0:00

What if you could take the

0:02

drug out of the trip? In

0:04

other words, recreate a

0:06

psychedelic-like experience without

0:09

reference to a

0:11

psychedelic drug itself? Hi.

0:14

I'm Elizabeth Coke. We all

0:16

live inside our own personal

0:18

private perception box. built by

0:21

our genes and the physical,

0:23

social, and cultural environment in

0:25

which we were born and

0:28

raised. In this podcast, we

0:30

explore how although the walls

0:32

of this mental box are

0:35

always present, they can expand

0:37

in states like awe, wonder,

0:39

and curiosity, or contract

0:41

in response to anxiety, fear,

0:44

and anger. I'd like to

0:46

introduce our esteemed hosts. to

0:49

incredible and distinguished minds. Dr.

0:51

Heather Berlin, professor of psychiatry

0:53

and neuroscience at the Icon

0:56

School of Medicine at Mount

0:58

Sinai in New York City. And

1:00

Dr. Kristof Koch, chief scientist for

1:02

the Tiny Blue Dot Foundation,

1:04

and the current meritorious investigator

1:07

and former president of the

1:09

Allen Institute for Brain Science.

1:12

Welcome to the Science of

1:14

Perception Box. Hi

1:18

everybody, welcome to Science of Perception

1:20

Box. I'm your co-host, Dr. Heather

1:23

Berlin. I'm your co-host, Dr. Kristof

1:25

Kaur. So every week we feature an

1:27

aspect of the Science of Perception

1:30

Box, highlighting the latest research together

1:32

with our expert guests. This week

1:34

we're exploring the powerful research

1:36

around psychedelics and dream states

1:38

in the practice of anesthesiology

1:41

with a researcher and doctor

1:43

who has been as fascinated

1:45

about consciousness as we are. Dr.

1:47

Boris Heifitz is a

1:49

board-certified anesthesiologist who specializes

1:51

in providing anesthesia for

1:53

neurological surgery. He's practiced

1:56

at Stanford since 2010.

1:58

In addition to treating pain... Dr.

2:00

Heifitz also directs clinical research and

2:02

basic neuroscience. His research group studies

2:05

how new rapid-acting psychiatric therapies, like

2:07

kenamine, MDMA, and cylacidin, produce lasting

2:09

changes in nervous system function, behavior,

2:12

and therapeutic outcomes. But first we

2:14

want to share our own connection

2:17

to psychedelics. They made me lose

2:19

a sense of self. They made

2:21

me lose my sense of body

2:24

of an external world, but they

2:26

were still consciousness. And they made

2:28

me lose my fear of death.

2:31

Well, that's pretty profound. So do

2:33

you think you're more relaxed person

2:35

law? Yes, certainly. You seem very

2:38

relaxed. Well, Boris, thanks for joining

2:40

us. Thanks for having me. How

2:42

did you become interested in psychedelics

2:45

as an anesthesiologist? So I became

2:47

interested in psychedelics well before I

2:49

became an anesthesiologist. I see. The

2:52

question is how did I become

2:54

interested in anesthesiology as a psychedelics

2:56

explorer? You mean psychonote? Well, I've

2:59

done some research on the topic

3:01

before before becoming a doctor. When

3:03

I was towards the end of

3:06

my PhD training. So I did

3:08

an MD and a PhD at

3:10

Einstein in New York. I had

3:13

this question of like, well, how

3:15

am I going to apply this?

3:17

What we're doing is we're looking

3:20

at synaptic responses in brain tissue,

3:22

we're looking at the inner workings

3:25

of how circuits function in the

3:27

brain. And I didn't want to

3:29

lose that, right? And I wanted

3:32

to pick a specialty that would

3:34

allow me the most access to

3:36

that kind of thinking, that kind

3:39

of environment. And, you know, not

3:41

to mention. this background interest in

3:43

psychedelics. I think when I started

3:46

medical school my mom told me

3:48

drop it. You can't have a

3:50

career. You can't have a career

3:53

studying psychedelics, it's hippiescience. This is

3:55

in 2000, probably good advice. But

3:57

when it came time to pick

4:00

a specialty, I was thinking about

4:02

psychiatry, neurology, neurosurgery, an anesthesiology. And

4:04

the most, the closest I could

4:07

get to applied neuroscience was actually

4:09

an anesthesiology. You give, you give

4:11

a drug, and you see its

4:14

effect on the brain, the body.

4:16

on consciousness itself and that to

4:18

me it never gets old. How

4:21

do you know that consciousness is

4:23

gone as compared to they're unable

4:25

to talk and they're unable to

4:28

signal that they're still there? How

4:30

do you know they're not present?

4:33

So we have a lot of

4:35

interviews with patients after surgery that

4:37

you know are it can attest

4:40

to that is that what's kind

4:42

of remarkable about anesthesia is that

4:44

it's not like sleep. And when

4:47

you close your eyes as you

4:49

go off to, as you are

4:51

anesthetized for surgery, when you open

4:54

them, many patients will feel that

4:56

no time is passed. It's very

4:58

different from when you wake up.

5:01

You kind of have an intuitive

5:03

sense of how long you may

5:05

have slept. So that's already one

5:08

difference. Just at the level of

5:10

what the patient experiences. One of

5:12

the earliest concerns for anesthesia, as

5:15

you know, we were developing anesthetic

5:17

techniques to keep people immobile. and

5:19

pain-free and amnestic, right, during surgery

5:22

is there's something called the Bryce

5:24

questionnaire. What's the last thing you

5:26

remember before going to sleep? What's

5:29

the first thing you remember when

5:31

you wake up? And did you

5:33

have any dreams during anesthesia? Do

5:36

you recall anything? And that's, you

5:38

know, that's basically how we set

5:41

standards for what depth of anesthesia

5:43

we use. So how often does

5:45

it happen that I guess depending

5:48

on the type of anesthesia and

5:50

the duration that people do? Recall

5:52

something that does relate in some

5:55

way to something that did happen

5:57

in the O. So it's around

5:59

one in a... So, awareness under

6:02

general anesthesia, even with EEG monitors.

6:04

So, you know, we're monitoring brain

6:06

function, we're getting a sense of

6:08

the depth, but we're clearly not

6:10

getting the whole picture because every once

6:12

in a while a patient will

6:14

recall something. Now, I want to

6:16

put a qualifier on that before,

6:18

you know, nobody ever has surgery

6:20

again after listening to this podcast.

6:22

I've seen one case like this,

6:25

and in an elderly woman, not who

6:27

I would have expected. And though

6:29

the things she said was everything

6:31

was so far away that everyone

6:34

was touching me really softly,

6:36

but she was recalling conversations in

6:38

the OR, so there's a deep

6:40

disconnection, but she was able to

6:42

maintain some sort of input from

6:44

the real world. So that, again,

6:46

that's one in a thousand. and

6:48

no pain because she didn't complain

6:50

of pain she didn't complain you

6:52

know it was a little bit

6:54

distressing to her because she'd kind

6:56

of she knew what happened but

6:58

she was you know she wasn't

7:00

paralyzed she didn't she the thing

7:02

that I was most worried about

7:04

is did you feel trapped and

7:06

you know thank God she didn't

7:08

and that's again advances in anesthesia

7:10

have allowed us to do surgery without

7:13

paralysis even in some cases So, again,

7:15

this may be a topic for another

7:17

time, but it's, you know, it's

7:19

a rare complication that we

7:21

do worry about. And again,

7:23

that was the early concern

7:25

of anesthesiologist, is that we

7:27

want to make sure that

7:29

consciousness is gone, right? Deep

7:31

disconnection, disconnected unconsciousness, that, you know,

7:33

that's reversible at the end of

7:35

surgery. Now, in the last 20 years,

7:38

you know, anesthesia has gotten a

7:40

lot safer. We've started... innovating

7:42

things like nerve blocks, for example.

7:44

So now we have a little bit more room

7:46

to think about, you know, how much do

7:49

I want to sedate this patient? What kind

7:51

of experience do I want to provide?

7:53

And that's where things start to

7:55

get a little bit interesting. So

7:57

before we get into the research, can you...

7:59

So tell us a little bit about

8:02

how psychedelics work in the

8:04

brain and how they can be used

8:06

as a therapeutic intervention. Sure,

8:08

so this is a very hot topic

8:10

right now. And you know, when we talk

8:12

about psychedelics, what are we

8:15

talking about? There's the classic

8:17

psychedelics, LSD, syllacide. The classics,

8:19

the greatest hits. And then

8:22

there are other drugs that

8:24

are, I would say, psychedelic

8:27

adjacent, that a lot of

8:29

people will identify psychedelic-like properties

8:32

in these drugs. Drugs like

8:34

MDMA, which is nearing approval,

8:36

potentially, for PTSD, ketedomy. Assisted

8:39

therapy. Yes, MDMA assisted therapy, which

8:41

we're going to return to that point,

8:43

I hope. So, and these drugs

8:45

are not, you know, they don't have

8:48

the same perceptual. effect, but they

8:50

clearly are, you know, they

8:52

are acutely psychoactive in a

8:54

profound way that is very

8:56

memorable and unmistakable. And what

8:58

ties all of these together

9:00

and what has, you know,

9:02

led to this explosion of

9:04

research and excitement is

9:06

that when you provide a space

9:08

for people to have a powerful

9:10

psychoactive drug in a

9:13

safe setting and just let them,

9:15

you know, let their mind wander.

9:17

Things come out. Things that, you know,

9:19

if you have PTSD, if you have

9:21

painful memories, if there are things that

9:24

you haven't been able to resolve in

9:26

your life, what people talk about is

9:28

getting a new perspective. You

9:30

know, whether it be like, what is

9:32

going on in my body? Where is

9:35

this pain coming from? Or, you know,

9:37

who is this person who's, you know,

9:39

always depressed and, you know, pessimistic, like,

9:41

all, you know, this perspective shift is

9:44

something that people across these

9:46

drug classes. will talk about

9:48

and to me that's

9:50

what defines this broad

9:52

class. They're acutely psychoactive,

9:54

powerfully so. Their effects are

9:57

rapid, that perspective shift

9:59

or how However you want to

10:01

call it, it's rapid. Change in

10:03

a perception box. You can put

10:05

it that way as well. And

10:07

finally, the effects are durable. This

10:10

is very different from modern mental

10:12

health care. You don't need to

10:14

take these drugs every day. You

10:16

have, long after the ketamine or

10:18

the MDMA or the sulcybin, has

10:20

cleared your bloodstream, you are still

10:22

feeling those positive effects. This is

10:25

a sea change in. in how

10:27

therapy is delivered. And I want

10:29

to emphasize again, it is far

10:31

more complex than just giving someone

10:33

a drug, putting them in a

10:35

room, you know, while they, you

10:38

know, have and have their experience.

10:40

So it's the synergistic effect between

10:42

the actual, you know, physical effects

10:44

of the drug in the brains

10:46

and this psychological effects or impact.

10:48

I'm going to challenge that. I

10:50

think that's actually one of the

10:53

biggest debates right now. And it

10:55

has implications. Is it the drug?

10:57

or the trip that's responsible for

10:59

these therapeutic benefits. Right, like if

11:01

you get the same benefits without...

11:03

Zooming, A and B, empirically, experimentally,

11:05

you can separate those two. That's

11:08

exactly it, right? That's why there's

11:10

the debate, is right now all

11:12

we're looking at is correlation. And

11:14

so tell us more about this

11:16

debate. It boils down to this,

11:18

as you can think of, you

11:21

know, the complexity of psychotherapy, you

11:23

can simplify into three basic stages.

11:25

There's preparation. which involves setting expectations,

11:27

building rapport. There's the drug experience

11:29

itself, possibly eight-hour extravaganza sometimes. 24

11:31

hours. Or 48, it depends, you

11:33

know, the doses, everything. And then

11:36

there's the integration, making sense of

11:38

what happens and trying to incorporate

11:40

those changes into your life. Which

11:42

can take weeks, right? And in

11:44

trials, that's how long it takes,

11:46

that you have weeks of after

11:49

therapy. So, you know, the inclination,

11:51

you know, based on decades of

11:53

experience in, you know, pharma, is

11:55

well, it's got to be that

11:57

little crystalline entity at the... in

11:59

the middle of all of this

12:01

that's driving these effects. But in

12:04

reality, as you pointed out, you

12:06

cannot possibly attribute to one factor

12:08

the therapeutic change unless you can

12:10

independently manipulate them. And this is

12:12

where the science comes in. I'm

12:14

going to put in a brief

12:16

plug for why any of this

12:19

matters. There are people who believe,

12:21

not without cause, that... It's enough

12:23

that it works. Widely, wide, get

12:25

so bent out of shape about

12:27

how it works, it's just enough

12:29

that it does work. And I

12:32

would answer to that is, you

12:34

know, one thing that anesthesia has

12:36

brought me in contact with is

12:38

some of the most advanced medicine

12:40

on earth. And when I see,

12:42

you know, one of the most

12:44

magical moments in residency, and I

12:47

don't need to gross you without

12:49

but watching a transplanted heart get

12:51

put into someone's chest, vibrulate and

12:53

then... convert to sinus rhythm. It's

12:55

like watching birth, like, or the

12:57

earth being born, or a total

13:00

eclipse. It was just all-inspiring. How

13:02

did we get from someone living

13:04

for 50 hours in the 60s

13:06

after a hard transplant to let,

13:08

you know, 80% at five years?

13:10

This is amazing. It's by understanding

13:12

the risk and... understanding the mechanism.

13:15

Mechanism, I mean science, this is

13:17

how science works. And so that

13:19

to me is the question, if

13:21

a therapy is truly potent, by

13:23

definition it carries risk, right? And

13:25

when you think about the early

13:27

days of chemotherapy, chemotherapy in 1975

13:30

was almost a death sentence in

13:32

itself. Thirty years later you have

13:34

the first rationally designed Kainase Inhibitor.

13:36

That blew my mind in 1999.

13:38

Guevak. cured leukemia and you know

13:40

what again that's you take something

13:43

that has it's a powerful chemotherapy

13:45

you know with powerful and crude

13:47

and we learn something and we

13:49

learn something and we learn something

13:51

and we learn something highly effective

13:53

in targeting. I'm not sure that

13:55

CNS, you know, that psychedelics are

13:58

going to go that way, but

14:00

there's a pretty strong track record

14:02

in every other field of medicine

14:04

for this approach. There are also

14:06

strong motives in the industry to

14:08

pursue that, because that's what the

14:10

entire medical system is based on.

14:13

You give one little therapeutic intervention

14:15

that the FDA proves that you

14:17

can then, you know, sell to

14:19

everyone that works. But in this

14:21

case, because this is the most

14:23

complex, you're talking to the most

14:26

complex piece of active matter in

14:28

the known universe. And I seriously

14:30

doubt, having studied my entire life,

14:32

that any one drug will be

14:34

a magic bullet that cures whatever

14:36

existential problems that brain or that

14:38

mine has. I'm going to turn

14:41

that on its head in that

14:43

I completely agree with you, but

14:45

how do you, without demonstrating the

14:47

centrality of like... My overall overwhelming

14:49

sense from all the work I've

14:51

done is that we need to

14:54

center the experience. My biggest question

14:56

is whether it's the molecule itself

14:58

or you need the psychological experience.

15:00

And can you isolate the psychological

15:02

experience so they don't have to

15:04

even take the drug? Are there

15:06

other ways to get to that

15:09

transformative experience? Yeah. That's what we're

15:11

trying to develop is that psychedelics

15:13

pose really fundamental challenges for, you

15:15

know, randomized control trials. Let's start

15:17

with that for a second. Because

15:19

you know you're on the drug

15:21

once you're on it. And so

15:24

why would that be a complication?

15:26

So it introduces all kinds of

15:28

biases in that, you know, the

15:30

randomized placebo-controlled trial was designed for

15:32

antibiotics and blood pressure medication. But

15:34

the power of not knowing whether

15:37

you're on the drug or not

15:39

is really to get around the

15:41

placebo effect thing is if there's

15:43

a certain amount of impact that

15:45

the drug can have just thinking

15:47

you've taken the drug. that can

15:49

have an effect. Probably not for

15:52

TB, I don't see. There are

15:54

some things where placebo effect, you

15:56

know, we should be so lucky

15:58

to have a cancer. or placebo

16:00

effect, right? You know, people don't

16:02

spontaneously, often, do not often spontaneously remit,

16:04

you know, just on the strength of their

16:07

belief, although, you know, there are all kinds

16:09

of stories. But it's important because,

16:11

you know, think about it from

16:13

a patient's point of view. You

16:15

have read Michael Paulin's book. You

16:17

are fascinated at the potential of

16:19

stilocybin. You have out-competed a thousand

16:22

other applicants to be in the

16:24

study on depression. You have already

16:26

one lottery. Right? Now you go

16:28

into the finale. And you've already

16:30

done two other trials. You've already

16:32

failed to other trials and like,

16:34

I think this is going to

16:36

be it. And so you have

16:38

an expectation. It's, you know, it's

16:40

obvious that if I'm, if I get

16:42

the drug... I'm likely to improve because look

16:45

at what all of these smart people say.

16:47

And now comes the moment, the moment of

16:49

truth. You're in, you know, your boyfriend,

16:51

your girlfriend drives you, you know, maybe

16:53

you fight about it because you've been

16:55

so kind of persistent in your pursuit.

16:57

You go through a lot of trouble

17:00

to get to that room, to that

17:02

therapist room and then you take the

17:04

drug and an hour later is either

17:06

a moment of... confirmation and acceptance

17:08

and being seen and being in an elite

17:10

group of people on earth who have a

17:12

bid in a syllacyban trial or a moment

17:15

of betrayal where why did I spend all

17:17

of this effort to be in the placebo

17:19

group? Because nothing happens to me. Because it's

17:21

obvious. It's to most, I mean, it's such

17:24

an obvious cycle act of effect. So, you

17:26

know, if you just, it's like, it's like winning

17:28

the lottery. What is the effect of winning

17:30

the lottery? And you tell me, does that,

17:32

what does that have to do with depression?

17:34

I guess like winning the lottery could

17:36

be a short-term anti-depressive, but that's

17:39

sort of the heart of it. And

17:41

so because they've been told in the

17:43

red that these are wonderful drugs, they

17:45

were less likely to be depressed afterwards.

17:47

That's what you said. That's what the

17:49

placebo factor is. Exactly. But because they

17:51

know if they're on the placebo or

17:53

not with psychedelics, it's very hard to

17:55

control for that. So do you have

17:57

a way that you're trying to get around this?

18:00

So, again, if that's one of the

18:02

biggest problems facing psychedelic medicine is identifying

18:04

a drug-specific effect, it requires some innovative

18:06

solutions. And I'll want to talk about

18:09

a couple. One is efforts by David

18:11

Olson and Brian Roth, you know, two

18:13

great chemists and many others who are

18:15

re-engineering the molecule itself. They're basically trying

18:18

to take the trip. out of the

18:20

drug. Crystal, I'm thinking that's no fun.

18:22

Where's the fun in that? They want

18:25

to take the fun in that? This

18:27

is the science. That's the, that to

18:29

me, it's crucial, right? Like you have

18:31

to test. How can you not? I

18:34

assume you can do that. Let's just

18:36

say for a minute it's possible. You

18:38

will get some answer there is can

18:41

you just encode resilience, you know, biochemically

18:43

without anybody noticing, right? What about giving

18:45

the psychedelic while somebody's under anesthesia and

18:47

they have no experience? That happens to

18:50

be what we did. So I'm so

18:52

glad you have. So it requires a

18:54

lot of different approaches that this is

18:57

the one we took. Now I'm an

18:59

anesthesiologist and one, you know, it's hard

19:01

to escape the idea that, you know,

19:03

you have all these people that come

19:06

in from all walks of life, many

19:08

with pre-existing depression PTSD. That's usually not

19:10

what we're focused on. We're usually focused

19:12

on getting them through surgery. And we,

19:15

you know, we saw this as an

19:17

opportunity is that patients are put on,

19:19

you know, they're put under general anesthesia

19:22

and while they're anesthetized, like there's, you

19:24

know, there's no there there, they're not

19:26

there for it, right? That's kind of

19:28

the goal. So what if we gave

19:31

a psychedelic class drug like ketamine during

19:33

anesthesia during anesthesia? not using ketamine as

19:35

an anesthetic. We're using drugs like propafal,

19:38

drugs like cepaphoring. These are standard anesthetic

19:40

cocktails. And we're getting everyone to a

19:42

pretty even cruising depth of anesthesia before

19:44

we give them either ketamine or placebo.

19:47

So they're deep. So if you do

19:49

surgical cut, they don't. That's the goal.

19:51

They are there for surgery. Now, part

19:54

of how we were easily able to

19:56

get approval for this is that ketamine

19:58

is an anesthetic adjunct. So we were,

20:00

you know, in patients for whom there's

20:03

what we would call equipoise about, you

20:05

know, ketamine is kind of, you don't

20:07

need to give it. There's nothing in

20:09

the case that screams out this patient

20:12

should definitely get ketamine. We're able to

20:14

do this trial. And we ran it

20:16

like a psychiatry trial. And this is

20:19

with actual psychiatrists. like Laura Hack and

20:21

Alan Shasberg who helped, you know, quite

20:23

a bit on this study, but we

20:25

ran a psychiatry trial in the operating

20:28

room. And they give half a milligram

20:30

per kilogram over 40 minutes to minimize

20:32

the psychoactive effects. In a regular wake

20:35

person there would be strong psychoactive, yes.

20:37

Yes, yes, and that's what we've seen.

20:39

We've done other, worked on a trial

20:41

with no one Williams where we're giving

20:44

ketamine to awake patients. At this dose.

20:46

And patients, well, they'll have what's called,

20:48

you know, they'll dissociate. They'll get into

20:51

a dreamy state, you know, they might

20:53

hallucinate. If you listen to what they

20:55

say, there is a lot of overlap

20:57

with psychedelic-like effects. And let's put that

21:00

on pause for a minute, but that's

21:02

the trip of ketamine that we're actually

21:04

trying to see, like, do you need

21:07

that in order to benefit from ketamine?

21:09

So now you give them this dose,

21:11

which normally in a wakeful person they

21:13

would have a sort of psychedelic effect,

21:16

but they're under anesthesia and you have

21:18

a placebo controlled, meaning you're going to

21:20

give them another substance, that's not, you

21:22

just give them no kidney. We just

21:25

give them normal saline. Okay. It's, you

21:27

know, a fluid with the same volume

21:29

and I guarantee you the patients were

21:32

not aware. Everyone was blinded in the

21:34

study. So they wake up and what's

21:36

the measurement? What do you assess? So

21:38

again, we want to copy what's been

21:41

done before when I reinventing anything. We're

21:43

using a standard scale of depression called

21:45

the Montgomery Asberg Depression Rating Scale. It's

21:48

a clinician rated scale, meaning I, if

21:50

let's say you're my patient, I'll ask

21:52

you questions about, you know, tell me

21:54

about your fatigue levels or you know,

21:57

how is your... appetite and there's kind

21:59

of standard degrees of severity but you're

22:01

expecting there to be an impact right

22:04

away right after the surgery. That's the

22:06

beauty of ketamine. S-S-S-R-I is you give

22:08

a patient and maybe six weeks later

22:10

they say you'll feel something maybe and

22:13

it's very hard to like make the

22:15

connection between the drug and the impact

22:17

but with ketamine they give it in

22:19

the psych ER and it really can

22:22

knock out suicidality. And there's new ones

22:24

to everything but essentially yes. That's the

22:26

design of this. therapy is that it's

22:29

rapid acting antidepressant. So you give them

22:31

this measure of depression right when they

22:33

come out of surgery. You don't know

22:35

who's had it and who has it.

22:38

So we waited a day. There's a

22:40

lot of things that happened right after

22:42

surgery. But again, we're copying other studies

22:45

where you have the peak effect, the

22:47

peak antidepressant effect of ketamine is one

22:49

to three days after infusion. Long after

22:51

the drug is gone, you know, where

22:54

we started this description. And that's where

22:56

we're taking our primary measure. is looking

22:58

at depression scores in the one to

23:01

three days post-infusion, post-surgery. And what you

23:03

found was? Well, all of the patients

23:05

who got ketamine did great. They, you

23:07

know, 50% response, 30% remission from patients,

23:10

many of whom had treatment-resistant depression. So

23:12

what about the other patients? Well, so

23:14

the placebo group also did great. 50%

23:17

response, 30% remission remission remission. So it's

23:19

remarkable. So you think whether or not

23:21

they got the ketamine. Both groups on

23:23

average showed the same degree of improvement.

23:26

You could not separate them. The key

23:28

here is that both were massive, massive

23:30

improvements. And there's a couple fine points

23:32

here because I got a lot of,

23:35

you know, wasn't exactly fan mail about

23:37

the study, but people who looked at

23:39

the study say, are you saying tetamine

23:42

doesn't work? And there are a couple

23:44

points to bring out about this. And

23:46

the first point is, what was the

23:48

patient experience? likes and you'll see how

23:51

this is important in a minute I

23:53

think. And again keep in mind this

23:55

very large placebo effect that we saw

23:58

that we were absolutely not expecting. from

24:00

a patient, let's say you're coming in for

24:02

surgery, for 20 years you've been dealing with

24:04

a lot of trauma, the holdovers from a

24:07

rough childhood, etc. And now you're, you know,

24:09

you go see your surgeon and do you

24:11

think your surgeon is going to ask you

24:14

about your mood? We can venture against

24:16

it, usually not. It's the rare surgeon

24:18

that has time because the priorities, there

24:20

are other priorities. So from your point

24:23

of view, you're getting something in your

24:25

email saying we care about your mental

24:27

health and recovery after surgery. you know,

24:29

would you be willing to fill out the

24:31

survey and talk to us? That's our first

24:34

contact with the patient a few weeks before

24:36

surgery. And then you come in, you get

24:38

a consent. It's about an hour long where

24:40

you hear all about the study. Kenamine,

24:42

we think it's an antidepressant

24:44

in other circumstances. We're wondering

24:47

whether this has therapeutic value

24:49

during surgery. Now you come in for

24:51

a two-hour interview with, you know, four of

24:53

us, a nurse, myself. a research coordinator. Who

24:55

always interviewed? Justice, part of the work of

24:58

the study. Yes, we want to know everything,

25:00

you know, and from a patient. So you're

25:02

sort of priming, first of all, they're

25:04

getting more attention, you're talking about their

25:06

mood, you're giving, and you're priming them

25:08

to this drug might really help your depression.

25:10

Exactly, and there have been studies of

25:13

depression during surgery before, and I don't

25:15

think they went all out all out like

25:17

this. We were looking for a particular type

25:19

of patient, type of patient, I was so

25:21

happy to get. each one of them, each

25:23

of these 40, that you know, we really,

25:25

we learned a lot about all of them.

25:27

And so two hours where, you

25:29

know, we heard about their trauma,

25:31

their mental health history, their

25:34

physical, you know, their physical history,

25:36

and then, you know, the morning

25:38

of surgery, I, again, I wanted

25:41

to make sure things go out

25:43

without a hitch. In many cases,

25:45

I held their hands as

25:47

they went off to sleep, right? I

25:49

mean, stop there for a second.

25:52

Why was I so blithely

25:54

unaware of the possibility that

25:56

we might induce this massive

25:59

placebo effect? It's because think the

26:01

broader context is surgical anesthesia. Surgery and

26:03

anesthesia are associated with the higher risk

26:05

of heart attack, stroke, cognitive dysfunction, kidney

26:07

injury, lung injury. Actually, all of our

26:09

literature points to all these things getting

26:11

worse after surgery. Nice. That and putting

26:13

people at risk for opioid use disorder.

26:15

So that's what I came in with.

26:17

All right. I was not thinking that

26:20

placebo would be a problem or that

26:22

the study would even be about placebo.

26:24

It was a big surprise. Well, this

26:26

is my question. I mean, what is

26:28

the takeaway here? Is the takeaway that

26:30

for the effects of ketamine, you don't

26:32

need the psychedelic effect of ketamine for

26:34

there to be an improvement? The takeaway

26:36

is this. It's in the placebo effect.

26:38

We can't say much about ketamine in

26:41

this trial, but what I think we

26:43

can say something about is full of

26:45

the trials going on in the psychedelic

26:47

space. Again, I painted that picture for

26:49

you of winning the clinical trial lottery,

26:51

right, and going through that process and

26:53

all the confirmation bias that might go

26:55

along with it, there are a lot

26:57

of non-drug factors there. So inadvertently, just

26:59

the structure of this trial with preparation,

27:02

a big central event, surgery and anesthesia.

27:04

And then, you know, close follow-up in

27:06

the aftermath, we had, you know, we

27:08

had replicated a lot of the key

27:10

elements of most psychedelic studies and driven

27:12

a placebo effect that is enormous. In

27:14

some ways, this is really good news.

27:16

I mean, first of all, well, where

27:18

is this published, this paper? Nature Mental

27:20

Health. Okay. So, I think everyone should

27:23

take a look at the paper, but

27:25

it's a warning to say, look, look,

27:27

we really need to structure these psychedelic

27:29

studies, these psychedelic studies in a different.

27:31

Like for instance... Your mind can't change

27:33

your body. Yes. So we don't need

27:35

the drugs. We need something. These patients

27:37

went through something. I think that's a

27:39

key part of this. An experience though.

27:41

It was an experience. Yeah, but they

27:44

need this belief. If they don't have

27:46

this belief, so you have to tell

27:48

them that... This thing is magical, whether

27:50

it's a ceremony or dance or beauty

27:52

or molecule. But it's got to be,

27:54

you can't just tell them, you need

27:56

good placebo. We had really good placebo.

27:58

We had the best placebo. Tell me,

28:00

what about the, does the believe that

28:02

the patient, because you must have asked

28:04

the patient, did you think you got

28:07

it or did you think you were

28:09

in the placebo? How does that affect?

28:11

So, you know, they said we weren't

28:13

expecting to come up. So we didn't

28:15

ask people until the very end of

28:17

the study, which group did you think

28:19

you were in? I will say this

28:21

is like one of the only, maybe

28:23

the only, truly blinded study of a

28:25

psychedelic class drug, so that was a

28:28

small victory. But when we asked them

28:30

what they thought they got, so nobody

28:32

knew, first of all, but what in

28:34

talking to them, they're, you know, in

28:36

my conversations with these patients, if they

28:38

got better, they attributed it to the

28:40

ketamine group, because I feel better. which

28:42

suggests that they had some prior belief,

28:44

right? If you wouldn't say that you

28:46

got ketamine unless you believe the ketamine

28:49

is therapeutic. Surely there must have been

28:51

some people who believe it, or maybe

28:53

not, they will believe they were on

28:55

the placebo. And those are the ones,

28:57

yeah, because they didn't get better. They

28:59

didn't get better. And they're like, well,

29:01

I must have been in the placebo

29:03

group. So what that shows, if anything,

29:05

is that we did a job unwittingly

29:07

or not, a good job of instillingling

29:10

a sense of hope. that this has

29:12

the potential for therapeutic benefit. And I

29:14

think that's how you conclude in the

29:16

last paragraph of the paper. This is

29:18

called convention. Is it the short name

29:20

of business hope? Yes. So there is

29:22

a dangerous side to it, not dangerous,

29:24

but we can draw some of the

29:26

wrong conclusions from this work. One is

29:28

that, you know, the convention, placebo is

29:31

an old, an old word, and it

29:33

literally means like, I please. To please.

29:35

Right. One of the kind of awkward

29:37

things is if someone gets better after

29:39

getting placebo and then you tell them

29:41

they got placebo, it's more than a

29:43

little awkward. They're like, well, all that

29:45

stuff I said, well, the throes of

29:47

placebo like was that all like it

29:49

wasn't real right and so it's very

29:52

you know it's it people need to

29:54

feel seen need to feel heard and

29:56

you know, that that idea that placebo

29:58

is just something that you trick children

30:00

with, right? We have to dispense with

30:02

that idea. I think we need to

30:04

harness the placebo. I've always said it's

30:06

harness the placebo effect and use it

30:08

in medicine. Yes, exploit the placebo effect.

30:10

Well, and good doctors do it. Yes.

30:12

Real and in psychical therapy. That's why

30:15

you have Dr. Bowers, I said. Well,

30:17

because if I believe you just like

30:19

a shaman, if I believe you or

30:21

the shaman, then I'm more likely. That's

30:23

true. That has to be part of

30:25

it and there has to be a

30:27

strong experience at the center. I had

30:29

a bar mitzvah when I was 13.

30:31

My father said, today, my son, you're

30:33

a man. And I can tell you,

30:36

my voice did not drop, but I

30:38

felt different. People looked at me different.

30:40

They treated me differently differently. And that's

30:42

right. I mean, and how does that

30:44

happen? It's not a person in isolation.

30:46

It's certainly not a drug effect. It's

30:48

a door that you walk through. that

30:50

is held up by, you know, the

30:52

collective understanding of the community that surrounds

30:54

it. And that is a very devilishly

30:57

hard thing to study with, you know,

30:59

conventional scientific methods. A lot of it

31:01

is the power of suggestion, right? If

31:03

they come in and they're depressed and,

31:05

you know, they're low, I'm never going

31:07

to meet anybody, you know, you give

31:09

them the sort of hope, and they

31:11

believe you because you have all these

31:13

credentials and stuff, like rather than me

31:15

just giving my friends, you know, you

31:18

know, they take your... I really feel

31:20

like you're going to meet someone. I

31:22

really have, you know, I trust that.

31:24

And then they start to believe it

31:26

because someone in a sort of authority

31:28

position gives them that hope. It's not

31:30

about the SSRI, they're taking, but studies

31:32

do show in conjunction, you know, you

31:34

get some powerful effects from the SSRI,

31:36

some from therapy, when they work together,

31:39

you get the synergistic effect. But I

31:41

want to just talk about, because I

31:43

know there's other research you do in

31:45

terms of dreams you do in terms

31:47

of, So going with

31:49

this theme of

31:51

experience, in this study

31:53

that we're just

31:55

wrapping up, the experience,

31:57

they all went

31:59

through something. It's not

32:02

the experience on

32:04

drug, but it's the

32:06

larger experience of

32:08

being in the study

32:10

and going through

32:12

a door, right? Having

32:14

surgery and coming through the other

32:17

side. Was there any

32:19

therapy afterwards? No, like

32:21

every other catamines study, including

32:23

no therapy. And how long did

32:25

you? How long did you?

32:27

Two weeks. And so you

32:29

didn't talk to these people still? Not

32:31

formally. I mean, I kept up with some

32:33

of them and some of the stories,

32:35

I'd love to share some of them. It

32:37

really may be a question whether I

32:39

should be in science or not, when I

32:41

couldn't tell like, is this woman in

32:43

the ketamine group? Because how do you get

32:45

that kind of transformation without something to

32:47

account for it? Of course, she's in the

32:49

placebo group. So

32:52

there's another way to look at

32:54

this. said, coming back to this

32:56

theme of preparation and

32:58

the drug, the day of the dosing, the

33:00

drug and the trip and then integration and

33:02

really focusing on the drug and the trip, which

33:05

you can either take the trip out of the

33:07

drug and we've now talked about a couple

33:09

of ways to do that. What if you could

33:11

take the drug out of the trip? In

33:14

other words, recreate a psychedelic -like

33:16

experience without reference to a

33:18

psychedelic drug itself. That would

33:20

be a pretty interesting way

33:22

to test this idea of

33:24

how special is the serotonin

33:26

to a receptor, right?

33:29

And there's just some very

33:31

exciting research. But now we're talking about

33:33

how do you create hallucinations

33:35

without the psychedelic. So wouldn't

33:37

it be an interesting test if

33:40

we could induce a psychedelic -like

33:42

state without a psychedelic and get

33:44

some of the same physiology, descriptions

33:47

of experience and therapeutic effects? Would

33:49

that maybe turn on its head

33:51

the idea that there's a powder

33:53

at the center of all of

33:55

these therapeutic effects? And that's almost

33:58

by accident what about.

34:01

we've, what we've stumbled upon, working with

34:03

anesthesia and dreams. And I have a

34:05

colleague, Harrison Chow, he's a, I was

34:07

going to say an artist, he's an

34:10

anesthesiologist, but he's, you know, this is

34:12

the art of medicine. He's spent many

34:14

years in private practice, you know, minor

34:16

procedures. Patients would come in for, you

34:19

know, hernias or, you know, doscopies, minor,

34:21

minor stuff, and he would, you know,

34:23

he would try and make the experience

34:25

as pleasant as pleasant as possible. So

34:28

he would do this thing where he

34:30

would watch the EEG monitor and look

34:32

for what he thought was dreaming and

34:34

then patients would wake up and say

34:37

I had the best dream. I had

34:39

the best sleep I've ever had. But

34:41

as you emerge, you know, one of

34:43

the things that you can notice if

34:46

you really pay close attention to the

34:48

EEG, right? This is brain state monitoring.

34:50

So you're watching them as they calm

34:52

out of anesthesia and the wave starts

34:55

beating up and they're getting higher frequency.

34:57

you know, my chair put him together

34:59

with me because he knew I was

35:01

like a psychanot drug nerd into non-ordinary

35:04

states of consciousness and if you shouldn't

35:06

talk to each other and like maybe

35:08

figure something out. It was a great,

35:10

great partnership. Harrison is really like into

35:13

the idea of making anesthesia more pleasant.

35:15

I'm, you know, a little bit more

35:17

scientific and I was very skeptical at

35:19

first. So we agreed. We're going to

35:22

get a portable EEG. a sideline, the

35:24

same, you know, a kind of couple

35:26

leads. We have a team, you know,

35:28

includes a psychiatrist. We are going to

35:31

do, you know, interviews, diagnostic interviews, and

35:33

we're going to follow these patients. I

35:35

want to know is what you're saying.

35:37

Are you bullshitting me? Or is it

35:40

real? Is there something there? And not

35:42

long after we had our first case.

35:44

And this is a case of a

35:46

woman. This is published in 2022. Where

35:49

this woman, she... She had been attacked

35:51

at close quarters by a relative with

35:53

a knife, horrifying. As you might imagine,

35:55

she had nightmares, right? She went to

35:58

the emergency room and they said, go

36:00

to Stanford. get your hand fix and

36:02

you know in the intervening time. The

36:04

hand got injured. Yeah, exactly. So the

36:07

surgery was too helpful. The surgery was

36:09

for her hand and she you

36:11

know in the intervening two weeks

36:13

she's basically a non-functional human right

36:16

she's hypervigil and she's you know

36:18

having difficulty. So due to the

36:21

time frame we call it acute

36:23

stress disorder but this is somebody

36:25

who would more likely than not we

36:28

would be worried she would go on

36:30

to develop PTSD. So she's in the

36:32

pre-op area, right? She's just there for

36:34

her hands. You know, and Harrison finds

36:36

her, again, still, you know, it's all

36:38

she can talk about, and she's really,

36:41

you know, hard to reach. And they,

36:43

again, talking about like innovations and

36:45

anesthesia, they put her arm to

36:47

sleep. She gets a nerve box and

36:49

Harrison does a dream thing. Wait, so

36:52

is her arm anesthetized? Yeah, her arm

36:54

is anesthetized. So she doesn't need to

36:56

be so deeply anesthetized that she can't

36:59

feel it. When you say the stream thing,

37:01

it's just that you're controlling the amount

37:03

of profafal. And watching the EEG and

37:05

getting her into the sort of sweet

37:07

spot where he knows that the dreams

37:09

occur. Yeah. How long is this state of

37:12

dreaming in this patient? About 10 minutes.

37:14

Well, very agree. relatively brief,

37:16

but there's a lifetime in 10 minutes.

37:18

Yeah. So what she, you know, what

37:21

she says immediately upon waking is the

37:23

nightmare. It was it was there

37:25

again. I had the nightmare again and

37:27

it was looping just like it always

37:30

does, but instead of rocketing her into

37:32

consciousness, right, which what a

37:34

nightmare is, by virtue of this anesthetic

37:36

suppression. She stays in that state and

37:38

she actually in her dream moves past

37:40

the attack. She in her dream goes

37:42

to the emergency room, goes to the

37:44

operating room. She's back home running errands

37:46

with their hand. All in this 10

37:48

minutes. A lifetime in 10 minutes. Just

37:50

to go back for a second, just

37:52

because in terms of therapy, you know,

37:55

often like I'm working with traumatic with

37:57

patients who've had trauma and the idea

37:59

is to help. them, you know, work through

38:01

the emotions is to sit with

38:03

the thing that makes them anxious

38:05

or uncomfortable long enough. Yeah, exposure

38:07

long enough to get through it

38:09

and resolve it and then move

38:11

on. But often people, as soon

38:13

as they get, you know, the

38:15

cortisol comes or whatever, they want

38:17

to avoid it and they never

38:19

get through that. So maybe that

38:21

being in the stream state allowed

38:23

her to get past the anxiety

38:25

part of it enough so that

38:27

her brain was able to kind

38:29

of process it. We're thinking along

38:31

similar lines. So first of all,

38:34

we followed her for a day,

38:36

a week, a month, a year,

38:38

and what is still remarkable to

38:40

me is she's able to just

38:42

talk about this attack. No nightmares,

38:44

like, you know, she's basically, she's

38:46

functional. She's a functional person who

38:48

has recovered from trauma. You're seeing

38:50

you two 10-minute dream. Well, we've

38:52

done it now about 600 times.

38:54

And patients, so we've been, this

38:56

is clinical care, this is gentle

38:58

clinical care that now we've added,

39:00

you know, an observational study on

39:02

top of just seeing what happens

39:04

when we do this at scale.

39:06

And, you know, the technique isn't

39:08

perfect. We have, you know, somewhere

39:10

between 60 and 85% hit rate

39:12

for getting patients to have these

39:14

vivid dreams. And I can tell

39:16

you, you know, the things that

39:18

patients say upon awakening, you know,

39:20

this was more real than real.

39:22

I expected to be somewhere else.

39:24

Patients are having a very powerful

39:26

experience. It's more than just regular

39:28

dreaming. And do you find that

39:30

they're less anxious after or less?

39:32

Well, so what we actually, the

39:34

real clincher, or what was so

39:36

surprising is, you know, just by

39:38

chance, two patients that came through

39:40

Stanford operating rooms had bona fide

39:42

PTSD in both cases. Coincidentally, it

39:44

was the loss of a child,

39:46

an adult child, either due to

39:49

drug overdose or suicide. You know,

39:51

again, a horrible thing to live

39:53

with for years. And, you know,

39:55

as you can imagine, nightmares about

39:57

trying to save your child, like

39:59

it's really, we didn't know this

40:01

before they went to sleep. This

40:03

all came up in the immediate

40:05

aftermath, where putting... them into these

40:07

states for 10 to 15 minutes,

40:09

they emerge, one of our patients,

40:11

Mayor, and she's, there's a story

40:13

on the Stanford Med School blog

40:15

now, detailing her experience. She dreamt,

40:17

you know, she re-experienced the birth

40:19

of her son, instead of being

40:21

a traumatic birth, it was, it

40:23

was joyful. She was reunited with

40:25

her, with her son and with

40:27

her family, and they were, and

40:29

listening, we have a video also

40:31

on our family, on our family,

40:33

on our family, on our family,

40:35

on our family, on our, on

40:37

our, on our, on our, on

40:39

our... on my lab website, it

40:41

still gives me chills actually to

40:43

even listen to that she says

40:45

thank you for this, you know,

40:47

being able to have that experience.

40:49

And, you know, Mary, you know,

40:51

and Edie and the patients who

40:53

tell us these things have. invigorated

40:55

a small army of people in

40:57

the operating rooms who are now

40:59

like trying you know they want

41:01

to do this. But then it's

41:04

transformative after the fact then they're

41:06

less upset about these traumatic events.

41:08

She's had nightmares her entire life

41:10

and especially after this you know

41:12

this traumatic event and now you

41:14

know what she's telling us a

41:16

year later is that she has

41:18

not had nightmares. I mean what

41:20

this tells me is that you

41:22

know However you get to these

41:24

transformative experiences, whether you take MDMA

41:26

and that allows you to sit

41:28

with the trauma and work through

41:30

it and process it, in this

41:32

sort of drug-induced dream state, that

41:34

allows you to sit with the

41:36

trauma and process it, or the

41:38

psychedelic experiences. And even these intense

41:40

placebo experiences, there is something about

41:42

the psychological effect of sitting with

41:44

the anxiety and working through it.

41:46

And however you can, psychedelics are

41:48

a way to get there, but

41:50

they're not the only way. This

41:52

woman, it sounds wonderful, but it's

41:54

just one other three, you said

41:56

there's several hundred, or it's most

41:58

patients? So most patients, so again,

42:00

this is, we're doing this on

42:02

the background of providing clinical care.

42:04

So these patients... So they all

42:06

come in again for other types

42:08

of surgery. Yeah, they're coming in

42:10

for, you know, thyroid surgeries, plastic

42:12

surgery, you know. But they know,

42:14

they always get football before. But

42:16

the goal is always the same,

42:19

is during emergence, we are targeting

42:21

a state, right? We've had patients

42:23

report this with CIVA foreign, with

42:25

propafal, and Remy fentanyl. Again, this

42:27

hits at the point, it's not

42:29

the drug. So that being said,

42:31

in terms of what we're starting

42:33

to learn from the science and

42:35

from these experiments, is that it's

42:37

not necessarily the chemical molecule itself

42:39

that's having the impact on transforming

42:41

these. patients or people who have

42:43

anxiety and mood disorders. It's the

42:45

psychological experience that seems to be

42:47

the most impactful therapeutic here. And

42:49

trying to understand what are the

42:51

bounds, like how do we define

42:53

that, what are the characteristics that

42:55

need to be present in order

42:57

for it to be transformative? At

42:59

the end of every episode, we

43:01

ask a perception box question, and

43:03

our question today is... What aspects

43:05

of yourself are you now grateful

43:07

for that in the past you

43:09

struggled with or hated? I can

43:11

give, I can speak up. I

43:13

used to start as a little

43:15

child and I went to logotherapy

43:17

for like six weeks and I

43:19

was, you know, I just couldn't

43:21

do it particularly when people were

43:23

looking at me like in this

43:25

scenario. But then I sort of

43:27

challenged myself and did this on

43:29

purpose to get into a situation

43:31

where I needed to control my

43:34

language. And I don't know because

43:36

it was when I was nine

43:38

and 10 and 11, I did

43:40

the sort of mindfulness training, etc.

43:42

Then I managed to overcome that

43:44

and use that as a way

43:46

to learn how to give talks

43:48

and how to convince people. So

43:50

I think this has turned to

43:52

benefit. Might even overcompensated younger brothers,

43:54

10 years younger, but so for

43:56

10 years, I was an only

43:58

child. And I developed for, you

44:00

know, I was very, you know,

44:02

in my own world. And for

44:04

many years, I would kind of

44:06

hold ideas and I would not,

44:08

I didn't want to share them

44:10

until they were perfect and they

44:12

would marinate and stew and one

44:14

day, you know, during my PhD,

44:16

you know, during my PhD, something

44:18

clicked being in a, in a

44:20

lab and my mentor, Pablo Castillo

44:22

really nailed this for me. in

44:24

the arguing, the joy of, you

44:26

know, exposing yourself and your ideas.

44:28

It takes a certain amount of

44:30

courage or a jump. It's, you

44:32

know, these are things like my

44:34

ideas, my dreams, like these are

44:36

things that are really deeply special

44:38

to me that, you know, I

44:40

want to hold on to and

44:42

I want to kind of protect,

44:44

but what I found very quickly

44:46

is that by exposing them and

44:48

talking, you know, and really just...

44:51

pairing them apart in a way.

44:53

Some of them didn't survive. But,

44:55

you know, we have the saying

44:57

in my lab now that, you

44:59

know, if an idea can survive

45:01

this room, my office, after talking

45:03

about it for three hours, there

45:05

might be something there. That's the

45:07

power of discourse, which I think

45:09

we're losing now. A lot of

45:11

people are, you know, trigger warnings

45:13

and safe spaces and whatever, but

45:15

to actually be able to have,

45:17

you know... arguments and discourse. So

45:19

it's deeply enjoyable. I engage in

45:21

this community of people. Yeah, absolutely.

45:23

And it shifts your perspective and

45:25

your ideas. So my, I think,

45:27

I don't know if it's more

45:29

superficial or not, but the first

45:31

thing that came to my mind

45:33

is, you know, I used to,

45:35

you know, being an academic and

45:37

being a woman, I, a lot

45:39

of the time, and this was

45:41

like, you know, in the 90s

45:43

and the early 2000s, just wasn't

45:45

taken seriously if I was... too

45:47

feminine like wearing makeup dress whatever

45:49

so I used to like dislike

45:51

my femininity and dress down and

45:53

not wear makeup and wear baggy

45:55

clothes and whatever to be taken

45:57

seriously at places like Oxford and

45:59

Harvard and all the, and there

46:01

was this unconscious bias and stereotype,

46:03

and if I would walk in

46:06

to give like a lecture or

46:08

a keynote, immediately, expectations were lower,

46:10

if I was more, let's say,

46:12

feminized. And so I really tried to like

46:14

hide that aspect of myself, and

46:16

then I, as time went on, and I got

46:18

more confident, and I know what I know,

46:20

and I know the science, and I had

46:23

confidence, I didn't have to like

46:25

pretend anymore that I wasn't. feminine

46:27

and I could wear makeup and dress

46:29

the way I want and whatever and

46:32

still be taken seriously and actually take

46:34

advantage of those lower expectations because if

46:36

I come in like oh you're the keynote and

46:38

then they have lower experience rather someone

46:40

like crystal because with the German acts

46:42

whatever they're expecting to say something very

46:44

intelligent but he doesn't and it's a

46:47

big disappointment whereas I have this great

46:49

advantage where I they have lower expectations

46:51

and then I can you know show

46:53

what I know so I'm very grateful

46:55

now for that, but that was a part

46:57

of myself that I used to kind

46:59

of try to downplay. So yeah, that's

47:01

mine. It's a bit superficial, but I

47:04

think still meaningful. That runs pretty

47:06

deep. Yeah. Well, I want to thank

47:08

you, Forrest, for being here with us

47:10

today. Thank you. Thanks for having me.

47:12

This is a lot of fun. Fascinating

47:15

conversation. So if you'd like to

47:17

learn more about your own perception

47:19

box, spend some time this week

47:21

answering the same perception box questions

47:23

that we asked your guest, and

47:26

check out other questions on the

47:28

website at unlikely collaborators.com. You could

47:30

also subscribe to our YouTube channel

47:32

and watch the show or listen

47:34

wherever you get your podcast. This

47:37

has been Science of Perception Box

47:39

created by Unlikely collaborators in partnership

47:41

with pod people. I'm Dr. Heather

47:43

Berlin. Thank you very much.