Welcome to Huberman Lab Essentials,
where we revisit past episodes for the
most potent and actionable science-based
tools for mental health, physical
health, and performance.
I'm Andrew Huberman and I'm a professor
of neurobiology and opthalmology at
Stanford School of Medicine. And now for
my discussion with Dr. Nolan Williams.
Thanks for joining today. I'm really
excited to have this conversation. I
have a lot of questions about different
compounds, psychedelics in particular.
>> Yeah.
>> But before we get into that discussion,
I want to ask you about depression,
broadly speaking.
>> Sure.
>> I heard you say in a wonderful talk that
you gave that depression perhaps the
most debilitating condition worldwide.
Yet in contrast to other medical
conditions like cancer, we actually have
a fairly limited number of tools to
approach depression. And yet the number
of tools and the potency of those tools
is growing.
>> Depression is u the most disabling
condition worldwide. Um what's
interesting about depression is it's
both a risk factor um for other
illnesses and it makes other medical and
psychiatric illnesses worse. Right? So
recently the American Heart Association
added depression as the fourth uh major
risk factor for coronary artery disease.
Right? So alongside the the risk factors
that we know hypertension, high blood
pressure, hyper lipidmia, high
cholesterol and diabetes, you know, high
blood sugar, those three have been on
the list for a long time and depression
end up, you know, being added to the
list as the fourth one. A lot of what
we're doing in the lab actually is um is
measuring kind of brain heart
connections and we can actually with
transcranial magnetic stimulation a form
of brain stimulation we can actually
decelerate the heart rate we can capture
that heart rate deceleration um over the
mood regulatory regions and so actually
a direct probe of that connection. We've
been very interested in a very
particular um clinical set of problems
around the the most severe and the most
high acuity settings that folks with
depression end up being in and that's in
you know emergency settings where they
go into inpatient units. the field
really hasn't developed a way of um you
know consistently being able to treat
that problem and folks end up getting
the same standard oral anti-depressants
that they've been getting outpatient and
and I came to this because I've you know
dual trained as a neurologist and
psychiatrist went back and forth between
neurology and psychiatry saw that in
neurology we have all of these ways of
treating acute brainbased problems and
really wanted to emulate that in
psychiatry and find ways to develop and
engineer new, you know, brainbased
solutions.
>> Many people out there probably think of
the relationship between the the heart
and the mind as kind of woo or kind of a
a soft biology. But here you're talking
about an actual physical connection.
>> Y what area of the brain is it?
>> You know, the first place where the
stimulation goes is called the
dorsalateral prefrontal cortex. It's
kind of the sense of control kind of
governor of the brain. And then it'll
and then what we know is that when you
use a magnet kind of what we call
Faraday's law this idea of um using a
magnetic pulse to induce uh an
electrical current in electrically
conducting substances. So in this case
brain tissue but not skull or sk sc
scalp or any of that or hair you avoid
all that just the brain tissue. Then you
have a direct depolarization of cortical
neurons, you know, the surface of the
brain's neurons in this dorsal
prefrontal. And if you do that in the
actual scanner, which we can do, you can
see that that distributes down into the
anterior singulate in the insula and the
amydala and ultimately the tract goes
into something called the nucleus tract
of solitarius and ultimately into the
vagus nerve into the heart. So the the
heart uh very consistently seems to be
the end organ of the uh dorsal
prefrontal cortex and if you do that
over visual cortex you don't get that or
motor cortex you don't get any of those
findings it's really specific to this
kind of control region of the brain and
so yeah it seems to you know it's our
work other other folks work Martin ARS
in um in in Europe uh the Netherlands
work showing the same connections I
think it's been replicated like four or
five times where I think TMS is really
interesting. Actually, we had a lot of
patients who've told me like my my
therapist told me that I wasn't trying
hard enough in therapy. These are, you
know, moderate to pretty severe
depressed patients. And as soon as we
get them well with with the TMS
approaches, you know, kind of rapid, you
know, 5day approach, and the next week
we come in and see them and they'll say,
you know what I did all weekend is I
looked at my therapy books and now I can
understand it. And so, you know, I
actually see TMS as a way of having kind
of exogenous sorts of cognitive
functions that in milder forms of
depression, we can pull off with
psychotherapy. You know, this idea of
being able to kind of turn that
prefrontal cortex on and have it govern
these deeper regions. In depression, the
deeper regions govern the prefrontal
cortex. In one case, it's like the coach
telling the player what to do and in the
other case it's like a player telling
the coach what to do and you you restore
order to the game.
>> You restore order to the game and what
it looks like is depression is a bunch
of kind of spontaneous content that's
semi valitional that's being kind of
generated out of this conflict um
detection system. the singulate. In
depression, it looks like the left
dorsal lateral does not sufficiently
clamp down on it. And what therapy
appears to do is to kind of restore
that. What we see with TMS over that
region is that we just exogenously do
the same sort of thing. We restore the
governance of the left dorsal lateral
over the singulate area and that is
correlated with treatment improvement.
So the degree in which you can re- time
or reeregulate in time the left dorsal
lateral over the singulate, the more of
an anti-depressant effect you have. TMS
is almost like exercise for the brain,
right? You're kind of exercising this
region over and over again with a
physiologically relevant signal and kind
of turning that system on. And what's
interesting for this show is, you know,
we had a couple of folks um you know,
probably five or six folks that have
actually told me this where if they
remit early enough in the week, we have
this very dense stimulation approach
where we can stimulate people really
rapidly over a 5day block. By Wednesday,
they're like totally zero down on the
depression scales, you know, even better
than most people walking around, like
really no anxiety, no no depression or
anything. By Thursday, the first guy
that that told me this, he came in and
he said, "You know, I was driving back
to my hotel and I decided to go to the
beach and I just sat there and I was
totally present in the present moment
for an hour." And he's like, "I read
about this in my mindfulness books, but
I experienced it last night and I've
never experienced anything like this
before." And I was like, "hm, that's
interesting, but kind of wasn't sure."
And then and then I didn't tell any, you
know, obviously any more patients about
that. And then about five over the last
couple of years when they get they were
mid early in the week by the end of the
week they're like going to the beach and
they're like totally having a what
people describe as a pretty mindful
present moment sort of experience which
is really interesting you know what that
is. I mean, I don't have full-on
scientific data to tell you, but it it's
just it's a it's an interesting
anecdote, right, that that folks when
you push them through this point of of
feeling kind of clinically well that
some people end up reporting this
additional set of features. So,
>> I want to make sure that before we dive
into ketamine and psilocybin that we do
touch on SSRI, selective serotonin
reuptake inhibitors, because we can't
really have a discussion about
depression without talking about SSRIs.
My understanding is that the SSRIs are
powerfully effective for certain forms
of obsessive obsessivempulsive disorder
and may also be effective for treatment
of depression. Is that right? And how
should we think about SSRIs? Are they
useful? Are they not useful? SSRIs
clearly work. Um, you know, many many
metaanalyses kind of proving that out,
right? That that in a subopul of
individuals, they achieve great benefit
for depression, for obsessivempulsive
disorder, for generalized anxiety
disorder, panic, you know, all these
things, you can see an improvement in
those symptoms um with what we call
SSRIs or selective serotonin reuptake
inhibitors. The issue is that they don't
work immediately, right? So they don't
work like the same day you start taking
them. And that that suggests that
probably it's not exactly the serotonin
being in there that's directly driving
it. That it's much more likely that it
may have some brain plasticity effects,
right? There's not a deficit of
serotonin. You're not born with uh what
people call a chemical imbalance. And
psychiatry has known this. This is not
actually new information anybody, you
know, it's kind of a rehashing of a
bunch of information we've known for a
while now. But in the lay press, it's
kind of hit in a way that it didn't seem
to to grab attention um before with
previous publications. But this idea
that this chemical imbalance idea is
wrong. I really think that part's
important because I think that what I'll
call psychiatry 1.0, right? this kind of
idea of Freud and and psychotherapy and
its and its origins. Um, it was a lot
around, you know, the your family and
those experiences and psychotherapy kind
of going in and correcting or helping
you to figure out or, you know, show you
being able to see or people hear you so
that you can eventually come to the
conclusion of certain cognitions that
aren't helping you, right? Things like
the schizophrenogenic mother and all of
that, you know, that was a concept at
some point, right? And so we've
transitioned from that to to the you
know for a long time the chemical
imbalance which I'll call psychiatry
2.0. You know this idea that there's
something chemically missing. The
trouble there for a patient right is
that it's telling it's sending a message
of there's something missing with me.
Whether it be my experiences I had no
control of over when I was a child or um
a chemical in my brain. What I think's
really powerful with with TMS,
um, you know, really powerful with TMS
and a level even powerful with the
psychedelic story is it's saying
something different. You know, TMS works
and there's no serotonin coming in or
out of the brain, right? And we're doing
a rapid form of TMS that works in 1 to 5
days. So, there's no there's it's very
unlikely that there's some long-term
kind of upregulation of serotonin that's
driving that. So our work actually kind
of pushes back on this serotonin
hypothesis as being kind of the center
of depression because it says look we're
not giving anybody any serotonin. We're
simply turning these brain regions on
and we're focused on the circuitry and
that's psychiatry 3.0. It's not just
like neurom modulation. Neurom
modulation is a really nice you know use
case for psychiatry 3.0 because it's a a
way to focally and directly perturb
brain regions in in whatever modality
you're using. But you know there are a
lot of a lot of groups that are actually
doing neuroiming before and after and
they're able to see circuit level
changes for something like psilocybin or
ketamine long after the drug is gone.
Right? Suggesting in those same brain
regions converge. So the subgenial
default mode network connection that we
see is changing with our our our stand
um Stanford neurom modulation therapy
technique. It's that same set of brain
regions that that ketamine and uh
psilocybin seem to act on act on these
connections between brain networks that
seem to shift. And so it refocuses the
story on something that's highly
correctable and it's it's basically
electrphysiology
and it's basically kind of recalibrating
a circuit that is re-calibratable
instead of I have something missing or I
have some set of experiences early in
life that are um that are going to
forever trap me in these these
psychiatric diagnoses. And so it kind of
challenges that idea. And I think that's
what's so powerful about psychiatry 3.0.
Um this idea of focusing on the circuit
because it gets us gets us into thinking
about psychiatry and psychiatric
illnesses is something that are
recoverable. People can get better.
People, you know, we've seen with our
TMS techniques, we've seen it with with
some of the psychedelic work that we've
done where people are actually in normal
levels of mood for sustained periods of
time or
>> within 5 days
>> within five or less days. And in the
case of of the psychedelics within a few
days, right? So we can get people out of
these states, they're totally well.
There's no drug in their system at that
point. In the case of the psychedelics,
it was never a drug in their system in
the case of of TMS. And it and it just
tells us that that it's it's it's
fixable. It's just like an arrhythmia in
the heart. It's like a broken leg. We
can go in and do something and we can
get somebody better. Then I think what's
what's empowering and what a lot of
patients have told me is they say you
know I've gotten dep you know some
people will relapse and need more
stimulation or need more psychedelics or
whatever it is but they'll tell me I
don't fear that I'm chronically broken.
I don't fear that the chemical imbalance
is still imbalanced. I don't fear that
these things that I couldn't control in
my childhood, you know, are going to be
there and drive this problem forever.
And I think that's that's what's so
powerful about this.
>> And that brings me to this uh question
about psychedelics and and the frankly
the altered thinking and perception that
occurs in in highdose psilocybin
clinical uh sessions. Many people do
report improvements in uh trauma related
symptomology and depression as I
understand it from my read of the
clinical trials after taking psilocybin
because during those sessions something
comes to mind spontaneously. They will
report, for instance, a new way of
seeing the old problem. That's right.
>> And the old problem could be the voice
that they're no good. They'll never
nothing will ever work out or could be
even more subtle than that. Why do you
think the brain would ever hold on to
rules that um uh don't serve us well?
>> I think it's an it's an it's an evol
evolutionary neurobiology answer, right?
I think that we end up being a result of
of probably a lot of biology that's not
that useful in the modern era. And I
think in the brain for for say let's say
PTSD, right? A lot of a lot of veterans
come back and they experience these PTSD
symptoms and they're not at all useful
back home, right? They hear some loud
noise and all of a sudden they're behind
a car or they're behind a you know I've
heard of folks you jump and run behind a
trash can or whatever in the middle of
San Francisco when they hear a loud
noise. But if you put them back in the
battlefield,
>> highly adaptive.
>> That's highly adaptive, right? We hold
on to those things from I think an
evolutionary neurobiology standpoint.
But what seems to for whatever reason
kind of alleviate that are these um are
these substances some new like MDMA,
some that have been around for thousands
of years like psilocybin seem to have a
therapeutic effect that seems to be
pretty longlasting for these phenomenon.
And so it's it's just curious, right?
It's curious that in the absence of that
these things will keep going on and on
but in the presence of that exposure
then all of a sudden you see a
resolution of the problem and we have
some work now we're treating folks with
Navy Seals the anecdotes that we're
getting right are folks are coming back
and they're saying these set of PTSD
symptoms are finally gone and so this
idea that for whatever reason going into
what's probably a highly plastic state
and reexperienced memories and then as
you you know, you know, we we
reconsolidating it in that state for
whatever reason um may drive um drive a
therapeutic effect. My business is to
find treatments that help people. And so
I'm much more like pragmatic about it.
You know, if if this sort of thing,
which um has a lot of cultural baggage,
um but if this sort of thing ultimately
ends up being therapeutic, if we can
design trials that convince me and
others that it is, then we should
absolutely use it. And if it doesn't,
then we clearly shouldn't use it, right?
The work that's been done so far, the
first psilocybin trial, um the first
MDMA trial that's published in nature
medicine recently. Um
>> and what do those generally say? Let's
let's uh start with psilocybin and MDMA.
So MDMA appears to in in um you know one
to a few MDMA sessions have an anti-PTSD
effect that seems to be you know um
outside of the kind of um standard
assumed levels of PTSD improvement that
you can observe in individuals um with
this level of PTSD. Right? So,
>> so does that mean that um for people
that have trauma who do a and again
we're talking about in a clinical
setting they they take a one or two
doses of of MDM I think the standard
MAPS dose is 150 to 175 milligrams again
doing this with a physician etc control
clinical trial legal
>> exactly
>> they do it once or twice and broadly
speaking what percentage of people who
had trauma report feeling significant
relief from their tra trauma afterward
>> it's about twothirds of people had a had
um a clinically significant uh change in
their PTSD.
>> That's impressive. And how how
longasting was that?
>> It appears to last for a while. In the
earlier trials where they followed
people out, it seemed to last for kind
of in the years range for some people.
And so it's, you know, it's pretty it's
pretty compelling. In contrast that with
ketamine, which only on average lasts
about a week and a half for a single
infusion. So it's a much shorter.
>> So they have to get repeated infusions
of ketamine every 10 days or so
>> for some people. or they end up getting
like like like a bunch of doses for a
couple of weeks and then for some people
that seems to last a while. Um you know
that's where I think I think the the
psilocybin story for depression and the
um in the MDMA story for PTSD seem more
interesting to me.
>> So for psilocybin what is the um rough
percentages on and this would be relief
not from trauma but from depression.
>> Yeah. Exactly. So it's, you know, in
open label studies, it's closer to like
half to 2/3 of people end up getting
better depending upon their level of
treatment resistance. In the in the
blinded trials, it was more like a third
or so of people.
>> Since you mentioned psilocybin, let's
talk a little bit about the
neurochemistry of psilocybin. What's
going on when one takes psilocybin and
um why is it interesting in light of
depression?
>> Yeah, definitely. So David Nut and Robin
Card Harris's work around neuroiming
psychedelics were kind of the some of
the first folks to do that work and um
you know and to their great surprise
they thought there was going to be an
increase in activity on psychedelics and
what they found is the opposite right
there's kind of a an overall decrease in
the level of activity in the brain um
with psychedelics but they they've also
looked at connectivity and there's this
kind of small world you know large world
connectivity that you you think about
and So you know small world meaning
there's a lot there's kind of a much
more kind of focused kind of cortical
function or you know subcortical
function or whatever it is and uh and
what you see is a difference in that um
in that level of engagement of of brain
regions the connectivity kind of global
connectivity kind of increases and so
it's interesting you know I think to to
kind of have a convergent theory on this
it's still you know to be determined
there's still a lot of work I think that
needs to be done. But um but it's
certainly um suggestive that there's
pretty profound changes in um in brain
activity and brain connectivity after.
And what we found to be really
interesting is the the anti-depressant
effects of psilocybin
have a particular um connectivity change
that we also see with our our TMS
approaches, right? And it's this
connectivity between the subgenial
anterior singulate and the default mode
network. And so when we do this
effective Stanford neurom modulation
therapy stimulation, we see a down
reggulation the connectivity between the
negatively valanced mood state in the
case of depressed individuals and the
self-representation of the brain. And
you see that same connectivity change
occur posts psilocybin,
you know, suggesting there's a
convergent mechanism. And it makes
sense, right? you've kind of got an
overconnected negatively balanced
system, conflict system that's kind of,
you know, kind of attached on to the
self-representation and people feel
stuck, right? And then when you when you
do whatever you do that's effective, it
it unpairs those two systems.
>> I want to ask you about Ibagane. Is it
legal in the US in terms as a clinical
tool? Who's using it and for what
purposes? Ibugane is a um is one of the
alkaloids that you can extract from a um
an ibogga tree root bark that's um
typically growing in the country of
Gabon Africa. So what uh individuals
taking ibeame will say is that open eyes
they don't see anything but closed eyes
they'll go back through and reexperience
earlier life memories and they will be
able to experience it from a place of
empathy not only for themselves but from
others and kind of a detached empathy
and being able to see this as almost a
third party even though they were there.
Ibegan is in no way a recreational
substance. You're essentially having
this what they call a life review. They
also call it 10 years of psychotherapy
in a night. So these are the terminology
that people talk about the issue.
>> How long does it last? Is it truly one
night
>> depending upon how fast you metabolize
it? Sometimes 24, sometimes 36 hours,
sometimes it can be shorter. But it is a
long time.
>> Wow.
>> It's a very long time. So it's it's
definitely the longest acting
psychedelic substance I know of. And so,
you know, we have over the last couple
of years been able to um to do this
first in human kind of full
neurobiological clinical neurocognitive
evaluation of what I is doing in this
case in in uh special operations,
special forces individuals, former Navy
Seals, former Army Rangers, that that
kind of crew of folks and look at the
pre-post changes that we um that they're
experiencing and be able to totally
quantitate all of that and so we've been
able to capture all the clinical scales
you know depression scales PTSD scales
all that standard stuff neurokcognitive
batteries so how does your executive
function work specifically how does your
verbal memory all of that and then neuro
imaging and EEG so this will be the
first human study of ibugane for those
and the reason why is because I gain
kind of the both seemingly the most
potent and most um
in and mo seemingly to me at least most
powerful um psychedelic, but the the one
that has the most risk too because it
has a cardiac effect. It seems to be
that you can screen people out that have
risk off of their electroc cardiogram
and and reduce the risk quite a bit and
that's what we we all did. But um but
but that's why people haven't really
studied it as much. Um and it's it isn't
as uh in addition there's nobody goes to
rave on ibain. There's no recreation at
all with it.
>> It's not fun. People say that it's
relieving, but it's hard work, right?
Because yeah, you're re you're
re-examining things. So then we see
these folks after and I I'll tell you,
you know, we haven't fully analyze the
data yet, but I'll tell you that from
what my folks are telling me, it's
pretty dramatic. You know, people come
back and they're doing a lot better.
Soldiers experience something called
moral injury, right? Where they maybe
they accidentally blew something up and
it had a kid in it or something like
that. you know, you know, if they're in
Afghanistan or Iraq, maybe, you know, a
child died on accident or maybe maybe,
you know, a civilian died or whatever it
was, right? And they and they suffer
these moral injuries as part of the job.
And it's almost one of the kind of, you
know, vocational risks. They come back
and say that they've they've they've um
forgiven themselves, you know, which is
which is huge, right? And and part of
that is being able to see themsel in a
different light and having empathy
finally for themsel and being able to
kind of have that experience of
forgiving. And so there's this kind of
Timothy Liry kind of socioultural
construct that ends up being overlaid
over psychedelics. And what I think is
that if you rid yourself of all of those
preconceived notions of what it is and
isn't and the counterculture movement,
all that stuff that neither of us were
ever involved in, neither of us are ever
partake in, you know, as is kind of
straight scientists looking at this,
right? If you can kind of rid yourself
of all those socioultural constructions
and then re-examine this, these if we
just discovered these today, we would
say that these sorts of drugs are a huge
breakthrough in psychiatry because they
allow for us to do a lot of the sorts of
things we've been thinking about with
with SSRIs, with psychotherapy, but kind
of combined, right? psychotherapy plus
plus plus drugs in a in a substance that
kind of allows you to reexamine these
things. And so it's it's interesting.
It'll you know there's a lot to do to
try to figure out if that's true, you
know, and and I can say that as it
stands right now, we don't know if it's
that statement is true, right? There's a
lot more work that needs to happen for
that statement to be proven to be true.
But the hypothesis is if it is true then
it's very likely that
this will be seen as a breakthrough
because it allows you to do these sorts
of things that you can't do with normal
waking consciousness.
But also why we have to really think
about this and you know these drugs
can't be recreational drugs. They really
shouldn't be recreational drugs, right?
they're really too powerful to be used
in the context of recreation because
they can put you into these states and
and the this generation of psychedelic
researchers are really clear about that.
You know, I think the ' 60s folks were
not clear about that and they they felt
like there was this whole kind of
cultural thing that was going on there.
But I think this cohort of individuals
really understands that in order to
really make this happen, we have to
understand that if you need a
prescription for an SSRI, which doesn't
change your consciousness a whole lot,
and we we're very worried about that and
the doctor has to evaluate you for that
every week, that the idea that some of
these substances would would go outside
of of very strict medical supervision is
uh is kind of preposterous, actually.
It's kind of it's kind of a a dumb
moment, I think, for for all of medicine
to say, "Look, we've, you know, if we're
going to do this right, we've got to do
it in such a way that's so protected,
that's so safe that we make sure people
know these things are not recreational,
and they're really for the pure purposes
of of really powerfully changing um
cognition for a while and letting people
have these what seem to be, you know,
relatively therapeutic states. Tell me
about Iawaska um and as a plant. Is it
useful for the same sorts of conditions
that we've talked about um thus far? And
if you could um perhaps tell me a little
bit also about the um Brazilian prisoner
study.
>> Yeah,
>> definitely. IA is another psychedelic.
It's used as a sacrament um in um in
Brazil and um in Peru and Ecuador and
Colombia. So a lot of the South American
countries and um and what they do is
they combine two plants together where
one plant of the two plant combination
would effectively do nothing but the two
plant combination together is capable of
producing this very profound psychedelic
effect. And what's really kind of
curious is that there are, as I
understand it, 10 to 20,000 plant
species in the Amazon. And somehow
somebody
>> someone tried them all
>> combined these two plants together in
certain proportionality
and cooked this for five 10 hours to the
point where you cook out the
dimethylryptamine out of one of the
plants and cook out the reversible
monoamine oxidase inhibitor out of the
other plant. It's such a way that the
reversible monoamine oxidase inhibitor
prevents the the GI breakdown of the
dimethylrypamine in such a way that it's
then allowed to cross the bloodb brain
barrier and get into the brain. And if
you didn't add the reversible monomine
oxidase inhibitor plantder derived into
this combination then it would never
cross the brain. If you put people on a
standard psychiatry prescribed
monoimmune oxidase inhibitor that wasn't
reversible, you'd throw them into
serotonin syndrome. Right? So this kind
of like sweet spot that somehow I
practitioners have found of being able
to get DMT into the brain from an oral
source with this combination of a
monomine oxidase inhibitor. It's
curious. Um and so that that substance
has been explored as an anti-depressant
agent and some studies have looked at
that. It also seems to be very safe
there. Um there was a there's a
psychiatrist down at um UCLA Harbor
who's done a lot of work with this where
um where he's looked at children even
that have been exposed to to kind of
small doses of Iawaska as is kind of a
sacrament within Amazonian tribes and
found no neurocognitive effects, no
neurocognitive effects in adults. And so
it appears to be safe. It's kind of part
and brought into various religions
including kind of merged with
Catholicism in South America which is
kind of very interesting. And so you
know in some
sects of Catholicism in Brazil it's used
as a sacrament during religious um
ceremonies. And so it became interesting
to Brazilian researchers as to whether
or not they could affect recidivism
rates for prisoners in Brazilian
prisons, right? So they gave half of the
prisoners
um you know some sort of inert substance
and half of the prisoners a um an
Iawaska session. And the the uh
recidivism rate or the return to prison
rate in the Iawaska exposed individuals
was statistically significantly lower
than the recidivism rate in the uh in
the control group. suggesting that um
you know whatever is going on there
seems to have an effect on whatever
drives criminal behavior whatever
criminal behavior that happened to be
and I don't have the the details on the
exact nature of the crime. Um you know
no I am also in no way saying that we
should just be giving psychedelics to to
to folks in prison and all of that. I
think that that that that is a very edgy
thing to do and probably not something
that anybody should try. But but it does
it does kind of bring up this this
curious question of of what is it about
that that would drive people to um to
change those behaviors and and why why
do people make those behavioral
decisions?
>> Before we wrap, I do want to give you
the opportunity to talk about the Saint
study.
>> Yeah. Saint or what we're we're calling
it S&T now. Um Stanford accelerated
intelligent neurom modulation therapy or
now what we're calling Stanford neurom
modulation therapy. The idea there is
that TMS um is a device that delivers um
that delivers a treatment and the
treatment is the protocol and the
protocol is the stimulation parameter
set in a specific brain region for a
specific condition. Whether it be
transcranial magnetic stimulation or
transcranial direct current stimulation
or deep brain stimulation like what
Casey Halpern talked about. In all of
those cases, the device itself is a
physical layer conduit of a stimulation
protocol that's therapeutic for a given
condition in a given brain region. We
decided gosh, you know, this problem I
talked about at the beginning of the
show where you have these, you know,
this problem that we we don't have a
treatment for people who are in these
high acuity psychiatric emergency
states, right? this idea that we're
going to engineer a treatment where we
can reorganize the stimulation approach
in time to be much more efficient by
utilizing something called space
learning theory. And so you you probably
know about the space learning theory. So
the idea for the for the viewers is if
I'm cramming for a test, what I do is I
write out 60 note cards and I read each
one for a minute until I get to the
first note card and again and that's
about an hour later, right? That's space
learning theory. It's this idea that you
need to see it about every hour to an
hour and a half and that optimizes
learning. What we found was is that the
old way of doing TMS, this idea of just
doing it once a day, every day, 5 days a
week for 6 weeks, didn't utilize the
space learning theory. It's like
studying for a month or two, just a
little bit once a day. Like you remember
some of that stuff, but it's like not as
potent as that week where you're kind of
cramming, right? And what we realized is
that if we could reorganize the
stimulation in times that we took the
whole six week course, we actually
figured out a way to do it in a day. And
then what we also figured out is that
people were underdosing TMS because if
you just keep going after 6 weeks out to
month three, four, five, more and more
people got better. So we figured out
it's not just one day. We're going to
give five times the normal dose. We're
going to give 7 and 1/2 months worth in
5 days using space learning theory. So
every hour
>> every hour for 10 hours
>> for 5 days
>> for 5 days. So it's a 50-hour block.
It's 90 minutes of actual stimulation
but spread out through the day in the
same way of learning. What we've found
is that folks will um will within one to
five days, you know, in in more cases
than not, depending upon if you're
looking at this open label or in trials,
somewhere between 60 and 90% of the
time, they will go into full-on
remission in the sense they're totally
normal from a mood standpoint at the end
of this. And like I said, with variable
dur durability. So that's the part we
have to figure out now about dosing and
how to keep people well. But for some
people, you know, we've had four years
of remission, you know, a year of
remission. And it's it's really that
cramming of the test. It's really that
idea that you're laying in that
information to the exact right spot. And
the the signal is a simple signal, but
it's a profound one, which is turn on,
stay on, remember to stay on. You know
that idea that you're si you're sending
this memory signal into the brain and
you're doing it in such a way that
you're telling the system you're kind of
taking it out of the hippocampus's hand
your own hippocampus' hand and you're
sending the same signal the hippocampus
normally signals out. Now you're sending
that signal into the prefrontal cortex
and kind of utilizing the brain's own
communication style to get it to get out
of this state. And what's very cool
about this is that um is that people
when they when they kind of exit out of
that, they end up um they end up saying
they don't have any any side effects
from it and they feel back to normal.
>> Thank you so much uh for taking us on
this incredible voyage through the
neurosircuitry underlying certain
aspects of depression, the coverage of
the different types of depression, the
various uh therapeutic compounds, how
they work. We've um talked about a lot
of things today and you you've shared so
much knowledge and even as I say that I
um I very much want to have you back to
talk about many other things as well
that we didn't have time to cover. But
to take the time to sit down with us and
share all this knowledge that really is
in service to mental health and and
human feeling better and in fact
avoiding often suicidal depression. It's
just incredible work and an incredible
generosity and just thank you so much.
>> Absolutely. Thank you.