Huberman Lab - Essentials: Understanding & Healing the Mind | Dr. Karl Deisseroth
Episode Date: May 15, 2025In this episode of Huberman Lab Essentials, my guest is Dr. Karl Deisseroth, M.D., Ph.D., a clinical psychiatrist and professor of bioengineering and of psychiatry and behavioral sciences at Stanford ...University. We discuss his experiences as a clinician treating complex psychiatric conditions and his lab’s pioneering work in developing transformative therapies for mental illness. He explains the complexities of mental illness and how emerging technologies—such as optogenetics and brain-machine interfaces—could revolutionize care. We also explore promising new therapies, including psychedelics and MDMA, for conditions like depression and PTSD. Read the episode show notes at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman David: https://davidprotein.com/huberman Eight Sleep: https://eightsleep.com/huberman Timestamps 00:00:00 Karl Deisseroth; Neurology vs Psychiatry 00:01:36 Speech; Blood Test?; Seeking Help 00:04:20 Feelings, Jargon; Psychiatric Treatment 00:09:40 Sponsor: David 00:10:55 Future Treatment; Vagus Nerve Stimulation, Depression, Optogenetics 00:19:40 Brain-Machine Interfaces 00:20:53 Sponsor: Eight Sleep 00:23:00 ADHD Symptoms, Lifestyle, Technology 00:29:34 Psychedelics, Depression Treatment, Risks 00:35:43 Sponsor: AG1 00:37:30 MDMA (Ecstasy), Trauma & Post-Traumatic Stress Disorder (PTSD) Treatment 00:40:33 Projections: A Story of Human Emotions Book, Optimism Disclaimer & Disclosures
Transcript
Discussion (0)
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.
And now my conversation with Dr. Karl Deisseroth.
Well, thanks for being here.
Thanks for having me.
So for people that might not be so familiar
with the fields of neuroscience, et cetera,
what is the difference between neurology and psychiatry?
Psychiatry focuses on disorders where we can't see
something that's physically wrong,
where we don't have a measurable,
where there's no blood test that makes the diagnosis.
There's no brain scan that tells us this is schizophrenia,
this is depression for an individual patient.
And so psychiatry is, is much more mysterious.
And the only tools we have are words.
Neurologists are fantastic physicians.
They see the stroke on brain scans.
They see the seizure and the pre-seizure activity with an EEG.
And they can measure and treat based on those measureables.
In psychiatry, we have a harder job.
We use words, we have rating scales for symptoms, we can measure depression and autism with
rating scales, but those are words still.
And ultimately that's what psychiatry is built around. It's an odd situation because we've got the most complex,
beautiful, mysterious, incredibly engineered object
in the universe, and yet all we have are words
to find our way in.
So do you find that if a patient is very verbal
or hyperverbal, that you have an easier time diagnosing them
as opposed to somebody who's more quiet and reserved, or I can imagine the opposite might be true
as well.
Well, because we only have words, you've put your finger on a key point.
If they don't speak that much, in principle, it's harder.
The lack of speech can be a symptom.
We can see that in depression.
We can see that in the negative symptoms of schizophrenia.
We can see that in autism. Sometimes by see that in the negative symptoms of schizophrenia, we can see that in autism.
Sometimes by itself that is a symptom of reduced speech, but ultimately you do need something.
You need some words to help guide you.
And that, in fact, there's challenges that I can tell you about where patients with depression
who are so depressed they can't speak, that makes it a bit of a challenge to distinguish depression
from some of the other reasons they might not be speaking.
And this is a sort of the art and the science of psychiatry.
Do you think you will ever have a blood test
for depression or schizophrenia or autism?
And would that be a good or a bad thing?
I think ultimately there will be quantitative tests. Already efforts are being made to look at certain rhythms in the brain using external EEGs,
to look at brain waves effectively.
But ultimately what's going on in the brain in psychiatric disease is physical,
and it's due to the circuits and the connections and the projections in the brain
that are not working as they would in a typical situation.
And I do think we'll have those measurables at some point.
Could it be abused or misused?
Certainly, but that's, I think, true for all of medicine.
I wanna know, and I'm sure there are several,
but what do you see as the biggest challenge
facing psychiatry and the treatment of mental illness today?
I think we have, we're making progress on what the biggest challenge is, which I think
there's still such a strong stigma for psychiatric disease that patients often don't come to
us and they feel that they should be able to handle this on their own.
And that can slow treatment.
It can lead to, you know, worsening symptoms.
We know, for example, patients who have untreated anxiety issues, if you go for a year or more
with a serious untreated anxiety issue, that can convert to depression.
You can add another problem on top of the anxiety. And so,
it would be, you know, why do people not come for treatment? They feel like this is something they
should be able to master on their own, which can be true, but usually some help is a good thing.
That raises a question related to something I heard you say many years ago at a lecture,
which was that this was a scientific lecture and you said, you know, we don't know how other people
feel. Most of the time we don't even really know how we feel. You could elaborate on that a little
bit and the dearth of ways that we have to talk about feelings.
I mean, there's so many words, I don't know how many,
but I'm guessing there are more than a dozen words
to describe the state that I call sadness.
But as far as I understand,
we don't have any way of comparing that
in a real objective sense.
So how, as a psychiatrist,
when your job is to use words to diagnose,
words of the patient to diagnose,
do you maneuver around that?
And what is this landscape that we call feelings or emotions?
This is really interesting.
People, here we have it, there's a tension between the words
that we've built up in the clinic
that mean something to the physicians.
And then there's the colloquial use of words
that may not be the same. And so that's the colloquial use of words that may not be the same.
And so that's the first level we have to sort out when someone says, you know, I'm depressed,
what exactly do they mean by that?
That may be different from what we're talking about in terms of depression.
So part of psychiatry is to get beyond that word and to get into how they're actually
feeling, get rid of the jargon and get to
real world examples of how they're feeling.
So how much do you look forward into the future?
How much hope do you have?
How much planning are you doing for the future?
So here now you're getting into actual things you can talk about that are unambiguous. If someone says, yeah, I can't even think about tomorrow.
I don't see how I'm going to get to tomorrow.
That's a nice, precise thing that it's sad, it's tragic, but it's also that means something
and we know what that means.
That's the hopelessness symptom of depression.
And that is what I try to do when I do a
psychiatric interview, I try to get past the
jargon and get to what's actually happening in the
patient's life and in their mind.
But as you say, ultimately, you know, this shows up
across, I, I address this issue every day in my life,
whether it's in the lab where we're looking at
animals, whether fish or mice or rats and studying their behavior or
when I'm in a conversation with just a friend or a colleague or when I'm
talking to a patient, I never really know what's going on inside the mind of the
other person. I get some feedback, I get words, I get behaviors, I get
actions, but I never really know.
Are there any very good treatments
for psychiatric disease?
Meaning are there currently any pills, potions,
forms of communication that reliably work every time
or work in most patients?
And could you give a couple of examples
of great successes of psychiatry if they exist?
Yes, and psychiatry, despite the depths of our,
the mystery we struggle with,
many of our treatments are actually, you know,
we may be doing better than some other specialties
in terms of actually causing, you know,
the therapeutic benefit for patients.
We do help patients, you know,
patients who suffer from, by the way,
both medications and talk therapy have been shown
to be extremely effective in many cases.
For example, people with panic disorder, cognitive behavioral therapy, just working with words,
helping people identify the early signs of when they're starting to move toward a panic
attack, what are the cognitions that are happening.
You can train people to derail that and you can very potently treat panic disorder that
way.
There are many psychiatric medications that are very effective for the conditions that
they're treating.
Anti-psychotic medications, they have side effects, but boy do they work.
They really can clear up auditory hallucinations, the paranoia.
And then, you know, this is a frustrating and yet heartening aspect of psychiatry. There are treatments like electroconvulsive therapy, which is extremely effective for
depression.
We have patients who nothing else works for them, where they can't tolerate medications,
and you can administer under a very safe, controlled condition where the patient's
body is not moving. They're put into a very safe situation where condition where the patient's body is not
moving, they're put into a very safe situation where the body doesn't move or seize.
It's just an internal process that's triggered in the brain.
This is an extraordinarily effective treatment for treatment-resistant depression.
At the same time, I find it as heartening as it is to see patients respond to this with
a, who have severe depression, I'm also frustrated by it.
Why, why can't we do something more precise than, than this
for these very severe cases? In all of these cases though, in psychiatry,
the, the frustrating thing is that we don't have
the level of understanding that a cardiologist has in thinking about the
heart. You know, the heart is, we now know it's a pump, it's pumping blood.
And so you can look at everything about how it's working
or not working in terms of that frame.
It's clearly a pump.
We don't really have that level of what,
what is the circuit really there for in psychiatry.
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What are the pieces that are going to be required
to cure autism, cure Parkinson's, cure schizophrenia?
I would imagine there are several elements and bins here,
understanding the natural biology,
understanding what the activity patterns are,
how to modify those.
Maybe you could just tell us what you think,
what is the bento box of the perfect cure?
Yeah, I think the first thing we need is understanding.
What is the elements in the brain that's analogous to the pumping part?
When we think about the symptoms of depression, that's maybe, you know, we think about motivation
and dopamine neurons.
And so then that turns our attention as neuroscientists.
We think, okay, let's think about the parts of the brain that are involved in dealing with merging complex data
streams that are very high in bitrate that need to be fused together into a unitary concept.
And that starts to guide us and maybe we can and we know other animals are social in their
own way and we can study those animals. And so that's how I think about it. There's hope
for the future thinking about the symptoms as an engineer might,
and trying to identify the circuits that are likely working
to make this typical behavior happen.
And that will help us understand how it becomes atypical.
We need to know the circuits.
We need to know the cells in the various brain regions
and portions of the body and how they connect to one another
and what the patterns of activity are under a normal,
quote unquote, healthy interaction.
If we understand that, then it seems that the next step,
which of course could be carried out in parallel, right?
That work can be done alongside work
where various elements within those circuits are tweaked just right,
like the tuning of a piano in the subtle way, or maybe even like the replacement of a whole
set of keys if the piano is lacking keys, so to speak.
In 2015, there was this, what I thought was a very nice article published in the New Yorker
describing your work and the current state of your work in the laboratory, in the clinic,
and an interaction with a patient.
So this is, as I recall, a woman who was severely depressed
and you reported in that article,
some of the discussion with this patient.
And then in real time,
increase the activation of the so-called vagus nerve,
this 10th cranial nerve that extends out of the skull and innervates many of the viscera and body. What is the potential for channel rhodopsins
or related types of algae engineering to be used to manipulate the vagus?
Because I believe in that instance, it wasn't channel opson stimulation, it was electrical
stimulation, right? Or to manipulate, for instance,
a very small localized region of the brain.
Let me frame it a little bit differently
in light of what we were talking about
a couple of minutes ago.
My understanding is that if somebody has severe depression
and they take any number of the available
pharmaceutical agents that are out there,
SSRIs, serotonin or JIC agents,
increase dopamine, increase whatever,
that sometimes they experience relief,
but there are often serious side effects.
Sometimes they don't experience relief,
but as I understand it, channel opsins
and their related technology in principle
would allow you to turn on or off the specific regions
of the brain that lead to the depressive symptoms,
or maybe you turn up a happiness circuit
or a positive anticipation circuit.
Where are we at now in terms of bringing this technology
to the nervous system?
And let's start with body and then move into the skull.
Yeah, so starting with the body is a good example
because it highlights the opportunity and
how far we have to go.
So let's take this example of vagus nerve stimulation.
So the vagus nerve, it's the 10th cranial nerve.
It comes from the brain.
It goes down.
It innervates the heart, innervates the gut.
By innervate, I mean it sends little connections down to help guide what happens in these organs
in the abdomen
and chest.
It also collects information back, and there's information coming back from all those organs
that also go through this vagus nerve, the 10th cranial nerve, back to the brain.
And so this is somewhat of a superhighway to the brain then, was the idea.
And maybe the idea is maybe we could put a little cuff,
a little electrical device around the vagus nerve itself.
So a way of getting into the brain
without putting something physical into the brain.
And why the vagus?
I mean, it's there, but, and it's accessible.
That's the reason.
That's the reason?
That's the reason, yes.
Really? Yeah.
You're not kidding.
I'm not kidding.
So stimulating the vagus to treat depression simply because it's accessible. That's the reason? That's the reason, yes. Really? Yeah. You're not kidding. I'm not kidding.
So stimulating the vagus to treat depression
simply because it's accessible.
It started as actually as an epilepsy treatment
and it can help with epilepsy,
but the vagus nerve lands on a particular spot
on the brain called the solitary tract nucleus,
which is just one synapse away from the serotonin
and dopamine and the norepinephrine.
So there's a link to chemical systems in the brain
that make it a rational choice.
Yes, it's not irrational, but I can tell you
that even if that were not true,
the same thing would have been tried.
You guys would have done it anyway.
Because it's accessible, yeah.
How do you think it's working when it does work?
Is it triggering the activation of neurons
that release more serotonin or dopamine?
It could be, but I would say we don't have evidence
for that, and so I just don't know.
But what is clear is that it's dose limited
in how high and strongly we can stimulate and why,
it's because it's an electrode
and it's stimulating everything nearby.
And when you turn on the vagus nerve stimulator,
the patient's voice becomes strangulated and hoarse.
They can have trouble swallowing.
They can have trouble speaking for sure, even some trouble breathing because everything
in the neck, every electrically responsive cell and projection in the neck is being affected
by this electrode.
And so you can go up just so far with the intensity and then you have to stop. So you know to your initial question could a more precise stimulation method like optogenetics
help in this setting?
In principle it could because that would if you would target the light sensitivity to
just the right kind of cell, let's say cell X that goes from point A to point B that you
know causes symptom relief of a particular kind,
then you're in business.
You can have that be the only cell that's light sensitive.
You're not gonna affect any of the other cells,
the larynx and the pharynx
and the projections passing through.
So that's the hope, that's the opportunity.
The problem is that we don't yet have
that level of specific knowledge.
We don't know, okay, it's the cell starting in point A,
going to point B that relieves this particular symptom.
We wanna fix this key on the piano.
I'm imagining a little tiny blue light emitting
thing object that's a little bigger than a clump of cells,
or maybe about the size of a clump of cells.
So we're talking about a little tiny stamp,
each edge half a millimeter in size.
I can imagine that being put under my skin.
And then I would, what I hit an app on my phone
and I'd say, I'd say, Dr. Diceroth,
I'm not feeling great today.
Can I increase the stimulation?
And you say, go for it.
And then I ramp it up.
Is that how it would go?
I mean, that's effectively what we already do
with the vagus nerve stimulation.
The doctor in this case, and I have this in some of my patients in we already do with the vagus nerve stimulation. The doctor in this case,
and I have this in some of my patients in the clinic,
I do vagus nerve stimulation.
I talk to them, I say, I go through the symptoms.
I use the psychiatric interview
to elicit their internal states.
And then I have a radio frequency controller
that I can dial in.
Right there in real time.
Right there in real time.
You're holding the remote control
essentially to their brain,
although it's remote remote control.
Through a couple steps, but yeah.
And I can turn up the frequency,
I can turn up the intensity,
all with the radio frequency and control.
And then it's reprogrammed or redosed.
And then the patient can then leave at this altered dose.
In most patients, I don't expect an immediate mood change.
What I do is I increase the dose until a next level up
while asking the patient for side effects.
Can you still breathe okay?
Can you still swallow okay?
And I can hear their voice as well.
And I can get a sense-
And you're looking at their face.
And I'm looking at their face.
And so I can get a sense, is there a,
am I still in a safe side effect regime? And I, and, and, and,
and then, you know, I, I, I stop at a particular point that
looks safe and then patient goes home, comes back a month
later and I get the report on how things were over that
month.
That's very exciting. What are your thoughts about brain
machine interface is something that's been happening for a long time now, devices,
little probes that are going to stimulate different patterns of activity and ensembles of neurons?
First of all, it's an amazing scientific discovery approach. As you mentioned, we and others here at
Stanford are using electrodes, collecting information from tens of thousands of neurons,
even separate from the Neuralink work. As you point out, many people have been doing this in humans as well as in non-human primates.
And this is pretty powerful. It's important. This will let us understand what's going on in the brain
in psychiatric disease, in neurological disease, and will give us ideas for treatment. I see that as something that will be part of psychiatry in the long run.
Already with deep brain stimulation approaches, we can help people with psychiatric disorders
and that's putting just a single electrode, not even a complex closed loop system where you're both
playing in and getting information back,
even just a single stimulation electrode in the brain
can help people with OCD, for example, quite powerfully.
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One of the questions I get asked a lot is about ADHD
and attention deficit of various kinds.
I have the hunch that one reason I get asked so often
is that people are feeling really distracted
and challenged in funneling their attention
and their behavior.
But, and there are a number of reasons for that, of course,
but what is true ADHD and what does it look like?
What can be done for it?
And what, if any, role for channel opsins
or these downstream technologies that you're developing,
what do they offer for people that suffer from ADHD
or have a family member that suffers from ADHD?
Yeah.
This is a pretty interesting branch of psychiatry.
There's no question that people have been helped
by the treatments.
There's active debate over what fraction of people
who have these symptoms can or should be treated.
This is typically adderall or stimulants of some kind.
For example, the stimulants, that's right.
So ADHD, as its name suggests, it has symptoms of,
it can have either a hyperactive state
or an inattentive state.
And those can be completely separate from each other.
You could have a patient who effectively
is not hyperactive at all,
but can't remain focused on what's going on around them.
So their body can be still,
but their mind is darting around.
That's right.
Or they can be very hyperactive with their body.
Yeah, it happens both ways.
Probably rarely is somebody hyperactive with their body,
but their mind is still.
I notice I have to think complex abstract thoughts.
I notice I have to be very still.
So my body has to be almost completely unmoving for me to think complex abstract thoughts. I notice I have to be very still. So my body has to be almost completely unmoving
for me to think very abstractly and deeply.
Other people are different.
Some people when they're running
and they get their best thoughts.
I can't even imagine that.
My brain does not work that way at all.
I have to be totally motionless,
which is kind of interesting.
How do you go about that?
I sit much like this.
I try to have time in each day where I am literally sitting almost in
this position, but without distraction and thinking.
And so it's kind of a, it's almost meditative in some ways, except it's not
true meditation, but I am thinking while not moving.
You're trying to structure your thoughts in that time.
Yeah.
Interesting.
Yeah. So, but everybody, as you say, is very different. And so with ADHD, you have,
the key thing is we want to make sure that this is present across different domains of life,
school and home to show that it really is a pervasive pattern and not something specific to
Oh, you know the teacher or the home situation or something and then you can help patients
It's interesting that that ADHD is one of those disorders where people are trying to work on quantitative EEG based to diagnoses
And so there's some progress toward
Making up a diagnosis with looking at particular externally detectable brainwave rhythms.
So skull cap with some electrodes
that don't penetrate the skull.
That's right.
And this can be done in an hour or two hour session.
That's right.
Has to be done in the clinic, right?
Yeah, in the clinic, right?
You have to have the right recording apparatus and so on.
But that's in principle as you increasing confidence comes
in exactly which measurements one could even imagine
moving towards home tests, but we're not there yet.
Amazing.
I think one of the reasons I get asked about it
so much as a lot of people wonder if they have ADHD.
Do you think that some of the lifestyle factors
that inhabit us all these days
could induce a subclinical or a clinical like ADHD.
Meaning if I look at people's phone use, including my own,
and I don't think of it like addiction,
it looks to me and feels to be more like OCD.
And I'll come clean here by saying when I was younger,
when I was a kid, I had a grunting tick.
I used to hide it.
I actually used to hide in the closet
because my dad would make me stop.
And I used to, I couldn't feel any relief of my mind
until I would do this.
And actually now, if I get very tired,
if I've been pushing long hours, it'll come back.
I was not treated for it,
but I will confess that I've had the experience of,
I always liked sports where I involved a lot of impact,
fortunately not football,
because I went to a high school
where the football team was terrible.
Maybe that would have avoided more impact,
but things like skateboarding, boxing,
they bring relief.
I feel clarity after a head hit, which I avoid,
but I used to say,
that's the only time I feel truly clear for a long,
and then eventually it dissipated.
By about age 16, 17,
it just disappeared.
So I have great empathy for those that feel
like there's something contained in them
that won't allow them to focus on what they wanna focus on.
And these days with the phone and all these email, et cetera,
I wonder and I empathize a bit when I hear people saying
like,
I think I might have ADHD or ADD.
Do you think it's possible that our behaviors and our interaction with the sensory world,
which is really what phones and email really are, could induce ADD or reactivate it?
Yeah, this is a great question. I think about it a lot.
And you mentioned this tick-like behavior
in yourself. It's very common that people who have ticks have this building up of something
that can only be relieved by executing the tick, which can be a motor movement or vocalization
or even a thought. People do, I think these days, do have this, if they haven't checked
their phone in a while, they do have a buildup, a have this, if they haven't checked their phone
in a while, they do have a buildup, a buildup, a buildup until they can check it and relieve
it.
And there's some similarities, you know, there is a little reward that comes with the checking.
But the key question in all of psychiatry, what we do is we don't diagnose something
unless it's disrupting what we call social
or occupational functioning.
You could have any number of symptoms, but literally every psychiatric diagnosis requires
that it has to be disrupting someone's social or occupational functioning.
And these days, checking your phone is pretty adaptive.
That pretty much helps your social and occupational functioning.
And so we can't make it a psychiatric diagnosis.
At least in the world of today.
I'd love your thoughts on psychedelic medicine,
putting them into patients
and seeing tremendous positive effects,
but also tremendous examples of induced psychiatric illness.
In other words, many people lost their minds
as a consequence of overuse of psychedelics.
I'll probably lose a few people out there,
but I do wanna talk about what is the state
of these compounds, and I realize it's a huge category
of compounds, but LSD and psilocybin, as I understand,
trigger activation of particular serotonin receptor
mechanisms may or may not lead to more widespread
activation of the brain more that one wouldn't see otherwise.
But when you look at the clinical
and experimental literature,
what is your sort of top contour sense
of how effective these tools are going to be
for treating depression?
Well, you're right to highlight both the opportunity
and the peril that is there.
And of course we want to help patients.
And of course we want to explore anything
that might be helpful,
and but we want to do it in a safe and rigorous way.
But I do think we should explore these avenues.
These are agents that alter reality
and alter the experience of reality, I should say, in relatively precise ways. They do have
problems. They can be addictive. They can cause lasting change that is not desirable.
Now, that said, even as these medications exist now, as you know, there's an impulse
to use them in very small doses and to use them as adjunctive treatments for the therapy
of various kinds.
And I'm also supportive of that if done carefully and rigorously.
Of course, there's risk, but there's risk with many other kinds of treatment. And I'm not sure that the risks for these medications vastly outweigh the risks that
we normally tolerate in other branches of medicine.
Why would they work?
I mean, let's say that indeed their main effect is to create more connectivity, at least in the moment between brain areas.
So psychedelics seem to be a trajectory not too far off from the dream state where space
and time are essentially not as rigid. And there is this element of synesthesia, of blending of the senses, you know, feeling colors and hearing light and things of that sort.
You hear these reports anyway.
Why would having that dreamlike experience
somehow relieve depression long-term?
Do we have any idea why that might be?
Long term do we have any idea why that might be?
We have some ideas and no no deep understanding one way I think about the psychedelics is they
Increase our willingness to are they've increased the willingness of our brain to accept unlikely
Ways of constructing the world unlikely hypotheses as it were as to what's going on. The brain, in particular our cortex, I think is a hypothesis generation and testing machine. It's
coming up with models about everything. It's got a lot of bits of data coming in and it's
making models and updating the models and changing them, theories, hypotheses for what's going on.
And some of those never reach our conscious mind.
And this is something I talk about in projections in the book quite a bit, is many of these are
filtered out before they get to our conscious mind. And that's good. We think how distracted
we'd be if we were constantly having to evaluate all these, you know, hypotheses about, you know,
what kinds of shapes or objects or processes were out there. And so a lot of this is handled before it gets to consciousness. What the psychedelics seem to do
is they change the threshold for us to become aware of these incomplete hypotheses or wrong
hypotheses or concepts that might be noise but are wrong, and so are never allowed to get into our conscious mind.
Now, you know, that's pretty interesting,
and it goes wrong in psychiatric disorders,
I think in schizophrenia,
sometimes the paranoid delusions that people have
are examples of these poor models
that escape into the conscious mind
and become accepted as reality
and they never should have gotten out there.
Now, how could something like this in the right way
help with something like depression?
Patients with depression often are stuck.
They can't look into the future world of possibilities as effectively.
Everything seems hopeless.
And what does that really mean?
They discount the value of their own action.
They discount the value of the world at giving rise to a future that matters.
Everything seems to run out,
like a river just running out into a desert and drying up.
And what these agents may do that increase the flow
through circuitry, if you will,
the percolation of activity through circuitry
may end up doing for depression is increasing
the escape of some tendrils of process, of forward progression through the world.
That's a concept. That's how I think about it. There are ways we can make that rigorous. We
can indeed identify in the brain by recording. We can see cells that represent steps along a
path and look into the future. And we can rigorously define these cells
and we can see if these are altered on psychedelics.
And so that's one of the reasons that we're working
with these agents in the laboratory to say,
is this really the case?
Are these opening up new paths
or representations of paths into the future?
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MDMA, ecstasy is a unique compound
in that it leads to big increases in brain levels
of dopamine and serotonin simultaneously.
And I realized that the neuromodulators
like dopamine and serotonin often work in concert,
not alone the way they're commonly described
in the more general popular discussions.
However, it is a unique compound
and it's different than these serotonergic compounds
like LSD and psilocybin.
And there are now data still emerging
that it might be,
and in some cases can be useful for the treatment of trauma,
PTSD and similar things.
Why would that work?
And a larger question,
perhaps the more important question is psychedelics,
MDMA, LSD, all those compounds,
in my mind, there are two components.
There's the experience you have while you're on them.
And then there's the effect they have after.
People are generating variations of these compounds
that are non-hallucinatory variations.
But how crucial do you think it is to have,
let's stay with MDMA, the experience of
huge levels of dopamine, huge levels of serotonin,
atypical levels of dopamine and serotonin released,
having this highly abnormal experience
in order to be normal again?
Yeah.
I think the brain learns from those experiences.
That's the way I see it.
And so, for example, people who have taken MDMA,
they will, as you say, they'll
have, they'll be the acute phase of being on the drug and experiencing this
extreme connectedness with other people, for example.
And then the drug wears off and, but the brain learned from that experience.
And so what people will report is,
yeah, I'm not in that state, but I saw what was possible.
I saw, yeah, you can, there don't need to be barriers,
or at least not as many barriers as I thought.
I can connect with more people in a way that is helpful.
And so I think it's the learning that happens in that state
that actually matters.
And as you described that, that sounds a lot like
what I understand to be the hallmark feature
of really good psychoanalysis,
that the relationship between patient and therapist
hopefully evolves to the point where
these kinds of tests can be run
within the context of that relationship
and then exported to other relations.
Exactly right, yeah. Is that?
Exactly right.
And that probably, I'm assuming is still the goal of really good psychiatry also.
It's a part of intimacy really.
It should be when we have time, I think all good psychiatrists try to achieve that level
of connection and learning, try to help patients create a new model that is stable, that is learned,
and that can help instruct future behavior.
One of the things that I took from reading your book,
in addition to learning so much science
and the future of psychiatry and brain science was,
amidst these very, it may cause very tragic cases and sadness
and a lot of the weight that that puts on the clinician,
on you also, that there's a central cord of optimism
that where we're headed is not just possible,
but very likely and better.
And, you know, are you an optimist?
I am.
And this is, by the way,
this was a really interesting experience
in writing projections because I had a dual goal.
I wanted it to be for everybody,
literally everybody in the world who wants to read it.
And yet at the same time, I wanted to stay absolutely,
rigorously close to the science, what was actually known.
When I was speaking about science,
when I was speaking about the neurobiology of the brain or psychiatry,
I wanted to not have any of my scientific colleagues think, oh,
he's going too far, he's saying too much. So I had these two goals, which I kept in
my mind the entire time. And a lot of this trying to find exactly the right word we talked
about was on this path of staying excruciatingly rigorous in the science and yet letting people
see the hope, where things were, have everybody
see that we've come a long way, we have a long way to go, but the trajectory and the
path is beautiful.
And so that was the goal.
I think, of course, that sounds almost impossible to jointly satisfy those two goals, but I kept
that in my mind the whole way through.
And yes, I am optimistic, and I hope that came through in the book.
But it certainly did.
And at least from this colleague, you did achieve both.
And it's a wonderful, it's a masterful book really. And one that as a scientist and somebody who is a fellow brain explorer
hits all the marks of rigor and is incredibly interesting.
And there's a ton of storytelling.
Definitely check out the book.
There are other people in our community that of course
are going to be reaching out on your behalf,
but it's incredible that you juggle this enormous number of things.
Perhaps even more important, however, is that it's all in service to this larger thing of relieving
suffering. So thank you so much for your time today, for the book and the work that went into
the book. I can't even imagine for the laboratory work and the development channel ops and clarity
and all the related technologies and and for the clinical work
You're doing it and for sharing with us. Well, thank you for all you're doing and reaching out
I'm very impressed by it. It's important and and it's it's so valuable and thank you for taking the time and for all your gracious
Words about the book. Thank you