That is you have
particular neurons that make serotonin in your brain. You also have
serotonin in your gut and those work more or less
in parallel separately. Now, what does serotonin do. This is really important
to understand because of the similarity
between psilocybin in its active form
psilocin and serotonin. Serotonin in that
it's a neuromodulator changes the activity
of other neurons and the net effects
of those changes are things that
you're familiar with. For instance, satiety or
the feeling that we've had enough of various
things, such as food, or a social interaction, or
sex, or pleasure of any kind. Serotonin is involved
in all of that. And an enormous number
of other things, such as mood regulation such
as our sense of pleasure itself, or lack of
pleasure, such as whether or not we feel motivated
or not motivated. It works in concert with
other neuromodulators, such as dopamine and
epinephrine and norepinephrine. In fact, if this were an
episode about serotonin, which it is not. You would soon
realize that serotonin is involved in so many
different functions that impact our daily life. And that is one reason
why certain antidepressant medications which alter
either increase or decrease the amount of serotonin
transmission in the brain will often have a
lot of side effects related to things like mood,
libido, appetite, sleep, et cetera. It's because
serotonin is involved in so many different things. And serotonin is involved
in so many different things because there are a lot of
different so-called serotonin receptors. Serotonin is a chemical
that we call a ligand. And the chemical
ligand is simply the thing that plugs into the
receptor for that chemical or ligand. The receptors, in this
case, serotonin receptors, have the opportunity to do
all sorts of different things. They can change the activity
of neurons making them more active or less active. They can cause growth factors
to be released making sure that those neurons
reinforce or even build up stronger connections
so that they're more likely to be
active in the future. Serotonin binding to
particular receptors can even change the gene
expression in particular cells making those cells proliferate. So make more of them. Making those cells more
robust, making those cells interact with new elements
of the brain and body. Basically, serotonin and all
these different receptors that it binds to has dozens,
if not hundreds, and maybe even thousands of
different functions. So the fact that psilocybin
so closely resembles serotonin leads to a very
important question that we should all be asking
ourselves, which is, why is it that psilocybin, which looks
so much like serotonin when one takes it in the form
of magic mushrooms, or some other form, maybe the
synthetic form of psilocybin itself, which nowadays is
manufactured in laboratories and placed in different
psilocybin containing foods and pills, et cetera. Why that leads to complex
yet fairly circumscribed sets of experience like visual
and auditory hallucinations, changes in particular
thought patterns, and neuroplasticity
that, in many cases, in the clinical setting provided
things are done correctly. Improvements in mood,
relief from depression, relief from various compulsive
disorders, et cetera. All right. This is really what
you need to understand if you want to understand
psilocybin, and how it works, and how to make
it work optimally for a given condition or goal. You have to understand
what it's actually doing and what allows psilocybin
to do fairly specific things in comparison to serotonin. Even though psilocybin and
serotonin are so similar is that psilocybin mainly
binds to and activates the so-called serotonin
to a receptor. The serotonin to
receptors is one of, again, many different
serotonin receptors. But serotonin 2A is expressed
in particular areas of the brain and even on particular areas
of neurons in the brain that allow for very specific types
of changes in neural circuitry to take place, not
just when one is under the influence
of psilocybin, but afterwards as well. So really in order to
have a useful discussion about psilocybin, we need to
talk a lot about the serotonin to a receptor. But fortunately for
you, unless you're somebody really interested
in structural biology or cell biology, that
discussion is not going to be about the binding pocket
for serotonin on serotonin 2A receptor, or a lot of
the downstream signaling of the serotonin to a receptor. We'll talk a little bit about
that where it's relevant. But more importantly, at least
for sake of today's discussion, we're going to talk about
how the serotonin 2A receptors really the one
responsible for triggering all the changes in
neural circuitry that lead to the changes, that
is the improvements in mood, the relief from compulsive
disorders in many cases, but really it's the serotonin
2A receptor selectivity of psilocybin that is
leading to all the excitement that you hear about
in terms of psilocybin as a therapeutic tool. Let me say that from a
slightly different angle. There are data that I'll
talk about today, which show that one,
although in most cases, two psilocybin journeys
done with particular dosages of psilocybin lead
to maximal binding or occupancy of those
serotonin 2A receptors in ways that lead to significant
and unprecedented relief for major depression. In fact, you'll soon learn
that the clinical trials for psilocybin are
outperforming standard therapy and outperforming
so-called SSRIs and various other
antidepressants in terms of providing depression
relief in ways that are frankly staggering not just to me, but
to the psychiatric community at large. And this is where so much of
the excitement is coming from. Now that statement
could be taken one way, which is to
just say, OK, well, here's a compound psilocybin
that outperforms SSRIs. And, therefore,
all the attention should be on psilocybin. But SSRI stands for Selective
Serotonin Reuptake Inhibitor. In other words,
the SSRIs of which there is now a lot
of controversy things like Prozac, Zoloft, et cetera-- I'm sure you've heard
some of this controversy. There are people who are
very pro SSRIs although there are a growing number of
people who really feel that the SSRIs are probably
most appropriate for things like obsessive compulsive
disorder where they, in fact, can be very beneficial. But there is a lot of
leaning back from SSRIs as the be all end all for
the treatment of depression nowadays because of the
side effect profiles. And the fact that it's
not even really clear that serotonin deficiencies are
the major cause of depression in the first place. Now, again, we're talking about
psilocybin not about SSRIs, but you should be
thinking, wait, how is it that two
molecules psilocybin and some particular
SSRI both of which look like and/or
increase serotonin transmission in the brain are
leading to either incredibly positive and
interesting outcomes or to troubling side
effect riddled outcomes? And, again, it all
boils back down to the selectivity
of psilocybin to bind that serotonin to a receptor. And so in order to understand
how psilocybin works and in order to understand
proper dosing profiles and spacing of sessions
a.k.a. journeys, we really need to talk a little
bit more about the serotonin to a receptor, where it is in
the brain, what sorts of things happen when psilocybin binds
the serotonin to a receptor, and how those things
set in motion, the various changes,
the neuroplasticity that allows people to feel
better in terms of their mood, and as you'll soon
learn, can experience more pleasure and joy from
things like music and enhanced creativity. All the things that I do
believe whether or not people are thinking about or
maybe even exploring psilocybin for recreational or therapeutic
purposes, all the things that people want and
are really talking about and perhaps even doing
psilocybin in order to obtain. So before going
any further, I just want to place an
image in your mind. You can place an image in your
mind whereby when serotonin is released in the
brain naturally not having taken any
compound, any drug, anything. It's getting released a
lot of different sites binding to a lot of different
serotonin receptors, doing a lot of different things. When somebody takes an
SSRI, the net effect of that selective serotonin
reuptake inhibitor is that there's more serotonin
around to exert its effects. Because it's a
reuptake inhibitor at the synapse, the
connections between neurons, the serotonin can do its
thing more extensively and for longer periods of time. But it's doing it
non-specifically. So when you think about standard
antidepressant treatments, at least for sake
of this discussion, you think of a sprinkling
or a spraying of serotonin at different locations
in the brain and binding to lots of different receptors. Whereas when you think
about psilocybin, even though the subjective
effects are pretty diverse, we'll talk about those in a
few moments, what you're really talking about is a
molecule of psilocybin that looks a lot
like serotonin that is selectively and very
strongly binding to and activating that
serotonin to a receptor. So that's the image I'd like
you to embed in your mind. And then the next image I'd
like you to embed in your mind is where these
serotonin 2A receptors are located in the brain. Now, the serotonin 2A
receptors are located in multiple brain regions. But they have a tremendous
amount of expression in the so-called neocortex,
the outside of the brain that includes things like our
prefrontal cortex, which is involved in understanding
context, which behaviors, thoughts, and
speech patterns are appropriate for
certain circumstances, how to switch context and
category switch when you go from playing sports, to
hanging out with friends, to being in a
professional setting. You change your behavior
in the way that you speak and perhaps even the
way that you think. You might think some things
that are out of context. But you probably keep
those to yourself. And your ability to
keep those to yourself are dependent on a
functional prefrontal cortex. There are a lot of 5-HT2A. And by the way 5-HT is the
abbreviation for serotonin. So there are a lot of
serotonin 2 receptors in the prefrontal cortex,
also in other areas of the cortex that
are associated with sensation and perception. That is hearing of sounds, that
is seeing of particular things. And in particular, there
is a very, very, very high expression of serotonin 2A
receptors in the visual cortex. And that is one of the
reasons why psilocybin triggers visual hallucinations. And provided
psilocybin is present at sufficient enough
concentration that is taken at a
sufficient dosage, one will experience profound visual
hallucinations regardless of whether or not their eyes are
open or their eyes are closed. Now, that's an important
fact because it explains one of the major
effects of psilocybin that people experience
while they are on the drug. Now, as I'll talk about
a little bit later in terms of what constitutes
a useful psilocybin session, useful meaning that
it's leading to adaptive improvements in mood, adaptive
improvements in creativity, in cognition, et cetera, is that
people not have their eyes open for at least the majority
of the psilocybin session, this is something I've discussed
with several experts who are running clinical
studies on psilocybin in their laboratories,
some of whom are going to be guests
on the Huberman Lab podcast in upcoming episodes, Again, I can't
underscore this enough. Because your visual
cortex contains so many of these
serotonin 2A receptors, and because psilocybin binds
so strongly to that serotonin to a receptor, you're
going to experience a lot of visual
hallucinations when you are under the
influence of psilocybin. There's no surprise there. This has been known
for hundreds, if not, thousands of years. It's one of the main reasons
why people take psilocybin. However, as I mentioned
earlier, these hallucinations occur even when the
eyes are closed. And it's now fairly
well-established that if people are to
take psilocybin and have their eyes open, much
of their cognition, much of their thinking,
much of the time spent in that psilocybin
journey is focused on the altered
perceptions of things in the outside environment. Sometimes this looks like a
fracturing of the outside world into geometric shapes. Sometimes it
appears as a melting of things in the
visual environment, including people's faces or
a morphing of people's faces. All of that has a
strong let's just call it a draw for
a lot of people who are looking for a
highly unusual experience inside of the
psilocybin journey. But I think if one's goal is
to derive long-lasting benefit from the psilocybin
experience, it's very clear that having an eye
mask or some other eye covering or something that ensures
that one's eyes are closed for the majority, if not, the
entire psilocybin session is going to be very
useful because it's going to limit the extent
to which one is focused on those outside changes
in visual perception a.k.a. hallucinations and rather
will allow the person to go inward to combine
whatever it is that they happen to be seeing in their mind's
eye with the different thoughts and memories and changes
in their emotions that are occurring. And that going inward by
staying in the eye mask, at least for the
majority of the time, seems to be a very, if
not, the critical feature of making the psilocybin
journey effective in the therapeutic sense. Now once again, I want to cue to
some of the safety precautions here. I'm going to say this at least
three times throughout today's episode. As I'm talking now and
various other times throughout today's episode,
you may get the impression that I'm all for everybody
doing psilocybin. And that is simply not the case. In order for a
psilocybin journey to be therapeutically useful, it
does require certain conditions and supports. And there are certain people
for which psilocybin use is going to be
contraindicated, meaning they should not do psilocybin. In particular, people
who have existing or have a predisposition to psychotic
episodes or bipolar episodes, even having a first
relative who has bipolar, or schizophrenic, or
schizotypal issues can be a rule out condition,
that is can get someone eliminated from a clinical
study on psilocybin for fear of triggering
psychotic episodes, not just during the
psilocybin journey, but potentially in
a long standing way. So, again, that's
really critical. The other thing
is that everything I'm talking about today
unless I say otherwise is really focused on
adults, meaning people who are 25 years old or older. That is their basic wiring
and rewiring of the brain that we call developmental
neuroplasticity is completed. All right. Most of the studies
today that I'll talk about involve subjects
ranging from 25 years of age out to about 70 years of
age, but no one younger. So, again, psilocybin
and its use is certainly not for everybody. It's still illegal, it's being
used in the clinical setting and research setting. There are these pockets
of decriminalized areas, and potentially soon
legalization of psilocybin, but again only in the
proper clinical setting. OK. Again, I say that not
just to protect myself, but I say that also
to protect all of you. Psilocybin is a
powerful, powerful drug. Not just to be under
the influence of, but also in terms of its
long-standing changes after the effects of
psilocybin have worn off. I'd like to take a quick
break and acknowledge one of our sponsors,
Athletic Greens. Athletic Greens now called AG1
is a vitamin mineral probiotic drink that covers all of your
foundational nutritional needs. I've been taking Athletic
Greens since 2012. So I'm delighted that they're
sponsoring the podcast. The reason I started taking
Athletic Greens and the reason I still take Athletic Greens,
once or usually twice a day, is that it gets
me the probiotics that I need for gut health. Our gut is very important. It's populated by
gut microbiota that communicate with the brain, the
immune system, and basically all the biological
systems of our body to strongly impact our
immediate and long-term health. And those probiotics
and Athletic Greens are optimal and vital
for microbiotic health. In addition, Athletic
Greens contains a number of adaptogens,
vitamins, and minerals that make sure that all of my
foundational nutritional needs are met. And it tastes great. If you'd like to
try Athletic Greens, you can go to
athleticgreens.com/huberman. And they'll give you
five free travel packs that make it really easy to mix
up Athletic Greens while you're on the road, in the car,
on the plane, et cetera. And they'll give you a year's
supply of vitamin D3 K2. Again, that's
athleticgreens.com/huberman to get the five free travel
packs and the year supply of vitamin D3 K2. Let's talk a little bit
about dosing of psilocybin and also about
microdosing of psilocybin. Now, this is an area that I
wouldn't say is controversial, but that there's how
should we say this. There's a lot of
loose thinking around this in the non-clinical
non-research communities. But within the clinical
and research communities, there is a lot of
data that's come out indicating what effective
and safe doses provided all other things
are considered safe. Safe doses of
psilocybin actually are. And here, we really can go back
to our discussion of psilocybin as quote-unquote magic
mushrooms or mushrooms. And if one were to
translate from the mushroom form of psilocybin to the
psilocybin that's actually used in various studies--
because frankly, in these studies, people
aren't eating mushrooms. They're typically taking
synthetic psilocybin either intravenously injected
into a vein or orally. And that's how the researchers
are able to tightly control the amount of psilocybin. And the typical dosage that's
used in clinical studies ranges from 1 milligram
often given repeatedly from day-to-day over
long periods of time, so-called microdosing. And really that 1 milligram
per day or even up to 3 milligrams per day
repeatedly over time is what people generally
think of as microdosing. As compared to say a
10-milligram dose given once, maybe twice in two separate
sessions, or a 25 to 30 milligram dosage that's
given once or twice. Now, those amounts of 1 to 3
milligrams or 10 milligrams, or 25 to 30 milligrams
might not mean much to those of
you that don't think about these things in
the research terms. Perhaps, you've
heard of microdosing and you've also heard of macro
or quote-unquote heroic dosing. OK. That's common or I should
say popular nomenclature for psychedelics. And I'll circle back to
that in a few minutes. But I think one of the
questions that I hear a lot is, how much psilocybin is present
in a given amount of mushrooms? And so the way this
typically works is that mushrooms are often
discussed in terms of grams, or ounces. So an 1/8 of mushrooms
refers to an 1/8 of an ounce of mushrooms, or x
number of grams of mushrooms. The breakdown is
actually quite simple. 1000 milligrams equals 1 gram. And the concentration
of psilocybin in most so-called magic
mushrooms is about 1%. So 1 gram of mushrooms
being 1000 milligrams means that it contains
approximately. And, again, it's approximately
10 milligrams of psilocybin. And in most of the
clinical studies, it's been shown that the
dosage of 25 to 30mg given-- or I should say,
taken once or twice-- and we'll talk about the spacing
of sessions a little bit later, taken once or twice is what's
leading to the most pronounced therapeutic outcomes. But, of course, with enhanced
therapeutic outcomes, one also observes enhanced
side effect profiles or what are called adverse events. So there's an important
nuanced conversation that has to take place. But right now, we're talking
about the conversion of grams of mushrooms to psilocybin. So 1 gram of mushrooms being
1000 milligrams containing 1% psilocybin means
that it contains 10 milligrams of psilocybin. Now, the so-called heroic
doses that you've heard about. And this is something
that's discussed. More with the let's call
them traditional or classic Psychonauts. These are people that may
have an advanced degree, but typically are not
running laboratories exploring the
effects of psilocybin in controlled clinical trials. These are people who have been
long time explorers, and often writers, and people
who have been spokespeople for psilocybin
and other psychedelics. And they will often refer to
the so-called heroic doses. It's a little bit
hard to translate from that informal community
to the scientific data. But in discussing that topic
with various researchers who run laboratories at
major universities focused on psychedelic
therapies, what I was told is that the quote-unquote
heroic dose that's often discussed really
refers to a 5-gram or so dose of mushrooms. So what that translates to is
50 milligrams of psilocybin. So when you hear someone talk
about a quote-unquote heroic dose, they're probably
referring to ingestion of 50 milligrams or
so of psilocybin, but in its mushroom form. So about 5 grams of mushrooms. And, again, it's
important to point out that the concentration
of psilocybin in different
strains of mushrooms and in different
batches, and depending on the age of those mushrooms,
and how they've been stored, et cetera, can vary tremendously
from batch to batch. In fact, there are
some laboratories that have explored the range
of psilocybin concentration in different mushroom strains
and different so-called magic mushrooms. And that range is pretty broad. It's anywhere from 1/2%
all the way up to 2%. What that means is
that someone might get a hold of 1 gram of
mushrooms thinking that they're taking 10 milligrams
of psilocybin in those mushrooms when,
in fact, they're actually taking 20. Or somebody could take 3
grams of mushrooms thinking they're taking 30
grams of psilocybin and in fact they're
only taking 10 or 15 milligrams of psilocybin. So the sourcing is
really key obviously as things become more legal, and
more regulated, and more used in the therapeutic setting. And this is what's
happening more and more. Or as people start to rely on
synthetically made psilocybin as opposed to using mushrooms
to ingest psilocybin. Then certainly,
the dosage thing is going to be more consistent
from batch to batch because we're not talking
about batches of mushrooms, we're talking about batches
of psilocybin itself. So now, I'd like
to take a step back from all this chemistry
and cell biology and talk a little bit about
the structure of a psilocybin journey itself and relate
that to what we now know about what's
happening in the brain during the psilocybin journey. And then a little bit later, we
will return to that serotonin to a receptor. When we talk about some of the
more lasting changes in brain chemistry and brain wiring,
that occur after the psilocybin journey is over. So let's take a
couple of minutes and just discuss the
various components of an effective therapeutic
psilocybin journey. And here I'm not
detailing a menu of things that people should do in
order to pretend that they are a psilocybin assisted
therapy coach, or to do self-administered
psilocybin therapy. That is not what I'm doing. What I am trying to do
is to share with you the consistent
components that are present in the clinical
trials that have demonstrated the effectiveness of psilocybin
for the treatment of depression and for other compulsive
and addictive disorders. And those data, meaning
the specific data related to those trials and
the references themselves, we'll get into a
little bit later. But we can't really have a
conversation about psilocybin and what it does without
talking about the so-called set and setting as it's
often referred to. That is known to at least bias
the probability of the journey being beneficial and not
a so-called bad trip. So what are the variables that
make up an effective and safe psilocybin journey? And, again, when
we say safe we're referring to people who are not
prone to psychotic episodes, that don't even have a
first relative that's prone to psychotic episodes. We're talking about people
that are 25 years or older. We're talking about people
that, for instance, are not taking antidepressants that
impact the serotonin system. This is very important
to understand. I think a lot of
people don't know this. But as far as I know,
all of the studies that have explored
psilocybin for its ability to positively impact brain
chemistry and mood and function have required that
people either not be on or abstain from
antidepressants in the weeks leading up to the
psilocybin journey. Now, that is not to say
that if you are currently taking SSRIs or something
similar that you should cease taking them
and do psilocybin, I'm absolutely not saying
that could be very, very, very dangerous if not catastrophic. Anytime you're going to
take anything or stop taking anything for
that matter, you do need to consult
with your physician. In this case, a
psychiatrist as well. So let's talk about
psilocybin journeys from the subjective side and
from the structural side. And when I say the
structural side, what I mean is what is a psychedelic
journey actually include? And here are the
words set and setting become extremely important. Some of you may have heard
that set and setting are the foundation of a well done or
even therapeutically beneficial psychedelic journey. And all of that really hinges
on safety and outcomes. So set refers to mindset. The mindset of the person
taking the psychedelic. And setting refers to-- as the name
suggests, the setting in which they're taking
it in and the people that are present there. So let's talk about
setting first. The setting for a
psychedelic journey needs to be one in
which the person under the influence of the
psilocybin or other psychedelic is safe. That means no windows
they can jump out of, that means no streets of moving
cars, they can run out into. That means no opportunity
for getting lost. That means no opportunity for
getting into bodies of water. In other words, it requires
that there be at least one, and perhaps even two or
more other individuals who are not also taking
psychedelics who are not also taking psychedelics present
in that setting to ensure that the person
taking the psilocybin is not going to harm
themselves or others. I say this not to sound
like a school teacher, even though technically
I'm a school teacher, but because, of course, I don't
want anyone to get harmed. And I'm also aware that there's
a lot of interest nowadays in psychedelics, such
as psilocybin becoming legal or decriminalized for
their therapeutic applications. And if we look back to the
late 1960s and early 1970s when the Controlled
Substances Act was invoked to make psychedelics
like psilocybin illegal, one of the bases for
that was not just the geopolitical
unrest at the time and things like the
Vietnam War, but also some highlighted instances
in which people did not take set and setting
into consideration, took things like LSD, stared
at the sun, went blind. Or took psilocybin, went out,
and harmed somebody else. Again, these are very,
very isolated instances. But these are the
exact instances that lead to
criminalization or the fact that things like psilocybin, and
LSD, and MDMA for that matter are considered illegal. Again, I completely
acknowledge that there are a number of different
factors making them illegal. We could have a whole
discussion about that. We talk about the drug
trade, the war on drugs. But right now, it's such a
critical time in the history and the use of psychedelics for
therapeutic and other reasons. And getting setting correct,
meaning making it absolutely as safe as possible for the
person taking the psychedelic is absolutely key. And one of the best ways
to ensure that it's safe is to have responsible
individuals who are not under the
influence of psychedelics present in that environment. So that's one
component of setting. The other component of
setting that we talked about earlier, which turns
out to be very important is the opportunity
and perhaps even the bias toward the person
on the psychedelic being seated or ideally lying down
and being in the eye mask or at least having
their eyes covered so that they can combine
any spontaneous visual hallucinations that occur
with the various thought processes that are
occurring while under the influence
of psychedelics. This is far and away different
than quote-unquote taking mushrooms and going
into the woods or taking mushrooms
and going to the beach. What we're talking
about today is the use of psychedelics for particular
brain rewiring outcomes that yes can involve things
like changing one's relationship to nature, or changing one's
relationship to somebody else by interacting with
nature or somebody else. And while I'm not trying to
diminish the potential value of those sorts of
psychedelic journeys, if we look at the scientific
data, the vast majority of it, not just in the
clinical setting, but in terms of understanding
the safety, and efficacy, and positive rewiring
of brain circuitry, that allows people
to feel better to understand themselves better
and to interact with life in more adaptive
ways going forward out of the psychedelic
journey involve these very, let's say, subdued settings
that are typically in one room, a closed environment with
one or two other individuals acting as guides or
helping the individual by talking to them from time
to time if they feel like they have to sort through
a particular aspect of the psychedelic journey
that's creating anxiety. And we'll talk about the contour
of the psychedelic journey that almost everyone
who takes psilocybin at somewhere between 20
and 30 milligram dosages tends to experience. But the setting
that I'm describing is not just a list of things
to make sure you're safe, but they're really
the list of things that also ensure that one can
get the maximum benefit out of the psilocybin journey. Now, other things included in
setting that are known, again, from scientific literature to
be very influential in terms of the experience that
one has and to bias things towards a
positive experience are, again, safety, eye mask,
but also the presence of music. Now, when I first heard about
this from one of the Premier researchers on psilocybin
and other psychedelics which is Robin Carhart-Harris,
he's a professor at University of California
San Francisco, who's one of the major pioneers in
the studies of psychedelics. And when he first
started telling me about the critical
role that music plays, I thought, OK, that
makes sense you know. Music can impact our emotion,
impact the way that we think, and could, therefore,
impact what one experiences during the psychedelic journey. But he really underscored for
me the extent to which music is not just an incidental
feature of the setting in psychedelic set and
setting, but that it is one of the major drivers
of the actual cognitive and emotional experience
that somebody has on something like psilocybin
that allows the psilocybin journey to be looked at or
viewed, not just as beneficial, but, and this is quoted in the
scientific literature as one of the most profound and
important positive experiences that one ever experienced
in their life. So let's talk about
the sorts of music that have been used in
these clinical studies. Well, first of all,
we need to think about how long the psilocybin
journey itself is going to be. And the typical duration
of the psilocybin journey is anywhere from 4 to 6 hours. It's going to depend
somewhat on dose. It's going to depend somewhat
on variability in people's liver metabolism, and it's also
going to depend somewhat on how much food people
have in their gut. In all the clinical
studies that I read, it was advised that people
not have any food in their gut at the time in which
they ingest or are injected with the psilocybin. That's particularly
true if people are going to be taking
psilocybin, mushrooms, in order to get their psilocybin. And that has been
done in a few studies. Most studies however
use synthetic psilocybin taken orally. Again, that's converted
to psilocin in the gut by the acidity of the gut. And the acidity of
the gut is going to be impacted by the various
foods that people eat. And so that's one of the major
reasons why people are advised to not eat for at
least four hours prior to the psilocybin journey. So here we've got this 6
hour, what we're calling, journey because that's what
everyone calls it or trip. That people start experiencing
about 30 to 45 minutes after ingesting psilocybin
or taking psilocybin. There's a peak component
in which there's a maximal intensity of
emotion and often that's also associated with anxiety. And this is very
important to understand. The anxiety component
is part of what in the therapeutic setting, they
refer to as ego dissolution. And that anxiety
around the peak-- and I think most people would
probably hear peak experience and think, oh, we're talking
about a peak positive experience. But no, we're referring to a
peak experience and anxiety that people stay with and
then come down from gradually as one goes from the
second or third hour after taking psilocybin. And that tapers off slowly
toward the 6-hour mark what, sometimes people refer
to as parachuting back in. Of course, hopefully,
I would very much hope people aren't
actually parachuting back in while on psilocybin. But I think you get the idea. The music that's typically
played in the clinical studies using psilocybin for the
treatment of depression, or for compulsive
disorders, or addiction tends to have a
particular contour that matches with and can also drive
that contour of the psilocybin journey that I just described. Again, we're
talking about people wearing an eye mask
with guides present. So people who are not taking
psilocybin there as well to ensure that the person
feels supported and is safe. The person is typically
lying down, sometimes sitting down, but more often
than not lying down, wearing an eye mask-- and the music that's played at
the beginning of the psilocybin session tends to be
music that doesn't have a lot of vocalizations,
it tends to be things like classical music, it
tends to be fairly low volume. But then transitions into music
that has a lot of percussion. So often drums that
tends to be higher volume, that has a
lot of intensity. At about the time that one
would be experiencing the peak in emotion and perception, that
so-called peak of the journey. That intense music tends to
be played for about 45 minutes to 90 minutes, depending
on the study one looks at. And then tends to transition
into softer music, again. Sometimes choral type or more
melodic music, often female voices in particular,
and then transition into nature sounds and things
that more or less mimic the outside natural
world and less so synthetic things like drums, or
instruments, and vocalizations, and things of that sort. So why would it be so
important that music match and even contribute to
the subjective experience that people have
on psychedelics? And here, we should probably
take a couple of moments, and just talk about what those
subjective experiences are like. So for people that haven't done
psilocybin or any psychedelics, it's a little hard to describe. But one way to describe
it is that there's a lot of so-called
perceptual blending. So, for instance,
people in the eye mask will report seeing some
geometric shapes and colors. But perhaps the music
they're listening to will then start to change
the intensity or the movement of whatever it is
that they're seeing, hallucinating inside of the eye
mask in ways that are linked. This is referred
to as synesthesia or the merging of
different senses that are not ordinarily merged. In addition, people under
the influence of psilocybin or other psychedelics
for that matter often will report that
their pattern of breathing becomes linked to the
perceptions of things that they are hearing,
or seeing, or feeling. So, for instance, if they take
a big deep breath in and then a long exhale out, they may
find that during a long exhale out, that the notes
of music that they're hearing in those
moments are also drawn out for the duration of
the breath in they'll inhale and that they're getting
at least what they perceive as control over the
music which, of course, they are not
actually controlling by using their breath. And that perhaps their
visual perceptions are also being merged with that. So those are just a
couple of examples of how perceptual
blending a.k.a. synesthesia can occur
while under the influence of psilocybin. And this really is highly
individual from one person to the next. Some people, for
instance, will find that if they take their
fingertips and rub them across the couch or the
chair that they happen to be lying down or sitting
on, that they will experience a change in the music. Maybe even if they
move their hand up, they hear an increase
in frequency of sound. They move their hand
down, they hear a decrease in frequency of sound. And all of this is linked
to their emotional state at the same time and vice versa. So we're talking about a lot
of perceptual and emotional blending and some
sense of control over one's perceptions
and emotions in a way that's very
unordinary, even extraordinary. We can step back from all
of this very subjective description of the
psychedelic journey and ask, what is going on that would
allow these sorts of things to occur? And there you are already
equipped with an understanding of the cell biology
and the chemistry that makes all of this possible. And that is that when psilocybin
is ingested and then converted to psilocin, it's the psilocin
that crosses the blood brain barrier, and then
even though psilocin looks a lot like
serotonin, psilocin has this incredible ability
to predominantly activate the serotonin to a receptor. Well, we can understand
much of what's happening at a subjective level
during the psychedelic journey, even right down to
the sorts of emotions, and perceptual blending,
the synesthesia. We can understand a lot
of that by understanding where the serotonin 2A receptors
are expressed on neurons, and what those particular
neurons are doing. And the simplest
way to describe this is that there's a
category of neurons that we call pyramidal neurons. Pyramidal neurons are found
lots of places in the brain. But they're called
pyramidal neurons because they're sort of
shaped like a pyramid. They have a cell body, which
is the part of the cell that has the DNA in it and a lot
of other important things like the organelles,
mitochondria, et cetera. And then they also have
what are called dendrites. Dendrites are the little
branches or processes that reach out both from
the bottom of these cells. And then these
pyramidal cells are interesting because they also
grow a branch up, up, up, up, up into layers of neural
tissue above them. And they have what's
called an apical branch. That's the part that grows up. And then they fan
out at the top. And that fanning out
at the top allows them to communicate with other
neurons in their environment. So if you're not getting a good
picture of this in your mind from my description,
I apologize. But simply think about putting
your arms out to the side. And by doing that,
you're able to interact with things that are some
distance from your body, an obvious thing in that case. These cells are effectively
doing the same thing by extending little processes
out into layers above them and to the sides. And this is really
important because much of the serotonin to receptors
that are present on neurons in the brain are present
in those apical dendrites, those branches of
these pyramidal neurons that are above and
that extend out to the side of those neurons. And so when somebody is under
the influence of psilocybin, that means that psilocin
has bound to the receptors on those apical dendrites. And it's increasing
lateral communication across brain areas. In fact, this is
perhaps one of the most well-documented effects
of psilocybin and other psychedelics, which
is that there's a shift from the brain
being more modular, meaning more segmented
like auditory neurons are communicating electrically
and chemically largely with other auditory neurons. Of course, they'll communicate
with other types of neurons, too, right? When I hear something off to my
right, like a snap of a finger is off to the right,
I'll turn my head. And my ability to do that
depends on my auditory neurons being linked up with
things like my motor system and my visual system. But the key thing
to understand is that when there is psilocybin
present in one system, that the communication of any
of these pyramidal neurons, the ones involved in hearing,
the ones involved in thinking, the ones involved in
memory, the ones involved in visual perception
or in the generation of visual hallucinations
with eyes closed, those are all talking to many,
many more other neurons more extensively. So what happens
effectively is that there's a reduction in the modularity,
the separateness of function in the brain, and an
increase in what's called integration
of communication across what would otherwise
be disparate brain regions. We can say that really simply
by saying psilocybin increases communication across the brain. Now, in addition
to that, there's a reduction in what's called
the hierarchical organization of the brain. Typically sensory
information comes in from the outside environment. So we hear something, we see
something, we taste something, we smell something. And in what's called a bottom
up fashion meaning bottom from the periphery up,
meaning it propagates up through the eyes, through
the nose, through the ears through the skin, or the
senses in those regions, I should say, up into
areas of the brain that sit deep to the cortex
like the thalamus. And then the thalamus
is a way station, it's like a
switchboard that sends visual stuff to
the visual centers, and auditory stuff to
the auditory centers, and touch stuff to
the touch centers, and things that maybe
trigger a memory off to the memory centers
of the brain, et cetera. That's the typical organization. It's hierarchical because
it goes from the periphery up to the more
complex processing regions of the brain
that make decisions, that link all of that stuff
to prior experience, maybe plans about the future. When psilocybin is
present in the system, there's a broadening of the
flow of that information from the bottom up as well. And that has to do with
what's called thalamic gating. The thalamus is a very
interesting structure. We probably don't want to go
into it in too much detail right now. But it really is
like a switchboard in a way station saying,
hey, pay attention to the visual
stuff, pay attention to the auditory stuff, or just
to the visual and auditory stuff, and ignore touch
sensation for the time being or vice versa. When psilocybin is
present in the system, and when serotonin 2A receptors
are activated very strongly, there's a tremendous broadening
of the flow of information up and through the thalamus. So not only is there
more communication of so-called higher
order brain centers, we refer to them as higher
order because they're involved in thinking, and
decision making, and emotion, et cetera. But there's also a shift in
the flow of sensory information into the brain
that can generally be described as broader
and including more blending of the different senses. And when I say
blending of the senses, I'm also referring to blending
of the sense of interoception of our sense of
our body and what's happening inside of our body. And this without
question, at least partially explains when under
the influence of psilocybin, one's breathing can
be linked to a sound, and then suddenly
the sound one thinks is being controlled
by one's breathing, or that the sound itself can
be linked to something that we see in our mind's eye
while in the eye mask. Essentially, what
I'm describing here is that serotonin to
a receptor activation allows for more broad, less
precise, and less hierarchical activation of brain circuitry. And when I say
hierarchical, what I mean is that normally things go
from periphery, from eyes, to thalamus, to visual cortex. However, when under the
influence of psilocybin, as I mentioned before,
even in the eye mask, the visual cortex is
going to be very activated even in the absence
of any visual input. So then if one hears
a sound, perhaps from music, a particular
motif or voice, and that's linked to a
particular emotional state, that is now being blended with
visual phenomenon occurring within the brain that
have no external stimulus. And so while the
patterns of activation in the brain while under
the influence of psilocybin aren't random, they are far less
channeled, far less modular, and far less hierarchical than
would ever be the case when not under the
influence of psilocybin I'd like to just
take a brief break and thank one of our
sponsors, which is LMNT. LMNT is an electrolyte drink
that has everything you need and nothing you don't. That means plenty of
salt, sodium, magnesium, and potassium, the so-called
electrolytes and no sugar. Salt, magnesium,
and potassium, are critical to the function of
all the cells in your body, in particular, to the
function of your nerve cells, also called neurons. And we now know that
even slight reductions in electrolyte concentrations
or dehydration of the body can lead to deficits in
cognitive and physical performance. LMNT contains a science
backed electrolyte ratio of 1000 milligrams. That's 1 gram of sodium,
200 milligrams of potassium and 60 milligrams of magnesium. I typically drink LMNT
first thing in the morning when I wake up in order
to hydrate my body and make sure I have
enough electrolytes. And while I do any
physical training and after physical
training as well, especially if I've
been sweating a lot, and certainly, I drink
element in my water when I'm in the sauna and
after going in the sauna because that causes
quite a lot of sweating. If you'd like to try LMNT,
you can go to drink LMNT, that's L-M-N-T.com/Huberman to
claim a free LMNT sample pack with your purchase. Again, that's drink LMNT,
L-M-N-T.com/Huberman. Now in all fairness to
the scientific literature, there are not one,
not two, not three, but four prominent theories
of which brain networks are most activated
during a psilocybin or other psychedelic journey. And so for those of
you that are interested in those different models,
first of all, please know that they are
not competing models. While some of them disagree
about some of the details. It's very likely that all
of these models are true. They include things like changes
in the so-called default mode network. There's a lot of
interest in this. I've talked about it
before on this podcast. The default mode
network is the network in the brain that's
thought to be responsible for spontaneous imagination,
for daydreaming, and that reflects
the base activation state of the brain when
there's no drugs in our system. And the default mode network is
one of the systems or networks rather that is
thought to be required under conditions of psilocybin
or other psychedelics. Again, if you're
interested in these models and comparing and
contrasting them, there's a very nice review
from Brian Roth's Lab at Duke entitled, The Neural
Basis of Psychedelic Action. We'll provide a link to this
in the show note captions. And, again, I just
want to emphasize that all of these models
have been shown to be true in different studies. And what they all point to is
more extensive communication between areas of the brain
that normally are not as active at the same time
while under the influence of psychedelics,
such as psilocybin. The controversy in
the field relates to which of these networks is
the one that changes the most to explain the therapeutic
outcomes that have been discovered in recent years. So, again, check out that
review if you're interested and that sort of thing. In the meantime, we
can cut a broad swath through all of those
models, and just say that psilocybin
expands the functional connectivity of
the brain while one is under the influence
of psilocybin. And it does seem that some
of that expanded functional connectivity persists after
the effects of psilocybin have worn off. And that statement about
the functional connectivity of the brain being
more expanded, not just during the psilocybin
session, but after as well, has been substantiated
in a number of papers. But one of the key
papers in this area is one that I recommend
people check out if they're interested
in this sort of thing, is entitled, The Effects
of Psilocybin and MDMA on Between Network Resting
State Functional Connectivity in Healthy Volunteers. And I like this paper
for a number of reasons. First of all, it's a
very high-quality paper carried out in the laboratory
of Robin Carhart-Harris at UCSF. Again, one of the
Premier researchers in this area of psychedelics
and their function, what they do in
the brain, and also their therapeutic
applications, but also because it focused on
healthy volunteers. They explored using
brain imaging. What brain areas are
active in a resting state? So things like
default mode network. Then they had people
take psilocybin or MDMA. And then they looked
at the connectivity between those brain areas
in those same individuals when they were not under
the influence of these drugs and found more
extensive connectivity. All of which pointed to an
enhanced lateral connectivity, less hierarchical
organization effectively more interconnection
and communication between different brain areas. I think not only is the
fact that they looked at healthy volunteers very
interesting and important, but also that they looked
at this resting state of the brain. They weren't providing
a particular auditory or visual stimulus for
people to hear or look at while they were in the
brain imaging scanner as it's called rather,
they were simply looking at how the brain
was behaving at rest. And so it's very clear that
for people that do two or even just one of these psilocybin
journeys at a particular dose, that the brain is
actually getting rewired. We hear this a lot. Psilocybin or other
psychedelics lead to plasticity. They rewire your brain. Let's go back to what we
said at the beginning. Rewiring of the brain
is not the goal. Adaptive rewiring of the
brain is the goal, right? Rewiring that leads to new
ideas that are interesting, that are accessible after
the psychedelic journey. New ideas and new ways of
thinking or feeling that allow people to function
better in their lives. That's the goal of effective
psychedelic therapies. Not simply rewiring
of the brain. A brain injury for
that matter will lead to rewiring of the brain. But that's maladaptive rewiring. The use of things
like amphetamines or methamphetamines,
in particular, will lead to rewiring
of the brain. But that is strongly
maladaptive rewiring So now, there are really
dozens of studies conducted in humans using brain
imaging and other techniques have evaluated how
things like psilocybin change connectivity
in the brain. And I think the
take home message is it expands that connectivity. However, it seems
to do so in ways that still allow people to
function in their daily lives. And one of the key things that
I gleaned from the literature on the therapeutic
use of psilocybin for the treatment
of depression is that very seldom, do people
who take psilocybin experience long-term issues with memory. Why is that so critical? Well, you could imagine
that increasing connectivity in the brain
reducing modularity, reducing hierarchical
organization of the brain would lead to disruptions
in memory, right? It's as if you're shuffling
books on the bookshelf so to speak. But that doesn't
seem to be the case. Rather it seems that the
increase in connectivity is leading provided set
and setting are correct, provided safety
protocols are followed to positive rewiring or adaptive
rewiring of neural tissue. So that's one of the
things that makes psychedelics and
psilocybin, in particular, very exciting from the
therapeutic standpoint. And of course, we
have to acknowledge it's also it has a lot of people
excited about psychedelics, not just for the treatment
of depression, but for expanding the brain's
capabilities more generally. So along those lines,
I want to touch on the issues of creativity
and the experience of life outside of
psychedelic journeys is impacted by
psychedelic journeys. And here this relates to a
question that I heard a lot. When I put the call
out on social media that I was going to do this
episode, and I asked people, what do you want to
know about psilocybin? And one of the more common
questions that I got was, does it increase creativity? Does it increase our
experience of life in ways that are beneficial
aside from its now documented positive effects in
treating depression and compulsive
disorders and addiction? And the short answer
to this is yes. But that the positive
effects of psychedelics, psilocybin, in
particular, on creativity, and our experience
of life have only been explored in a fairly
narrow set of dimensions. However, where
it's been explored, there's some really
interesting findings. So one of the more
interesting findings I think is a paper entitled
increased low frequency brain responses to music
after psilocybin therapy for depression. I think this is a really
interesting paper. Because what the authors did is
they took advantage of the fact that in these therapeutic
psilocybin sessions that were carried out for
the treatment of depression, music is being played. And there are prior
studies showing that when music is played,
you activate different brain areas depending on what
music is being played. It's somewhat obvious perhaps. Sad music versus intense. You can think about heavy
metal, versus choir music, versus Gregorian chants,
versus punk rock music, and on, and on. It makes sense that
different brain areas would be activated when
different patterns of music are played. However, there do seem to
be some universal features of brain activation
in response to music. This should probably be the
topic of an entire episode of the Huberman Lab podcast. And indeed it will be. For instance, there are
areas of the auditory cortex that are activated. No surprise there. And areas of the brain's
reward circuitry, the so-called ventral striatum
and the so-called mesolimbic reward pathway. I talked a lot about these in
the episodes about dopamine that I've done previously. These are brain areas that
lead to the release of dopamine in other brain areas, and that
reinforce certain experiences, and that tend to give us the
subjective feeling of, yes, I like this. I want more. So in this particular
paper, what the authors did is they took
advantage of the fact that people are in the
clinic, they're on psilocybin, they're listening to music. And as you recall,
the music played at different stages of
the psilocybin journey are different. They have a different
emotional component. And music is a really nice
stimulus in the laboratory as we say. Because like with
visual stimuli, you can break it down into
high frequency, low frequency. Sounds like dum, dum, or ah, ah. These kinds of things
that was my attempt at low frequency versus high
frequency auditory stimuli. Or at the spatial frequency,
or what in the auditory domain would be called the
temporal frequency is it boom, boom, boom. Or is it boom, boom, boom, boom. All we've changed there
is the temporal frequency. The sound was somewhat
the same, but the distance between those sounds
was different. You get the idea. So they have access
to these people and these different conditions. And they can put them
in the brain scanner. And they can do that before and
after having taken psilocybin. And the long and
short of this study is that psilocybin changes one's
experience of music, not just during the psilocybin journey
itself, but thereafter. And, in fact, it changes
one's emotional response to music in very
interesting ways. For instance, one of
the more common features of major depression
is that people don't derive as much
pleasure from different types of experiences,
whether or not it's food, or sex, or social
experiences to the point where sometimes they just stop trying
to seek out those experiences. People with depression often
feel as if music no longer has the same impact. It just doesn't really
lift them up very much. This study found that people
who have taken psilocybin, according to the parameters
we talked about earlier, can get a return of the
elevated emotionality, the positive emotions associated
with music that formerly made them feel good. In other words, they
can feel music again. They can feel good in
response to music again. Now, this is interesting
because, in theory, it could be that psilocybin
simply allowed them to access the emotions
around music, again, more generally. But that's actually
not what this paper and some other papers that
have been published report. Rather, it seems that
taking psilocybin can increase one's positive
perception of music that one likes and can
tone down or reduce the depressiveness or
the sadness of music that tends to make one sad, even
after the psilocybin has worn off and for a long
period of time afterwards. Maybe even forever. Although no study, of course,
can be carried out forever because forever is forever. What we do know, however,
is that psilocybin can rewire the connections
between the emotion centers in the brain and the
networks that control auditory perception of music. And leads to this
condition in which people who felt like, I was depressed,
or I couldn't feel the music, I just wasn't getting the same
lift and joy from it again, they can start to experience
more joy from that music again. And that music that made
them feel sad and depressed has a diminished
capacity to make them feel sad and depressed. And there's a lot
of neuroimaging data in this paper that point to
the specific brain areas that include areas like the
ventral tegmental area that can explain why these sorts
of effects would occur. So this isn't just subjective
reports of people saying, oh, yeah, I was depressed. And music didn't feel really
good and now it feels great. Or that used to
make me feel so sad. And now, I feel like
I have a capacity to listen to that without being
crushed by feelings of sadness. The paper included
some subjective reports of that sort. But then was able to link those
to changes in brain circuitry and brain activation in response
to music using neuroimaging. So in that way, it really
points to both the subjective, and structural, and
functional changes that psilocybin can bring
about through that expanded connectivity
between brain areas. Because remember during
the psilocybin session, it's not as if music or
the perception of music is specifically being looked at
or focused on in these studies, rather music is playing. People are in the
eye mask, they're feeling all sorts of
things, they're breathing, they're hearing their touch. It's all happening all at once. There's a peak. It's long. There's a long taper. The music's changing. OK. All of that took place
in this study as well. But it is after the session
when comparing brain activation states to music of a
particular type, sad or happy. And comparing that to the
patterns of brain activation that occurred before
the psilocybin journey that they discover
that people's brains have rewired during
the psilocybin session in a way that allows
them to experience joy in response to music again. So that's one of the
more rigorous studies I was able to find. That addresses this question
of whether or not psilocybin really does rewire
the brain in ways that allows us to
be more creative and experienced life differently
after the psilocybin session. Now, that paper didn't focus
specifically on creativity. I did an entire
episode on creativity that talked about different
types of meditation, like open monitoring
meditation, it talked about different
patterns of thinking that one can actually practice
to increase creativity. We had arguably one of the most
creative people on the planet. Rick Rubin came on
this podcast talked about the creative process
from the perspective of music and his role in producing music. So you can check
out those episodes if you're interested in the
neural circuitry related to creativity. At least at the time of
recording this episode. There haven't been a lot of
studies looking specifically at the brain networks
that we think are involved in
creativity and how those change in response
to psilocybin and other psychedelics. I imagine those studies
are either happening now or will happen in the future. But the studies I just
described referring to the changes in emotionality
and responses to music, I think provide a nice
template for what's likely happening both
during psilocybin journeys and after those
psilocybin journeys. When we talk about less
hierarchical organization, more connectivity between brain
areas, what it's pointing to is the fact that during
the psilocybin journey, people have the
opportunity to learn new relationships between
different sensory and emotional states. And those new relationships
seem to persist long after the psychedelic
journey has been finished. And a lot of people
researching psilocybin in the clinical setting
think that that's one of the major reasons
why psilocybin and other psychedelics can rewire our
relationship to things more broadly. It allows for new learning,
new contingencies. And when we look at depression,
we often think diminished mood, people don't have an
appetite, they're not interested in social
relationships, or romantic relationships. They're really struggling. And all of that,
of course, is true. But another lens to look
at depression through is that a lot of that
thinking and a lot of those emotional
states that are negative are somewhat habitual. They relate to
implicit understanding and living out of the
idea that A leads to B leads to C. You seek
out a relationship, it doesn't work out. Try a new job, you
don't get the job. You get the job, it's no good. All these negative outcomes
of if A, then B, then C. And it does seem
that psilocybin can have this effect of invoking
new patterns of learning. New considerations about
what might be possible. And indeed, may even lead to
actual rewiring of the emotion centers in the brain with these
other brain areas and vice versa in ways that eject people
from the psilocybin session thinking, oh, yeah, I used to
feel this way about something, work, relationships,
myself, et cetera. But I'm willing to consider
this other possibility. Or this other possibility
seems at least partially true to the extent that I'm
willing to go out and evaluate that. Now, here I'm speaking
very subjectively. But remember, we have to tie
back the subjective experiences and changes of
things like music, and emotion, and our
relationship to life, and jobs, and relationships
back to the cell biology and chemistry of psilocybin. Because, ultimately, it
really is just a chemical activating receptors. Those receptors changing
networks in the brain. And the journey
itself seems to be the time when all of those
changes are put in motion. It's like a boulder
that gets rolling. In fact, I think the best
way to think about psilocybin and other psychedelics
is that they initiate the neuroplasticity
process, but they are not the neuroplasticity
process itself. And the journey itself is not
where all the neuroplasticity occurs. We know that for sure. In fact, if you
want to imagine how psilocybin and other
psychedelics work to change the brain,
think about them as a wedge that gets
underneath the boulder, that is the neuroplasticity
that gets rolling forward. And then think
about whether or not the plasticity is adaptive or
maladaptive, whether or not it actually serves you in
your life on a daily basis, or not, depending
on whether or not you're using your
conscious brain to move that Boulder in a
particular direction. Not just bulldozing through
things and destroying them, but clearing a path through
old ineffective maybe, even destructive patterns
of thoughts, or emotions, et cetera. I give you that
analogy because I think it more accurately
captures what psychedelics like psilocybin are doing. Rather than the typical
discussion around psychedelics that we tend
to hear which is that, oh, it creates plasticity. And plasticity is what you want. For the next couple
of minutes, I'd like to focus on some of
the key and stereotype that is characteristic experiences
that people tend to have during a psilocybin journey. Because there's some really
interesting research on this. These are phrases that
perhaps you've heard before. Things like letting
go, ego dissolution, feelings of connectedness. Well, all of that is very
subjective on the one hand. Those words are heard often
enough and repeatedly enough in psilocybin sessions and
after psilocybin sessions, along with this description
of the psilocybin experience as one of the
most profound of one's life, or one of the most positive in
the ideal case of one's life that they are worth exploring. We should also, of course,
explore the so-called bad trip, the possibility
that someone will have a not good time or even
very frightening time while under the influence
of psilocybin. So there have been
some scientific studies that have explored what sorts
of subjective experiences. That is thoughts, and feelings,
insights that people have, that relate to positive
therapeutic outcomes, and more generally
with the sense that the psilocybin journey
was positive or maybe even tremendously
positive in one's life. So while there's
a century or more of writings about
psychedelics that describe things like enhanced
feelings of connectedness, or dissolution of the ego,
the loss of one sense of self, and then the regaining of
one's sense of self, and so on. There's a particular
paper that describes some of those things in
terms of rating scales, that is the sorts of tests that
people can take in which they answer particular questions,
and that link back to things like feelings of connectedness
and ego dissolution, that allows us to put
some numbers to those m and to look at some of
the statistics associated with those experiences. And this is really
what's important about scientific
studies, whether or not a measure is subjective. So if someone's self-reporting,
how they felt or feel, or whether or not it's
measure of blood pressure, or of a chemical in the
bloodstream, et cetera. It's the use of
numbers and statistics that allows comparison
between different groups. And that can be
compared between studies that allows us to make some
firm conclusions about what sorts of things psilocybin
may or may not be doing when it's effective or not. So the paper I'd
like to highlight is entitled quality of
acute psychedelic experience predicts therapeutic efficacy
of psilocybin for treatment resistant depression. I'll put a link to this paper
in the show note captions. But the basic
contour of this paper is that they looked at
subjects that underwent two different psilocybin sessions. One, at a relatively
low ish dose of 10 milligrams of psilocybin. And that would be
equivalent to about 1 gram of psychedelic
mushrooms more or less. And a second session
involving subjects taking 25 milligrams
of psilocybin, or what's roughly
equivalent to somebody taking 2.5 grams of
psilocybin mushrooms. Those people then
answered what's called the altered states of
consciousness questionnaire, which allowed them to address. And here I'm
paraphrasing the quality of experiences in the 25
milligrams psilocybin session. So without going
into too much detail, it's often the case in
these two session studies that subjects will take
a slightly lower dose of psilocybin, to familiarize
themselves with the experience. And then the higher
dose that leads to the more intense experience. Intense meaning a bigger, more
intense peak, a longer session overall, greater
distortions in emotionality, and perceptual
experience, all the stuff we talked about before. So what this study found is
that one of the key features, if not, the key feature of
a positive quote-unquote psychedelic experience
is this sense of oceanic boundlessness
occurring at some point during the psychedelic journey. Now, oceanic boundlessness
doesn't necessarily mean anything to any of us. It probably means different
things to different people. Is this idea that one is
experiencing something extremely unusual, even mystical
beyond this world and one's normal experience. But that it's not aligned
with any specific outcome in the moment. It's not directly attached to
any one feeling, or memory, or thought process. It's a little bit
tough to describe because I can guarantee you. I'm not on psilocybin or
any psychedelics right now. And I can only imagine
that you're not. Although some of you might be. I can't even imagine
what this podcast would be like for somebody
on psilocybin at this moment. But in any case,
oceanic boundlessness, a feeling of the
experience being mystical, and not really heading in
any one particular direction. Just a feeling of massive
connectedness with one's environment both in
the room and session. Perhaps with the guides with
oneself, with one's past, with one's present,
people outside the room with the entire world,
maybe even the universe, that sort of thing. The intensity of that experience
of oceanic boundlessness, the mystical experience seems
to be positively correlated with positive
therapeutic outcomes. That is relief from
major depression. Now, during the
psychedelic journey, as we talked about
before, there are a number of steps that one
typically goes through. So there's the build up
to first experiencing the effects of the
drug about maybe 20 to 45 minutes into
the journey or trip. Then the peak. And it is during that
peak that people often feel the sense of
oceanic boundlessness. However, it's also
often the case that it is during the peak
or the maximum intensity of emotion. And we know based on
direct measurements also increases in blood
pressure and heart rate often very significant increases
in anxiety and fear as well, that people will experience
things like ego dissolution. And the guide's
role at that point is, of course, to
keep the person safe, make sure they don't run out of
the room, jump out of a window, run into traffic. Sadly, these are
things that have happened outside of a strong,
healthy, safe set and setting. But the guide's role is
to keep the person safe, but also to encourage
them to let go and move through that experience
to experience the anxiety, allow it to peak, allow
them to see that they're not going to die from that anxiety,
they're not going to dissolve. They won't lose their
sense of self completely, or they may temporarily
feel as if they lose their sense of self. But then they feel it
restored at various intervals during the peak or as
they exit that peak and move toward the say second,
third, fourth, fifth hour of the session. So when exactly these feelings
of oceanic boundlessness and ego dissolution occur? It varies from person to person. But typically, it's
during the peak that the ego dissolution,
the fear, and the need to quote-unquote let
go is most typical. I think perhaps the best
way to describe the data in this paper in a way that's
meaningful to everybody is to refer you
to figure 2, which if you're not
looking at the paper, won't mean anything to you. But I'll describe it. And if you do want to take
a look at figure 2 again, you can access the paper
in the show note captions. What they did is they
looked at a number of different subjective
measures, things like experience of
unity, the feeling that one is connected to
others and to the world. Things like spirituality,
whether or not the whole thing felt like
a spiritual experience, whether or not it was a
blissful state, whether or not there were insights, whether or
not somebody felt disembodied out of body, whether or not
somebody had a lot of anxiety, whether or not they had these
synesthesia, these blending of visual, auditory, touch,
and breathing, and things of that sort. And they addressed,
which of those measures related to the positive
clinical outcomes that were observed later after
the psilocybin wore off. And while I'm not
going to go point by point through each
one of these measures, there's a general feature to
emerge from the study, which is that the experience of unity,
the sense that the psilocybin journey was spiritual,
an experience of bliss at some point inside of
the psilocybin journey. The sense that
there were insights, that there were learnings about
one's life and one's self. When those things were
experienced very strongly, that correlated with
the person being what was called a responder
to the psilocybin treatment, meaning they got relief
from their depression. Whereas people who
felt less of that-- OK, so the non-responders
as they're called, the people who do
not benefit so much in the long run from
the psilocybin treatment tended to report less of
an experience of unity, less of a spiritual experience,
less of a blissful state, less insightfulness, and so on. Whereas there were very few
differences between the people that derived benefit from the
psilocybin treatment and those did not along the
dimensions of synesthesia, this blending of
different perceptions that ordinarily doesn't
occur for most people. Or complex imagery, right? Put simply everyone who took
psilocybin in this study at 25 milligrams saw a
complex imagery, they saw a lot of
hallucinations. But just seeing
hallucinations did not lead to the positive clinical
outcomes in terms of mood. Anxiety was a very
interesting measure here. Because ordinarily, we think
of the ego dissolution, the letting go is
such a key component of the psychedelic
journey in terms of the positive
therapeutic outcomes. This has been
discussed quite a lot. And in full disclosure,
Robin Carhart-Harris has already come on to record
an episode of The Huberman Lab podcast. That episode hasn't
been released yet, but it will be released soon. And he talks about
the importance of this letting go in terms of
the positive clinical outcomes of the psilocybin journey. And indeed that is true. And I should also mention
that Dr. Matthew Johnson from Johns Hopkins who also
runs a laboratory exploring psychedelics and their
role in treating things like eating disorders,
and depression, et cetera. Also, doing incredible work. Also talked about the
importance of letting go during the
psilocybin journey. This ego dissolution,
this ability to move through the anxiety. And, again, I can't
underscore this enough because it's been told
to me over and over again by the top researchers
in this area. That people head into that
peaking phase of the psilocybin journey, and oftentimes it
is not pleasant for them, they're feeling like it's
uncomfortable, it's scary, and their heart rate is up,
and their blood pressure is up, and they're having a
hard time calming down, and they want to calm down. But it does seem that while the
guides should not ramp them up and get them more
stressed, that the ability to move through that
stressful period to somewhat guide oneself or to
be encouraged to guide oneself through that peak. And that anxiety and the
fear of losing oneself and the so-called ego
dissolution that occurs is an important feature for an
effective therapeutic session. In this study, anxiety
itself was inversely correlated with a positive
therapeutic outcome. So this is important
and somewhat nuanced. On the one hand, I'm telling
you that the letting go, the ego dissolution
does seem to be important in terms of reporting
a psychedelic experience as effective as having
accomplished something. And perhaps even explaining
some of the long-term positive effects to emerge from
that psychedelic journey. In this case,
psilocybin journey. However, non-responders,
that is people who did psilocybin,
but did not have a positive therapeutic
outcome in comparison to the responders,
those non-responders tended to have higher
subjective ratings of anxiety than did the responders. So this is important. And what it speaks
to is the fact that while yes letting
go during the session, experiencing some anxiety,
perhaps even ego dissolution, and the dissolving of self,
and then the return of self is important. It is also important it seems
that anxiety not be so, so high or subjectively
experienced as so high. That one does not experience
the positive neuronal rewiring that leads to a more
pervasive elevated mood. So I'm definitely
saying two things at once because I'm trying to
capture the data accurately. It would not be fair for me to
say, just let go, experience as much anxiety as is possible. And that's part of the process. Yes. Letting go-- again,
in air quote seems to be important for
one's experience of the psychedelic journey, in
particular, around the peak. That occurs about
two hours in or so. However, extreme
levels of anxiety seem inversely correlated
or negatively correlated would be the better
way to put it with the positive
therapeutic outcome or relief from depression. So this takes us back
to all of the things we've been talking
about thus far. Not just the chemistry
and biological action of psilocybin, but
the key importance of getting dosage right, the
key importance of making sure that you're in a
safe environment, but also one in which the guides
really know what they're doing. I think this is one of the
biggest and most important reasons for having well-trained
guides who really understand the contour of the
psychedelic journey, but are also trained
in how to help somebody with their anxiety in
real-time while they're under the effects of psilocybin. And, of course, to help people
integrate those feelings of high anxiety and
maybe guide them back down to a calmer state
during the psychedelic session itself. And here I can just mention some
unpublished data and studies. And, again, these
are very preliminary. But through discussions with
Dr. Matthew Johnson who's running these psilocybin
and other sorts of psychedelic trials
at Johns Hopkins, he and I discussed
the importance of having a real-time tool
to adjust to anxiety while under the influence of
psychedelics like psilocybin. And there he asked, and
they've started to incorporate, as my understanding, some of
the real-time respiration tools that is breathing tools
that we know based on work in my laboratory, Dr.
David Spiegel's laboratory, can reduce anxiety very
quickly in real-time. And that involves the use of the
so-called physiological sigh. I've talked a lot about this
before on previous podcasts. So rather than explain
it to you again here now, we'll put a link to
the physiological sigh. I do a demonstration of it
in the show note captions. I'll also link to a recent
paper that we published in Cell Reports Medicine. This was a collaborative
work that my laboratory did with Dr. David
Spiegel's laboratory at Stanford School of Medicine. Showing that the
physiological size among the different deliberate
respiration techniques, one of the fastest and
most effective ways to reduce levels of
autonomic arousal a.k.a. anxiety or stress. And Dr. Matthew
Johnson's laboratory has started to incorporate
physiological size within these psychedelic
sessions as a tool that the guides can refer people
to before the session begins, teaching it to them. So they realize they
can calm themselves down if necessary in real-time. It works the first time,
it works every time. This is not because it's some
magic breathing technique that I created. It certainly is not. This is a naturally
occurring pattern of breathing that occurs
in sleep and in waking. But that when done
deliberately, leads a very rapid and
quite significant decreases in stress and anxiety. And then when people are inside
of the psychedelic session, if they feel their anxiety
levels are going too high, they're heading toward
what might be called a quote-unquote bad trip. They're starting
to panic or really think they're going to
have a panic attack or die. Again, the subjective
experience is going to be layered on top of
the physiological experience of one's heart rate
being really elevated, saw a stress and agitation. By using the
physiological sigh inside of the psychedelic session,
Dr. Johnson's laboratory. And I believe, at least
one other laboratory are starting to use
breathing techniques such as the physiological
sigh as a way for these people who are under
the influence of psilocybin to self-direct their own calm. And to bring that
level of anxiety down so that they can continue
to move through the peak and move through
the other phases of the psychedelic
journey in ways that could be most beneficial for them. So to close out the description
of this really wonderful study-- and by the way, it's another
one from the Carhart-Harris laboratory, about the subjective
experience of ego dissolution or oceanic boundlessness,
this mystical state as so key as a component of a
positive psilocybin journey. I'll just read for you the
final sentence of this paper because it captures it so well. Quote, it seems vital that
appropriate consideration is paid to the importance of
promoting a certain experience as the quality of
that experience may be the critical determinant
of therapeutic success. Now, before we
move into what will be a very brief
description of some of the other rewiring
phenomena, that psilocybin can induce, and then into some
of the therapeutic applications of psilocybin as they relate
to these recent really exciting clinical trials for depression,
and addictive disorders, and things of that sort. I just want to cue
everybody to a paper that I think many
people will want to take a look at in
thinking about psilocybin. And I'll provide a
link to this paper as well in the
show note captions. This paper is entitled
therapeutic use of psilocybin,
practical considerations for dosing and administration. And this is a wonderful
paper because it really goes step by step through the
pharmacology of psilocybin of which you now
understand a bit. But it goes into
a bit more detail. But then it also
really nicely describes the contour of a
psilocybin session and what's happening at
the level of chemistry early, middle, peak, and toward
the end of the psilocybin session. And then also
importantly, it gets into issues of dosage
and translating from mushrooms, to psilocybin
itself, to psilocybin, things I talked about earlier. But in a bit more detail, if
you'd like to see that detail. And then perhaps
most importantly, there's a section on
contraindications where it points out that
of course, women who are pregnant
or breastfeeding, people who have a
predisposition to psychosis, those people should
really avoid the use of psilocybin and other
psychedelics entirely. It also talks about where the
evidence is strong, moderate, and weak for the use of
psilocybin for treatment of various disorders. And I can just summarize
that very quickly because it's where we're going
to head in a few minutes, which is that the most evidence for
positive therapeutic outcomes in response to psilocybin taken
and conducted in the manner that we've been describing today
in terms of dosage, and journey set, and setting is for
cancer-related depression, cancer-related anxiety, and
treatment resistant depression. That's where most of
the evidence resides. There's also some evidence for
the use of psilocybin journeys. And, again, this is typically
one or two psilocybin journeys spaced in the cases of
two journeys anywhere from one to two weeks apart. And, again, with all
of the same contour of supports and set
and setting that we've been talking about today. And there there's some
evidence for improvement in terms of outcomes in alcohol
use disorder, and dependence, and tobacco addiction. And then finally, there's
the least amount of evidence. Although there is clinical
trial support for relief or partial relief for
obsessive compulsive disorder, cluster headaches and
migraines, and demoralization due to AIDS diagnosis. So this paper has a lot of
really interesting information in terms of different
conditions, in terms of dosage, and again,
contraindications, and what's called adverse events,
what sorts of bad things can and do happen as a
consequence of psilocybin and other types of
psychedelic journeys both during and after those
psilocybin or psychedelic sessions. And we'll talk a
bit more about this when we go into some of
those clinical studies. Because adverse
reactions is always a key measure in
any clinical study. So very soon, we'll get into
the more recent clinical studies related to psilocybin for the
use of treating depression and some other conditions. But before we do
that, I'd be remiss if I didn't talk about how
psilocybin does and does not change the brain, what is and
what is not known about that. In fact, when I put out the call
for questions about psilocybin, many of the questions
related to these issues. The first thing to understand
is that a psilocybin journey is really a way to try and put
that wedge under the boulder as I described it to try
and invoke neuroplasticity of a particular kind. And in that way,
it's remarkable, if you think about it, that
everyone has different lives different experiences. Psychedelics, in
this case, psilocybin are activating these brain
networks that each of us has more broadly than they
would normally be activated. These are very abnormal patterns
of thinking, and perceiving, and experiencing our emotional
and physical life, et cetera. And yet so often, the
outcomes are positive. Not always, but the
outcomes are positive. The experience is
positive, even though it might have these anxiety moments
or components within them. It's very important to
understand that psilocybin and the journey while important
are not really what all of this is about. It's really about
neuroplasticity. So researchers, in
particular, neuroscientists are very intensely
interested in understanding what sorts of neuroplasticity
psilocybin creates. Because it turns
out there are lots of different types or processes
involved with neuroplasticity. For instance, brain networks,
behavior, thinking, emotion, et cetera can change because of
the addition of new neurons. That's one form
of neuroplasticity that's referred to as
neurogenesis, the production of new neurons, most typically
in the so-called dentate gyrus or other subregions
of the hippocampus, a brain area involved
in learning and memory. Neurogenesis in other regions
of the adult human brain are exceedingly rare. And to be honest,
may not occur at all. This is a debated area. We could do an entire
episode about this. But for the most
part, neuroscientists don't really believe that
your neocortex, your striatum, your cerebellum has that
much neurogenesis that's related to learning and
memory of new things, or new experiences. And we don't actually think
that occurs as a consequence of taking psilocybin either. Now, some of you who
are familiar with, for instance, the cerebellum. You might be saying, wait,
what about granular cell proliferation in the cerebellum? Or what about the
rostral migratory stream from the subventricular zone
where there are neuroblasts spitting out little
new neurons that migrate in through the nose to
replenish the olfactory neuron population? Yes, that's all true. That does occur. It's been observed in mice,
it's been observed in monkeys. And to some extent, it's
been observed in humans. But, again, I repeat it is not
a prominent feature of learning and acquisition of
new skills, new ideas, or new emotional states. Perhaps the best
supported evidence for neurogenesis underlying
new thoughts, experiences, abilities, emotions, et
cetera is the production of new neurons in
that dentate gyrus subregion of the hippocampus. And that probably
does occur in humans. But neurogenesis is not
really the dominant mode of changing neural
circuitry in adult humans. It might be a player
in adolescence, in young childhood. It is certainly a player
before we are born when we are still in utero. But then the brain
is being wired up in many different
ways, including the addition of new neurons
and changing of connections. All of this is to say that
while neurogenesis is a really sticky idea and it
makes great headlines, the addition of new neurons
is not really the way that the brain changes under
psilocybin, other psychedelics, or just generally. It's perhaps responsible
for maybe 1% to 2%, and I'm being generous
there, of the rewiring events that are going to be most
important for all of us. So we need to set that
down and cement that there. Until further evidence
comes out to the contrary, that's certainly
where I and here I feel comfortable speaking for
the majority of neuroscientists out there, professional
neuroscientists. That is the paper showing adult
neurogenesis are interesting, but they don't
really explain most of the plasticity that occurs
in the adult human brain. So if neurogenesis
ain't it, what is? Well, it's very clear that
psilocybin, other psychedelics and any behavioral or
drug intervention that can induce neuroplasticity does
so largely through the addition or strengthening of
new neural connections or through the
elimination or weakening of other neural connections. And if you look at the data
exploring the mechanistic basis for psilocybin induced
neuroplasticity, it's mostly focused on animal
brains, animal models, mice and rats, in particular. A little bit on primates,
but mostly mice and rats because that's where
the interventions can be done of knock out animals, of
imaging the brain in real-time. Of course, there are
the beautiful studies of Robin Carhart-Harris
and others exploring neuroplasticity at the
level of brain imaging, at the level of
ultrasound measurements, of how active are certain brain
areas in humans, how extensive is the modularity
or not extensive is the modularity,
et cetera, the stuff we talked about earlier. So in other words, there
are neuroplasticity studies, the effects of
psilocybin in humans. But in terms of underlying
mechanisms of neuroplasticity, I think the predominant theory
is that psilocybin induces neuroplasticity through the
addition of novel connections in those pyramidal neurons
of the frontal cortex, elsewhere in the
cortex, and certainly also in the visual cortex. Probably also subcortical as
well below the cerebral cortex in areas like the thalamus,
maybe even in the brain stem as well. And that those
neuroplasticity events are structural and functional. And they involve a
couple of basic events. The most prominent of which
is the growth of dendrites. Dendrites are those little
branches or processes that come out of the neurons,
not just the pyramidal neurons, but other neurons as well. But since we're talking mainly
about pyramidal neurons today. Both the apical,
those ones that top. They're called the apical tufts. They're the ones that
reach laterally to connect with other neurons,
communicate with other neurons that we talked about before. As well as the
dendrites that come out of the base of those
pyramidal neurons. Those processes grow in
response to psilocybin, as well as the addition of what
are called dendritic spines. So the dendrites
are the branches. The spines are these little
protrusions that grow out. Actually, here, I don't know
if this is coincidence or not. Again, I always say I wasn't
consulted at the design phase. But these little
protrusions actually look like little mushrooms. They have a little stalk
and they have a little head, a little spine, head. And those little
spines-- so think of these as like little
tiny mushroom appearing. OK. They aren't actual mushrooms. OK. The first person that puts in
the comments, oh, my goodness. I learned today that mushrooms
grow out of our neurons. When we take magic mushrooms,
that is not what I'm saying. What I'm saying is that
these little mushroom shaped protrusions that we're
calling dendritic spines do in fact grow out of
dendritic branches of neurons when animals ingest
psilocybin or are injected with psilocybin. And that those little
mushroom shaped protrusions are the sites of new excitatory
connections, new locations for input from other
neurons to activate those neurons that have
those little mushroom-shaped protrusions. If you'd like to see examples
of this, both movies and still shots, it's pretty remarkable. There's a paper that I'll
provide a link to in the show note captions. This was published in the
Journal Neuron, Cell Press Journal, Excellent Journal,
entitled Psilocybin Induces Rapid and Persistent
Growth of Dendritic Spines in the frontal Cortex In Vivo. So these measurements were
done in the mouse equivalent more or less of the
prefrontal cortex. There are some interesting
details in this paper, for instance, that those
new connections persist. So they don't just grow out
during the psilocybin being active in the bloodstream
and brain of the animal, they persist. OK. So this may again. May explain some of
the persistent changes that occur in people
after psilocybin journeys. They may too grow new spines. I should also mention
that a reduction in the number of dendritic
spines, these little mushroom shaped protrusions
in the frontal cortex neurons of humans occurs
in depressed patients. We know that from
postmortem tissue. And that drugs that
relieve depression or that treatments including
behavioral treatments, that provide some relief
from depression do seem to be correlated
with increases in spine growth in frontal
cortex neurons as well. So this raises a very
interesting idea, which is perhaps it's the
growth of new connections, these new dendritic spines
in particular neurons. That's created by
administration of psilocybin. That explains the
relief from depression that people experience. So this is just one paper. But it's one paper of a growing
body of work showing that, yes, indeed, psilocybin induces
both structural and functional plasticity in the
human and animal brain. It does that in the human
brain at therapeutic doses of anywhere from 10
to 25, perhaps even 30 milligrams per session,
one or two sessions. I should mention that the
mouse studies tended to use quite high doses of psilocybin. I wasn't shocked, but I was
somewhat wide eyed for a moment to realize that most of the
studies looking at changes in plasticity in the mouse
brain in response to psilocybin use the equivalent of 1
milligrams per kilogram of body weight, which
is if you do the math, and you translate what we were
talking about before in terms of dosages, I'll just
spare you all the time, it's about double, the sorts
of dosages that are typically used in humans. Maybe even triple in some cases. Now, it's often the
case in animal studies because of the
metabolism of animals being different, but also
because seeing effects of drugs in animal studies
can be difficult. They did use a dose response
anywhere from 0 to 0.25 to 0.5 to 1 to 2
milligrams per kilogram of psilocybin in the study. So they had a dose
response curve. But focused mainly on this 1
milligrams per kilogram dosage. In any event, the
point is that many of the studies that
describe these pretty dramatic structural changes
in the animal brain, most typically the
mouse brain in response to psilocybin use
dosages of psilocybin that if translated
to humans would be about double the
human therapeutic dose. So that is something
that we need to take into consideration. Nonetheless, it's very clear
that in both animal studies and humans,
psilocybin is inducing both structural and functional
changes in brain circuitry. And that in humans, the
network connectivity is being changed dramatically. We talked about
those data earlier. And that the underlying
basis for that might be, again, might be. We don't know for sure. The addition of new dendritic
spines on these pyramidal neurons that we've been
talking about repeatedly throughout today's episode. Although neurogenesis
perhaps and other modes of neuroplasticity,
such as the elimination of certain connections. Perhaps related to unhealthy
maladaptive thoughts, or feeling that a particular
sad song is overwhelmingly sad. It could be the case that
those sorts of things change subjectively
because of the removal of neural connections. If you're going to think like
a neurobiologist or scientist for that matter,
you don't ever want to think that one
mechanism can explain all the effects of a given
drug or a given experience. It's almost certainly
likely to be the consequence of multiple
mechanisms acting in parallel. And because I know there
are people out there who would like to even more about
the neuroplasticity induced by psychedelics,
including psilocybin, there's a wonderful review
that I provide a link to in the show note captions
entitled, Psychedelics and Neuroplasticity: A
Systematic Review Unraveling the Biological Underpinnings
of Psychedelics. This review is great
because it goes a step beyond just psilocybin
and psilocin binding to the serotonin to a
receptor, and things like brain derived neurotrophic factor. It actually talks a lot about
the intracellular signaling and exactly how neurons change
their excitability patterns based on this activation of
the serotonin 2A receptor. It's probably more
detail than most of you out there are interested in. But if you are interested
in that level of detail, this is a wonderful
open access review. So a few minutes ago,
I talked about where there is strong, modest,
and somewhat weak or rather, I should
say, minimal evidence for the therapeutic
use of psilocybin to treat various disorders. And across the board,
it really appears that major depression
and so-called intractable depression, in some
cases, is where we're seeing the most
exciting research to date. Now keep in mind that because
of the Controlled Substances Act being invoked in 1970
in the United States, and because it was only
just a few years ago really, only about five years ago,
that psychedelics including psilocybin received what's
called a breakthrough status at the FDA. That there are now a
lot of clinical trials exploring how
psilocybin can impact various things like mood
disorders, addictive disorders, and so on. Prior to 2018, when that
therapeutic breakthrough potential was established
in the United States, I think a lot of people in
the so-called psychedelics community had the sense,
and really the belief that these drugs had
enormous potential. But they just weren't being
explored that extensively. So I do want to give a nod
to the incredible researchers such as Robin Carhart-Harris,
but also Matthew Johnson, Roland Griffiths,
Nolan Williams, and many others. OK. I'm certainly not
listing off everybody. That would take hours. But those researchers
have really pioneered both the legal efforts,
and the funding efforts, and most importantly,
the research efforts defining
the clinical data that I'm about to describe. And here, I'm going to
summarize the clinical data in a bit of a top
contour fashion just giving you the
kind of highlights. We will, of course,
provide links to the papers if you'd like to
look into it further. But I'm only giving
you the top contour because I've had the great
fortune of having Matthew Johnson on this podcast before. You can find that episode
at hubermanlab.com. Just simply put Matt's name or
psychedelics into the search function. It'll take you to that
episode in all formats or links to all formats rather. I've also had the great fortune
of sitting down recently with Dr. Robin Carhart-Harris
to talk about his work at University of California San
Francisco on psilocybin, LSD, Ayahuasca, and DMT as
it relates to depression and other disorders. And that episode,
which also will be released at hubermanlab.com
and on all platforms YouTube, Apple, Spotify. Really goes in depth into
these clinical studies and what those studies really
look like, who's in the room, whether or not
people just get one dose or two doses, how far
apart those are separated. All of that is covered
in extensive detail in that what I found to be
wonderful discussion with Dr. Robin Carhart-Harris. So if you're interested
in all of the details as it relates to clinical
application of psychedelics, stay tuned for
that episode soon. Again, you can find
that at hubermanlab.com and on all platforms. In the meantime,
I would be remiss if I didn't include
a bit of discussion about what has been observed
in terms of using psilocybin journeys as a way to treat
depression because the data are just oh, so exciting. Again, these data really
started to surface as the consequence
of studies that were initiated around 2006 in
just a few select laboratories. And then really
picked up in terms of the number of
laboratories and number of studies between 2018 and now. So what you'll
notice is that most of the papers I'm about to
describe were published in, for instance,
Phenomenal Journals, New England Journal
of Medicine in 2021, and New England Journal of
Medicine November 2022, Journal of the American Medical
Association Psychiatry just very recently, 2021. So these are very recent papers. Essentially, all of
these clinical studies involve either one or
two psilocybin sessions. The dosages that were explored
range from 0 milligrams. So placebo, if you will. 10 milligrams, in some
cases, 25 milligrams, in some cases, 30 milligrams. And most typically, people
received the same dosage for both sessions if indeed
they did both sessions. However, there's
at least one study looking at just
one single episode of psilocybin administration. So this is the paper entitled. No surprise single dose
psilocybin for treatment resistant episode
of major depression. This was published in the New
England Journal of Medicine in November of 2022. I'll just summarize the results
of this single application study. They randomly assigned
subjects who had treatment resistant depression. So they had resisted
treatment to other things. To receive a single dose
of a synthetic formulation of psilocybin. So they're not eating
mushrooms, they're getting a synthetic
dose of psilocybin. But the dose is known of either
25 milligrams, 10 milligrams, or 1 milligram, which
was the control. And they receive
psychological support. There were a number of different
tests, subjective tests of depression taken before and
after the psilocybin journey. They had about 75 to 79
participants in each group. Again, at the three different
doses 25, 10, or 1 milligrams. And they looked at the
changes in these scores, these depression related
scores on these tests. There are many results from
this paper one could summarize. But among the most
important results I can summarize
from the discussion and here I'm paraphrasing, that
the change in baseline levels of depression that is at week
three following the psilocybin session was
significantly better. That is people experienced
more relief or more people experienced more relief
from the 25 milligram dose than from the 1 milligram dose. And this is important. There was no
significant difference between the 10 milligram dose
and the 1 milligram dose. This really points to the
fact that the 25 to 30 milligram dose that's used in
the largest numbers of studies exploring treatment resistant
depression really seems to be, I don't want to say the best
dose, but the most effective dose at least in this
clinical context, in this set and setting and
with this particular patient population. So we want to be careful to say
that so that one doesn't just translate that 25 milligrams
is better than 10 milligrams. Although in this study it
was for sake of treatment resistant depression relief. There were a number of other
key aspects of this paper. In particular, the exploration
of so-called adverse events. So things like
headaches, propensity for self-harm, actual
self-harm, anxiety, and so on. It's worth mentioning that
there were adverse events in essentially every group. The number of adverse
events was highest in the 25-milligram dose group. This is observed in
other studies as well. With higher dosages,
there tends to be greater relief from
depressive symptoms, but also a greater chance
for adverse events. Some of those adverse
events can be quite severe. So feelings of suicidal
ideation, et cetera. Some of them one could
consider a little less severe, mild headache, or severe
headache that was transient, or anxiety that was transient. Again, highly
individual responses. We could go line
by line and table by table through this paper,
which we won't because there's a lot of data. Again, we'll provide
a link to this paper if you'd like to
peruse it yourself. It's fairly
straightforward to read. That's one thing that's nice
about these clinical trials is they tend to be written in
fairly non-technical language. Although there's a little
bit of technical language. The important point
is that a single dose of 25 milligrams of psilocybin
provided significant relief from treatment
resistant depression in this particular
patient population. But it is not the case
that 100% of the people who took 25 milligrams of psilocybin
experienced that relief. However, the
majority of them did. Now, when you say
majority in science, you really need to
look to numbers. And the reason I'm not telling
you, oh, it was 75% or 60% or 50% is because it
depends on which time point people were analyzed. People were asked about their
level of depression relief immediately after
one week after, two weeks after, or
three weeks after. And the degree of relief
tended to change over time. In fact, it tended to
diminish over time. But it was also stable
or remarkably stable, I should say, at
least by my read in the 25-milligram dose group. And that is summarized nicely
in figure 2 of the paper. Because they explored these
people's levels of depression out to week 12. And they still saw
a significant degree of depression relief 12 weeks
after the single 25-milligram psilocybin dose session. So as I mentioned earlier,
there are now about a dozen or so excellent
studies, clinical trials exploring the use of single
or two session psilocybin treatment in that 25 to
30-milligram range, which seems to be the most effective
dose for long-lasting relief from depression. Each one of those studies
explored something different as is important. Replication is also
important, of course, in order to validate
previous studies. But, for instance,
there have been comparisons of psilocybin versus
SSRIs or other antidepressants. There have been comparisons of
psilocybin plus psychoanalysis or cognitive behavioral
therapy, versus cognitive behavioral therapy
alone, or psychoanalysis alone. And so there's a
lot of evaluation now of the clinical outcomes. And the statistical outcomes
of these subjective measures and even some objective measures
of neurochemistry where that's possible in terms of
trying to understand if and how psilocybin is
effective for the treatment of depression. And the major takeaway
is that, indeed, it does seem to be the case. And the numbers that I feel
comfortable not throwing out there, but putting out to
you reflect my conversation with Robin Carhart-Harris. Again, that will
be released soon at hubermanlab.com,
as well as takeaways from what I would say are the
six broadest studies, meaning they have the widest range
of age groups, the broadest demographic in terms of the
subjects, their backgrounds, their levels of education, men,
women, ethnicity, et cetera. And a lot of that
can be summarized in the paper entitled, Effects
of Psilocybin Assisted Therapy on Major Depressive Disorder. This was a particular
randomized clinical trial. But in the discussion, I
think they summarize it quite well, which is that if
you look at the number of people who take this 25-milligram dose
twice in sessions spaced about a week apart, what you will
find is that anywhere from 60% to 75% of the people who have
major depressive disorder who do these psilocybin sessions
in the proper setting, report a good
experience with it, have minimal adverse events
coming out of those sessions and in the weeks following,
those people experience substantial positive relief
from major depression. In ways that other treatments
that they had explored, including antidepressant drugs,
cognitive behavioral therapy, and other types of therapy
alone could not provide. Now, it's a general feature of
these clinical trials focusing on psilocybin that
people are asked to stop taking their
antidepressants prior to participating
in the trial. It's also a general
feature of these trials that people are encouraged
to not suddenly start their antidepressant treatment
immediately afterwards because, of course, that could confound
the results of the psilocybin treatment. However, and this is a very
important thing to note all subjects were
encouraged not to avoid taking those
antidepressant medications if, in fact, their
clinician felt that it was important for
their immediate and long-term survival. So no one should be
reckless in thinking about what to add or delete
from their drug protocol when dealing with depression. All right. The outcomes could be
very severe in that case. Nonetheless, we can
paraphrase from the discussion of the paper I just mentioned. Because it really highlights
the incredible results that psilocybin applied in these
particular therapeutic settings are providing. And here, again,
I'm paraphrasing. The present trial
showed that psilocybin administered in the
context of supportive psychotherapy consisting
of approximately 11 hours of psychotherapy. So this is going
to be two sessions of the psilocybin with
proper therapeutic support. Produced large rapid and
sustained antidepressant effects. The effect size is
reported in this study were approximately 2.5 times
greater than the effects sizes found in psychotherapy. And more than four times
greater than the effect sizes found in psychopharmacologic
depression treatment studies. In other words, four
times the positive effect observed with typical
SSRIs or other pharmacology of that sort. These findings are consistent
with the literature that showed that combined
pharmacotherapy and psychotherapy were more
efficacious in the treatment of major depressive disorder
than either intervention alone. So, again, this
points to the fact that combining drug
therapy with talk therapy as it's often called
is going to be more effective than
either treatment alone. Here are the drug therapy
is psilocybin therapy. And, again, please don't take
the fact that in these studies, they tended to ask people to
not take their antidepressant medication heading into
the study as a sign that one should stop
taking their antidepressant medication. Rather I think this study and
other studies like it, again, which we'll provide
links to in the show note captions that are discussed
extensively in the episode with Dr. Carhart-Harris
soon to come, really point to
the incredible role that psilocybin can have
in creating an experience inside of the
session the journey or the trip as it's called,
as well as initiating neuroplastic events, perhaps the
addition of dendritic spines. Maybe even some
new neurons maybe. Although I don't think
that's the predominant mode. But that leads to these more
extensive connectivities in the brain, the so-called
reduction in modular networks enhanced activity in brain
areas that normally wouldn't be talking to one another. But not doing that in any
kind of haphazard way. It really does seem that the one
or two sessions of psilocybin that induce these feelings
of ego dissolution, that induce these feelings of
oceanic boundlessness, right? So mystical. And in many ways, it's
what I find so incredible about psilocybin and
other psychedelics is that despite the highly mystical,
highly subjective, and still at this time somewhat top
contour understanding of how they might exert their effects. You can highlight boldface
and underline might there because it hasn't really
been firmly established what the exact cell biological
rewiring events are. But there is now
what I would refer to as a center of mass of
data that point to the fact that psilocybin when taken
in the appropriate set and setting, at the
appropriate dosages can invoke the sorts of
neuroplasticity and changes in emotionality, in
perceptual experience, not just during the
psychedelic session, but for long periods of time
after the psychedelic session. That can provide really
remarkable relief from things like
major depression and perhaps other
psychiatric issues as well. And, of course, I
realize that many of you are listening to and/or
watching this episode. And you're not
necessarily depressed or thinking about
psychedelics like psilocybin in the context of depression. I hope today's
discussion allowed you to better understand how
psychedelics and psilocybin, in particular, because that's
what we've been talking about, are able to exert these
incredible effects that they seem to exert. This is not a call for everyone
to run out and do psilocybin. It is absolutely not that. It is, however, my attempt
to really put a magnifying lens on this incredible
area of research that's happening not just in
the context of clinical trials, but in the context of trying
to understand how serotonin and how drugs like
psilocybin, which in many ways mimic serotonin, and
more particularly, the activation of particular
receptors in the brain like the serotonin
to a receptor. I mean, just sit back
and think about that the selective activation of this
receptor, which is, by the way, associated with the expansion of
the neocortex across evolution. Didn't mention that
before, but indeed it is. How that can lead to
enhanced ways of thinking, changed ways of
thinking, actual learning inside of this short
4-hour or 6-hour session that we call the
Psilocybin Journey. So as is often the case,
perhaps as is always the case here on the
Huberman Lab podcast, we did a deep dive
into a topic today into the topic of psilocybin. What it is, how it
works, the different ways in which it changes
brain circuitry, how it creates the
experiences that we think of as the psilocybin journey,
what the safety issues are, what the so-called set
and setting are that can lend themselves to
positive therapeutic outcomes. And in doing so,
my goal was really to highlight several things. First of all, I am very
excited about the potential for psychedelics such as
psilocybin to provide relief for mental health issues
that to date have been very hard for people to access. In addition to that,
I'm just fundamentally interested in the brain and how
it works and how it can change. This thing we call
neuroplasticity. To me, neuroplasticity
is the Holy Grail of the human nervous system. As far as we know,
we are the animal that can have long-lasting
neuroplasticity throughout the lifespan. And if it requires
the use of compounds in a safe and controlled
way, such as psilocybin in order to achieve maximal
plasticity in a short amount of time, that's exciting. But, of course, that also
needs to be considered with all of the safety
precautions in mind that we talked about earlier,
including the fact that people who have a predisposition or
who have psychosis, or bipolar disorder, or a relative that has
psychosis, or bipolar disorder. Younger people, meaning people
25 years of age and younger. And really anyone
who's not working with a dedicated and
highly trained physician needs to be very cautious
about these compounds as well. They're very exciting. I think psilocybin is
an exciting and super interesting compound for
basic and clinical reasons and for other reasons as well. But they are sharp
blades as we say. And with sharp blades, you
can do incredible things, but you can also cut
yourself very badly. So all those considerations
need to be taken to mind. So I consider the science
and use of psilocybin to be an exciting, but
still preliminary area that I certainly am paying
a lot of attention to. And I know there's a
lot of excitement about. So stay tuned for the episode
with Dr. Robin Carhart-Harris. And we will probably
revisit psilocybin and we will certainly revisit
the other psychedelics and non-classical psychedelics
including LSD, DPT, 5-MeO-DMT, ketamine, MDMA, mescaline,
and all the rest in future episodes as well. If you're learning from
and/or enjoying this podcast, please subscribe to
our YouTube channel. That's the best zero
cost way to support us. In addition, please
subscribe to the podcast on both Apple and Spotify. And on both Apple
and Spotify, you can also leave us up
to a five-star review. If you have questions
for me, or comments about this, or any
other podcasts, or talk picks that
you'd like me to cover, or guess you would like me to
interview on the Huberman Lab podcast, please put those in
the comment section on YouTube. I do read all the comments. In addition, please
check out the sponsors mentioned at the beginning and
throughout today's episode. That's the best way to
support this podcast. Not so much during
today's episode, but on many previous episodes
of the Huberman Lab podcast, we talk about supplements. While supplements aren't
necessary for everybody, many people do derive
tremendous benefit from them for things like enhancing
the quality and the duration of their sleep, for things
like improving focus and for hormone
augmentation and much more. The Huberman Lab podcast
is proud to have partnered with momentous supplements. If you'd like to learn more
about the supplements discussed on the Huberman Lab podcast,
you can go to live momentous spelled O-U-S. So
livemomentous.com/huberman. If you haven't already
subscribed to our Huberman Lab podcast Neural
Network newsletter, the Neural Network newsletter
is a completely zero cost newsletter. That includes summaries of
podcast episodes and summaries of protocols, things like a tool
kit for improving your sleep, a tool kit for improving focus,
toolkit for neuroplasticity, toolkit related to deliberate
cold or deliberate heat exposure to fitness
to flexibility. And much more. Again, all zero cost. Simply go to hubermanlab.com. Go to the menu, scroll
down to newsletter, and provide your email. We do not share your
email with anybody. And, again, the newsletter
is completely zero cost. And to see previous newsletters,
you can simply scroll down a bit further on that
Neural Network newsletter page at hubermanlab.com, and
you'll find downloadable PDFs. And you can just click
on any of those PDFs. No sign up required. And if you're not already
following me on social media, it's hubermanlab on
Instagram, Twitter, Facebook, and LinkedIn. And on all those
places, I discuss science and science-related
tools, some of which overlaps with the content
of the Huberman Lab podcast, but much of which is distinct
from the content covered here on the Huberman Lab podcast. So, again, it's hubermanlab on
Instagram, Facebook, Twitter and LinkedIn. Thank you once again for joining
me for today's discussion all about psilocybin. And last but
certainly not least, thank you for your
interest in science. [MUSIC PLAYING]
