0:06

You're listening to WellNow, Slate's podcast

0:08

on health and wellness. I'm Maya

0:10

Feller. And I'm Kavita Patel. Psychedelics

0:13

like psilocybin, LSD, and MDMA seem

0:15

to be showing up everywhere. I

0:18

recently attended a wellness and longevity

0:20

event where microdosing of psilocybin and

0:22

other mood-altering substances were touted as,

0:25

quote, the medicine we all need,

0:27

end quote. Peer-reviewed studies

0:29

show promising results in treating

0:31

various mental health conditions such

0:33

as depression, post-traumatic stress disorder,

0:35

anxiety, addiction, and end-of-life

0:38

distress. But despite

0:40

this great progress and great awareness,

0:42

there has still been reluctance especially

0:45

from regulators, including most recently the

0:47

Food and Drug Administration's Advisory Committee,

0:49

which voted to recommend against approval

0:51

of one of the first psychedelics

0:54

that would be available in the

0:56

market. A key FDA advisory

0:58

committee today rejected the use of

1:00

a psychedelic drug to help patients

1:02

struggling with post-traumatic stress disorder, questioning

1:04

the trials and its effectiveness. The

1:07

FDA must now decide whether it

1:09

will follow suit and reject the

1:11

use of what's known as MDMA.

1:13

Some patients and researchers had long

1:15

hoped the government would approve it.

1:18

The manufacturer, Lyco, sought a

1:20

recommendation for its drug, mitomythemine,

1:22

otherwise known as MDMA, specifically

1:25

for the treatment of post-traumatic stress

1:27

disorder. In what

1:30

was considered a blow to many advocates

1:32

and patients, it was actually compelling, Maya,

1:34

to hear from so many

1:36

veterans and other patients during the open

1:38

comment period for this advisory committee meeting

1:41

where they were just begging and discussing

1:43

the fact that for the first time

1:45

there was something that was actually possible

1:48

that could get them through what felt

1:50

like a very dark tunnel, especially for

1:52

persons with post-traumatic stress disorder. While

1:55

we're still waiting for the FDA to make a final decision,

1:57

it seems very unlikely

1:59

that would move forward with approval

2:02

when an advisory committee has

2:04

given a recommendation to not

2:06

move forward. So, Maya,

2:08

this brings up a very important point

2:10

around psychedelics in general and just part

2:12

of what I think has become a

2:14

very, I would say, conventional

2:16

discussion. It feels like I'm

2:19

constantly just hearing or even

2:21

talking to people about the role that

2:23

psychedelics could play as part of treatment

2:25

for some of the disorders that I

2:27

discussed. Maya, what exposure

2:30

have you had in your professional

2:32

or personal life to psychedelics? Yeah,

2:34

Kavita, I think it's such an

2:36

interesting conversation and just as you

2:38

said, it's become so conventional. I'm

2:40

hearing it more and more from

2:43

patients that are coming in saying, oh,

2:45

do you know someone who uses

2:48

psychedelics as a part of their

2:50

treatment modality? Actually trying to get

2:52

referrals to providers because whatever

2:56

conventional pharmacology they're taking

2:59

isn't eliciting the desired response

3:01

that they're looking for. I

3:03

know some of the patients that we

3:06

work with have had long and very

3:08

ongoing chronic depression that has a real

3:10

impact on their quality of life and

3:13

it impacts how they interact

3:15

with their families, get to work, all

3:17

sorts of areas that someone who's not

3:20

dealing with that may not think about.

3:24

People are seeking and they're searching and

3:26

the truth is I

3:28

have very few people

3:30

that I would trust to

3:33

refer my patients to for

3:36

this psychedelic assisted treatment because

3:38

A, it is so novel

3:41

and I'm careful to

3:43

say this. I know that there are

3:45

times where there are people who say

3:47

that they know what they're doing and

3:49

they don't have the experience. My

3:52

estimation shouldn't really be working

3:56

with the psychedelics and patients.

3:58

It's hard to say, well, we're not doing this. where should people turn

4:01

because so many folks are suffering? And

4:03

I'm hopeful that in the coming decade

4:05

and with research that's going on that

4:07

we'll have a credible place to send

4:10

people who are interested

4:12

in psychedelic assisted treatments. So

4:15

Kavita, I'm interested, what about

4:17

you? What are you seeing in your

4:19

kind of work area? So I

4:22

will say that I will probably be

4:24

labeled, you recall a former guest we

4:26

had, Dave Asprey, where I

4:28

think he succinctly pointed out just how

4:30

much kind of conventional or Western doctors

4:32

have failed patients. I would probably say

4:35

that a day we're sitting here listening

4:37

to us talk, you would probably say

4:39

the exact same thing around this topic.

4:42

And I wouldn't challenge him that much. I

4:44

do not find many of my colleagues

4:47

who often come forward and

4:49

say, here is a really

4:52

important role for psychedelics in this

4:54

treatment, anxiety, post-traumatic stress. I worked

4:56

in a VA where we were

4:58

actually one of the clinical sites,

5:00

not for the drug I mentioned,

5:02

but for just exploring the role

5:04

of psilocybin and other kind of

5:06

psychedelics in post-traumatic stress disorder. And

5:08

I vividly recall Maya that the

5:10

team that was working on it,

5:12

like it was always just kind of back of the

5:14

break room kind of jokes, but people would say like,

5:17

oh, those are the mushroom people. Like, oh, those are

5:19

the folks tripping on acid that

5:22

are trying to get the vets to do it. And

5:24

there was part of me at the same time, like

5:26

I would laugh and then I'd walk away and I'd

5:29

be in the emergency room and we would see what

5:31

was very clearly like

5:33

a textbook of post-traumatic

5:35

stress disorder that was poorly treated. And

5:38

at the time I was working in the

5:40

VA, it was Operation Iraqi Freedom Veterans that

5:42

we were seeing. We had still had a

5:44

stable kind of cohort of Vietnam veterans, but

5:46

sadly we just got used to seeing so many

5:49

Vietnam vets, but it became a very different proposition

5:51

when I would see 26 year olds showing up

5:53

and had such severe PTSD, their

5:56

lives were torn apart, which is what I think

5:58

some of my colleagues saw decades earlier. after

6:00

the Vietnam War. So on one

6:02

hand, we would make fun of the teams that

6:04

were doing the very research that I think I

6:06

have personally, I've been trying to learn a lot

6:08

about. I think that's why you and I wanted

6:11

to do this topic for this podcast. But

6:13

at the same time, there's an incredible

6:15

stigma and it's treated as a fringe

6:18

science. I will say that I

6:20

think you and I have spoken about like you

6:22

and I read a lot or we try to

6:24

read a lot. And I think that there

6:26

have now been prominent, including

6:28

someone that we're going to talk to in

6:30

this podcast, but prominent psychiatrists

6:33

and psychologists that have really

6:36

brought the science together, talked

6:38

about like where there is a role

6:40

for psychedelics. And I don't

6:42

think that anybody could

6:44

have an episode without mentioning the body

6:47

keeps the score. And Dr. Bessel van

6:49

der Kolk, I'm going to not

6:52

pronounce his name exactly accurately, but I

6:54

will just say that the book, The

6:56

Body Keeps the Score or an abridged

6:58

version of that is probably a good

7:00

staple. And I've encouraged my own colleagues

7:02

to read it, those who have not,

7:04

because it does explore some of these

7:06

topics. And I think it's

7:08

an important discussion. Maya, I think you've

7:10

read or at least we've talked about

7:12

this book. Have you found anything else

7:14

to be helpful in just educating yourself

7:16

or educating your colleagues on this topic?

7:19

Well, you know, there's some really interesting

7:21

providers that I work with and

7:23

someone that we're going to have on the show

7:25

in the future. So I won't say his name

7:27

today, but he has for

7:29

a very long time worked

7:32

with ketamine specifically around PTSD.

7:34

And he also has been

7:36

talking about this for decades.

7:38

And what I have learned

7:40

from my colleagues who actually do prescribe

7:42

and work with psychedelics as a part

7:44

of their treatment modality is that it

7:47

is completely individualized. And

7:50

we'll talk about this, but Kavita, one

7:52

of my questions as well. So if

7:54

we're getting such great outcomes, how

7:56

do we make this actually accessible to a

7:58

wide variety of people? of people and

8:02

in a really safe way. So

8:06

that comes to mind for me so

8:08

often is like, yeah, what does

8:10

the future look like? Especially because just as you

8:13

said, we're seeing people younger and younger. And I

8:15

have folks who come through the practice as young

8:17

as 15 who are experiencing

8:20

these unstable symptoms and they're in

8:22

and out of psychiatric emergency departments.

8:25

I mean, 15 is young, right?

8:28

So I have hope for the future.

8:32

Yeah, I'm looking forward to our episode today.

8:34

And I feel like

8:36

this is going to scratch the surface and

8:38

will be the beginning. But I really want

8:41

to learn more because I think that there

8:43

are some blind spots just as you said,

8:45

Kavita, where in the past I may have

8:48

not taken it as seriously as I could

8:50

have. Yeah, that's why we're really excited to

8:52

bring in Dr. Dave Rabin to speak

8:54

to us not just about this topic,

8:57

but I think about his lifetime of

8:59

training and pursuing what I

9:01

would say has been like, you know, an

9:03

incredible challenge for any of us

9:05

dealing with these diagnoses. So Dr.

9:07

Dave Rabin has an MD and

9:09

PhD from the University of Pittsburgh

9:11

Medical Center completed his medical training

9:13

in psychiatry and is a board

9:15

certified psychiatrist. We really look forward

9:18

to speaking with him after this short break. Hey,

9:32

well, now listeners, if

9:34

you're enjoying the show

9:36

and want to

9:43

hear more, subscribe

9:50

to our feed. New episodes come

9:52

out every Wednesday morning. While

9:54

you're there, check out our other episodes too,

9:57

like last week's about how mold affects

9:59

the air. we breathe with

10:01

indoor air specialist, Michael Rubino. Check

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that works for you at

11:10

onepeloton.com/financing. Welcome

11:15

back. You're listening to Well Now. I'm

11:17

Maya Feller. And I'm Kavita Patel. When

11:20

we decided to tackle the important topic

11:22

of psychedelics and healthcare, there were only

11:24

a handful of names that

11:26

we wanted to speak with. They all happened

11:28

to start with Dave and ended with Rabin.

11:30

So here we're very excited. Dr. Dave Rabin,

11:32

Dave, thank you so much for joining us.

11:35

Thanks so much for having me. It's a pleasure to be here with you both. All

11:38

right, great. So Dave, we start with a

11:40

question standard to all our guests and

11:42

you can take it in whatever context you like.

11:44

How do you define wellness? That's

11:50

a great question. I mean, I think I

11:52

define wellness as balance more

11:55

than anything, or just kind

11:57

of like equanimity, but ease. Things

12:01

are just flowing easily.

12:03

There's evenness and balance.

12:06

I was influenced by a

12:08

lot of ancient health

12:11

literature from Eastern and tribal practices that talk

12:13

a lot about health as balance in

12:16

their practices and then also my study

12:18

of the autonomic nervous system. That's where

12:20

that comes from. I

12:22

have to say that I love that

12:25

you started off with ease and

12:27

balance and then you brought in ancient

12:30

wisdom and the autonomic nervous system.

12:32

We're not even five minutes in

12:34

and I'm like, all right, I'm

12:36

going wherever you're going. I'm with you. Awesome.

12:42

Dave, tell us a little bit about

12:44

your journey into psychiatry and neuroscience. What

12:46

really sparked your interest in this field?

12:49

Well, I think it started pretty young for

12:51

me. I was, I don't know, maybe between

12:53

the ages of four and seven and

12:56

like many young boys and young children, I

12:58

had very vivid dreams at night and they

13:01

weren't always nightmares or bad dreams. Sometimes

13:03

they were great dreams or they were

13:05

just regular old interactions with people

13:08

like my siblings, but I did

13:10

not realize that they were

13:12

not dreams because I found myself referencing them

13:15

in conversation with my brother or a

13:17

friend who was present in the dream

13:20

for me. I eventually started to

13:22

have more scary dreams and so I went to my

13:24

parents and I said, hey, what's going on when we're

13:26

dreaming like this is getting kind of weird and they're

13:28

like, oh, don't worry about that. It's not

13:30

real. I'm like, well, what does that mean? I'm

13:33

like, you know, they're like, well, you know,

13:35

real is this. Real is like the experience

13:37

that we're having right now. It's

13:40

real. It's our reality. And what

13:42

happens in your dreams is not

13:45

real. And I think what they were really trying

13:47

to say is it can't

13:49

hurt you in the same way

13:51

that things can hurt you like

13:53

a car, right. And your dream is not going to

13:55

hurt you the same way a car hitting you in real life would hurt

13:57

you. And I think that's what they were trying

13:59

to tell me. to make me not afraid of

14:01

sleep, like most parents tell their kids. But

14:03

as I kept having these dreams, I

14:06

didn't have them very often, but you

14:08

know, as you keep having

14:10

them and they seem so real, as real

14:12

as waking life, you

14:15

know, I think I did something that a lot of people don't do,

14:17

which is I started to ask the question of what

14:19

does the word real really mean? And

14:23

maybe the adults don't know,

14:25

right? Maybe they don't realize

14:27

that what's going on in here is actually

14:30

real and that we just

14:32

need to look at it through a different lens.

14:34

And so from a very, very young age, I

14:36

started reading like sci-fi and becoming

14:38

fascinated by consciousness and the mind and and

14:40

sort of the way we think and make

14:42

meaning of the world. And then of course,

14:44

how that ultimately impacts the way we deal

14:46

with stress and the way we grow from

14:48

challenges and how we deal with illness. And

14:51

and so when psychedelic medicine came along,

14:53

I was studying neuroscience.

14:56

I mean, psychedelic medicine has been around for a long time, but it

14:59

was not yet mainstream at this point.

15:01

This is like 2012. And

15:04

so I was studying neuroscience and psychiatry

15:07

and mental health, but I

15:09

really wasn't convinced that I was going to

15:11

focus my life on treating mental illness and

15:13

focusing on mental illnesses

15:15

as my path and clinical psychiatry is

15:18

my path. And so I

15:20

had a good friend who was

15:22

in my medical training program who sent me 10

15:26

of the latest, most exciting

15:28

publications in the psychedelic space

15:30

associated with psychiatry. And

15:32

I stayed up all night reading these papers and

15:34

I was blown away by the quality of the

15:37

science and the way that

15:39

these results were really starting

15:41

to look like paradigm shifting results for

15:43

the field of psychiatry. And like

15:46

we could actually start to get to the root cause

15:48

of what's going on underneath some of the layers of

15:50

mental illness. And that was more

15:52

exciting to me than anything because I always love

15:55

to solve hard problems and do

15:57

like puzzles and challenges and things

15:59

like that. So this was like the greatest challenge

16:01

ever was to really figure out how

16:04

are psychedelics working to get

16:06

these dramatic benefits in mental illness.

16:08

And if we can figure it out, then

16:11

maybe we can replicate it with other non-psychadelic

16:13

tools like technology. And so that's kind of

16:15

where I saw my path and I went

16:17

full force into psychiatry at that time and

16:20

studying consciousness and psychedelics and

16:22

mental health. It seems like

16:24

you were entering psychiatry. I'm not gonna

16:27

make any assumptions about age and time,

16:30

but it feels like you were kind of really

16:32

present and studying during that time when

16:35

I don't think you and I could

16:37

have found, I think maybe DSM-IV, like

16:39

one of the textbooks of psychiatry and

16:42

really have found a role at that time

16:44

for psychedelic assisted therapy. The trials were ongoing

16:46

or peer review studies had just come out.

16:50

And yet here you are, like I think we're

16:52

now at a moment where what

16:54

might've felt very unconventional, Dave now feels

16:56

like I've got people who don't even

16:58

know I'm a doctor, talking to me

17:01

about kind of the role of potentially

17:03

like psilocybin or have you been seen like

17:05

kind of where there could be some

17:08

potential for MDMA and PTSD.

17:11

So you really were not just at that

17:13

inflection point, but you've continued to be, I

17:15

think, an advocate for thinking about the role

17:18

of psychedelic assisted therapy. Can

17:20

you just describe like how

17:22

psychedelics are being used in therapy? And

17:25

then who are like the patients for which this

17:27

is, in your mind, like

17:29

when you think about this, like who should

17:31

we be bringing this forward to? Who are

17:33

the ideal patients for this and the benefits

17:35

of it? So I think, you

17:38

know, just to start off, the only legal

17:40

psychedelic medicine that is

17:42

available today is ketamine. Right. All

17:45

other psychedelic medicines are

17:47

not actually federally legal to be

17:49

delivered by a hospital

17:52

or clinician. So

17:54

that means that whether it's generally speaking,

17:56

even in legal states, cannabis is federally

17:58

illegal. MDMA, psilocybin

18:00

mushrooms, LSD, ayahuasca, almost

18:03

all of it is federally illegal

18:05

and can't be administered to you

18:07

by a licensed clinician. So

18:10

that's a really important distinguishing

18:12

factor that most people overlook because a

18:15

licensed clinician has a board and has

18:17

overseeing bodies that regulate how they practice.

18:20

Even though people still mess up and

18:22

make mistakes, there are

18:24

consequences. In

18:27

decriminalized states or in states where this is

18:29

not federally legal, which is for all of

18:31

those drugs I just mentioned, cannabis,

18:33

MDMA, psilocybin, other plant medicines,

18:35

LSD, etc. Whenever

18:37

you're getting those administered, in general, you're getting

18:40

them from an unlicensed clinician or

18:42

somebody who's not a clinician at all but claims to

18:44

be or is not a shaman but claims to be.

18:47

Who knows how much experience this person has? It's

18:50

really hard to tell. The

18:54

lack of effective legislation and

18:56

legalization around the way that we

18:58

use and think about these medicines

19:00

creates effectively like an abstinence-only education

19:02

situation we have for sex but

19:04

for drugs. Now people

19:07

are accidentally misusing

19:09

and abusing drugs because they're

19:11

seeking healing because the

19:13

current system that is ... I

19:16

still don't think that there's any psychedelic

19:18

medicine in the DSM to date. I

19:21

still don't think it's there. I think that what

19:23

is there is ketamine for maybe depression. I

19:27

don't even know if that made it in yet. The

19:30

field is way behind. A lot of

19:33

people are seeking psychedelic drugs because of

19:35

the hope and promise that's being talked

19:37

about, but then there isn't an actual

19:39

legal framework that's safe for people to

19:42

achieve them. Safety is

19:44

the most important single criteria for

19:46

being able to get healing

19:48

outcomes from psychedelic medicine.

19:51

That's what the whole therapy is really all about. Ketamine

19:54

is the only legal medicine, but the way they

19:57

generally work is they amplify ...

20:00

Awareness so where is

20:02

this thing like right now you're we're all aware

20:04

of each other right cuz we're having a conversation

20:06

requires a lot of attention but

20:08

in general are awareness has so much

20:10

more to it like everything that's going

20:13

on happening in our bodies and around

20:15

our bodies wow we're just

20:17

thinking about this conversation which

20:19

is a million billion things right

20:21

and are hearts pumping in our lungs are

20:23

breathing in our you know skin is doing

20:25

its thing and ignoring the feeling of the

20:27

clothes in our bodies right and all these

20:29

different things are happening we're digesting our food

20:33

and so we can at any time be

20:36

made aware of that information that's stored

20:38

in what Freud and Carl Jung called

20:40

like the subconscious or the unconscious content

20:42

of our lives which is guess what

20:44

what comes up in dreams the very

20:47

first psychedelic state that any of us

20:49

have going full circle. I

20:51

have to pause for a second because

20:54

as you were speaking I was having

20:56

an internal discussion like wow well this

20:58

is mind-blowing because you're

21:01

right for so many of us

21:03

in our lives we actually put

21:05

our dreams aside and separate ourselves

21:07

from that dream state when

21:09

I feel like what I'm hearing

21:11

from you is that there's a lot of value in that

21:14

and I know just from a nutrition perspective we actually talk

21:16

about sleep as being a rejuvenating moment for folks and like

21:18

something that's going on in our lives. I think that's really

21:20

important for folks and like something that none of us get

21:22

enough of but it seems Dave like dreams

21:25

and that state is also quite

21:27

powerful. Yeah, absolutely. That's where all of

21:29

our memory. Recon consolidation happens in dreams.

21:31

which is typically what we call REM

21:33

sleep so it's where the most important

21:35

short term memories that we form during

21:37

that past whatever amount of time when

21:40

we were awake gets transition

21:42

and filtered and transitioned and story and

21:44

long term memory and organized

21:46

properly right? All

21:49

the things that it was related to and not be connected

21:51

to things it wasn't related to so that's

21:53

what's called memory consolidation and that's what happens when

21:55

we dream and in REM sleep and

21:57

that is where we get all of our like emotional.

22:00

and cognitive mental rest and recovery. And then

22:02

deep sleep is where we get all of

22:05

our physical rest and recovery throughout

22:07

the day. So that's why it's so important

22:09

why we don't function properly when we don't

22:11

get good sleep. So

22:15

Dave, I know that you're engaged in

22:17

quite a bit of research and study.

22:19

And right now, I'd love

22:22

to hear you tell our

22:24

listeners a little bit about

22:26

the epigenetic study that you're

22:28

conducting with MAPS, the Multidisciplinary

22:30

Association for Psychedelic Studies and

22:32

the nonprofit Modern Spirit. Tell

22:35

us a little bit about that research and what

22:38

some of the expected outcomes are

22:40

going to be. So that study is actually

22:42

published, which is really exciting. We

22:45

published it in February of last year. And

22:48

the origins of this work were to try to

22:50

understand, as I mentioned earlier, if we're

22:53

seeing, I don't know how much of your

22:55

audience is familiar with the results from some

22:57

of the psychedelic clinical trials. But what's so

22:59

amazing about these results is that one

23:02

to three doses of the medicine, in

23:05

the case of ketamine, it's more, because ketamine is

23:07

shorter acting, but maybe it's 12 doses. But point

23:09

is one to 12 doses of psychedelic

23:11

medicine spread out over 12 to

23:13

20 weeks can

23:15

take somebody with an over 50%

23:18

likelihood of success,

23:20

which is way better than

23:22

what we're seeing with antidepressants and other treatments.

23:24

I would say for MDMA, it seems like 78

23:26

to 88% ketamine, something like 60 to 80%

23:28

meaning of people

23:32

who have severe mental illness

23:34

coming in and having, to

23:36

answer your question earlier, who's

23:38

a good candidate, people with PTSD and

23:40

depression in particular, are top candidates.

23:43

Other mental illnesses, we have to do

23:45

a little bit of therapy work in

23:48

preparation. Schizophrenia, bipolar, absolutely not. Personality disorder,

23:50

absolutely not. Active drug

23:52

abusing people, absolutely not.

23:55

But everyone else, for the most

23:57

part, depression and PTSD are

23:59

all great. candidates. And

24:01

so the way that the medicine

24:04

works is that it helps them to

24:07

feel safe enough in their bodies

24:11

to be able to observe

24:13

the trauma that has been

24:15

stored in their bodies. Trauma

24:17

being the

24:20

way our body responds to

24:23

very intense, meaningful,

24:27

challenging experiences that we interpreted at whatever

24:29

time it was that they happened as

24:31

threat and that we didn't have support

24:34

for after. Dave, that makes

24:36

me think about the current

24:39

pharmacology that is being prescribed.

24:41

What is that pharmacology getting

24:45

versus missing? Meaning

24:47

how is it actually impacting the person

24:49

and where is there space that it's

24:52

not impacting? I

24:54

love this question. So the way that the

24:56

current drugs work is that

24:58

they're stabilizer drugs. So think about the

25:00

model that we use for an ER

25:03

for treating acute illness. We're applying to

25:05

chronic mental illness, but we don't have

25:08

an actual solution to the problem. So

25:11

in the case of most psychiatric drugs,

25:13

they either like amphetamines, Adderall, Ritalin, well

25:15

butrin, they turn you up. They

25:18

help increase your focus so you can

25:20

focus away from distressing thoughts. Then

25:23

there's all the sedative hypnotic

25:25

drugs, the benzodiazepines, the barbiturates,

25:30

the ambient, the other things that are

25:32

very sedating. Those all

25:35

numb you to emotion. Generally

25:38

speaking, they just decrease awareness. They're dulling.

25:40

They work kind of like alcohol. So

25:43

they just decrease your overall sensation on the whole

25:45

and then you're less sensitive to things in your

25:48

environment, which is why a lot of people who

25:50

take those drugs often resemble people who are drunk

25:53

in behavior and functionality. So then

25:56

there's the middle class, which is

25:58

like SSRI antidepressants. So

26:00

these medications work by shrinking

26:03

the emotional window. So

26:05

the serotonin receptor is really, there's many

26:07

of them, but the one we're talking

26:10

about here is called

26:12

the 5-HT2A receptor in particular,

26:14

and it's responsible for, it

26:16

seems, meaning-making in

26:18

a lot of ways. And that it

26:21

requires burst activation to make meaning. That

26:24

could be positive meaning and awareness of

26:26

positive things that you make meaning from, or

26:28

it could be negative. The point is it

26:30

requires a burst of activation at that receptor

26:32

site to have those meaning-shifting, meaning-making effects. When

26:35

you overwhelm the receptors

26:37

and you saturate them,

26:40

what happens is the receptors get overstimulated.

26:43

And this is what happens with SSRI antidepressants.

26:45

This is how they work, is they block

26:47

the reuptake of serotonin. So here's the cell

26:49

that's releasing serotonin, and it's like, ploop, ploop,

26:51

ploop, pumping out serotonin, right? And then it's

26:53

pulling the serotonin back in every time it

26:55

pumps it out. But now you

26:57

take an SSRI, it binds this thing, and it says, you're not

26:59

going to pull it back in, you're just going to keep putting

27:01

it out. So now there's an SSRI on

27:03

board, and you got

27:06

this neuron pumping out serotonin, and

27:08

then you have the receiving neuron. And the receiving

27:10

neuron is sucking that serotonin up. And

27:12

then now there's a flood of serotonin

27:14

in here. So the receptors that are

27:17

receiving serotonin on the receiving neuron say,

27:20

I'm overwhelmed, overstimulated, I

27:22

need to go hide. And so

27:24

they literally withdraw back and decrease

27:26

their sensitivity serotonin. At

27:29

the receptor site, that seems

27:31

to be really, really important for

27:34

meaning making. What

27:36

is the single most common side effect of

27:38

people who take SSRIs long term? Dullness,

27:42

numbness, apathy, loss

27:45

of meaning in their lives. So

27:47

there's really like a neurochemical relationship

27:49

between how these medicines work and

27:51

what they actually

27:53

do to us, which is so interesting.

27:56

The point is they're all stabilizing medications.

27:58

They work really, really well. well in the short

28:01

term, they work

28:03

really, really poorly long

28:05

term, because it would be like

28:07

you coming into the ER with a broken leg

28:09

and the doctor's like, oh, you're in a lot of pain.

28:12

You have a broken leg. Take these pain pills, right?

28:14

And then he's like, well, we can't fix that right now because

28:16

you don't have enough money and there's not enough time or doctor's

28:18

on, so why don't you just go home and hang

28:21

out with that broken leg and this bottle of pain pills and

28:23

then months go by and years go by and

28:26

you still have a broken leg that

28:28

never quite healed properly or works

28:30

right now. And it

28:32

has all these scars and you're

28:34

addicted to pain pills. So

28:36

that's basically what we're currently doing with

28:38

the way we prescribe for chronic use

28:41

every major anti mental health medication when

28:43

especially when we don't include therapy, which

28:45

is required. So psychedelic medicines like break

28:48

that trend by creating

28:50

these massive burst activation

28:52

experiences at the serotonin

28:54

receptor that activate that

28:56

receptor for an extended period of time, but

28:58

just for just for like six hours. And

29:01

in that six hour period, it seems

29:03

we're dramatically increasing the learning capacity of

29:05

the brain, the neuroplasticity of the brain

29:07

to form new connections around the

29:09

way we actually want to think about ourselves

29:11

from a perspective of safety. And

29:14

so the safety is actually like

29:16

reprogramming the fear learning that's accelerated

29:18

by the molecular action of the

29:20

psychedelic drug. And that's why its

29:22

mechanism is so freaking cool and

29:25

unique and just game changing for

29:27

the field. I mean, it

29:29

sounds like we need a

29:31

lot more discussions like this,

29:34

a lot more research. But in

29:43

the meantime, we're going to take a break here. And

29:45

when we come back, we'll hear more

29:47

from Dr. Dave Rabin on psychedelics in

29:50

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31:14

You're listening to WellNOW from Sleep. I'm

31:16

Maya Feller. And I'm Kavita Patel. We're

31:19

continuing our conversation with Dr. Dave Raven.

31:22

Dave, I love how much kind

31:24

of vivid imagery you offer when we're trying

31:26

to describe. I don't think as someone who's

31:28

taken a peer-reviewed study and

31:31

offered like such depth and hope to it. But

31:33

let's kind of take that through to what I

31:36

would suggest is a setback in

31:38

the field. And you can disagree with me,

31:40

but there's a recent advisory committee meeting that

31:42

you well are aware of for the Food

31:44

and Drug Administration. And we don't know what the

31:46

final action of the FDA is at the time

31:49

of this recording, but it seems like it would

31:51

be difficult for the

31:53

FDA to go against the recommendation of

31:55

the advisory committee, which was

31:57

against a bit of a double negative. the

32:00

approval of the therapeutic for PTSD,

32:03

mitomyphetamine or MDMA. And

32:06

I heard, as probably you did,

32:09

some of the incredible public comment

32:11

during the open comment period, veterans,

32:13

veterans' rights groups, patient

32:16

advocacy groups, providers, physicians,

32:18

all kind of groups who basically

32:21

said a little bit of kind of

32:23

a piece of what you just

32:25

described in your recent study and

32:27

what kind of promise that

32:29

MDMA could hold, particularly for patients

32:31

with post-traumatic stress disorder. First,

32:34

Dave, just your reactions to what

32:36

you kind of heard in

32:38

that advisory committee meeting, and

32:41

then tell us about what the future

32:43

holds. If you're somebody with a diagnosis

32:45

of PTSD, you were really hoping and

32:47

thinking about this therapeutic, the studies that

32:49

were obtained to get to that point,

32:52

and kind of what I describe as a setback,

32:55

but what do you do? If you're one of

32:57

the patients that have

32:59

this diagnosis? Yeah,

33:02

it's a really heartbreaking and

33:05

challenging situation for the field, more

33:08

so for patients and veterans than

33:10

for anyone, because

33:13

there was so much hope that

33:16

was around these treatments working,

33:18

because from the data

33:21

that I was describing to you and the data from

33:23

my colleagues' studies and the data from our studies, we're

33:26

seeing that

33:29

MDMA-assisted therapy is

33:31

effectively, if the published

33:34

results are true and

33:36

consistent with what was actually discovered in

33:38

the study, which is these, which

33:42

we don't have any reason to believe that's not the case

33:44

right now, which is that MDMA-assisted

33:48

therapy appears to be through

33:52

amplifying the molecular pathways of safety

33:55

in the brain, helping to not

33:58

only clinically, induce

34:00

symptom remission that is dramatic

34:04

in people in the short term, but also

34:06

it perpetuates into the long term for at

34:08

least a year after the treatment has been

34:10

stopped with just three doses and

34:12

42 hours of psychotherapy over 12 weeks.

34:16

And that that experience

34:19

patients are having is not just

34:21

shifting how they score on depression

34:23

and PTSD scales that are clinically

34:25

validated. But it's also in

34:28

our study, the epigenetic study has

34:30

also shown that the

34:33

more people get better from MDMA

34:35

assisted therapy, the

34:38

more repair

34:40

of their cortisol receptor functioning

34:42

they have. And

34:44

that cortisol receptor in particular is

34:47

implicated in trauma, and

34:49

that it gets damaged epigenetically

34:51

by trauma. So this

34:53

is like really needs to be taken into

34:56

consideration given that over 70% of veterans

34:59

who are currently getting treatment with the

35:01

treatments available, the gold standard treatments are

35:04

not getting better long term. And

35:06

they have twice as high a suicide rate as

35:08

everybody else. So that's the playing field that we're

35:10

in right now. And so I

35:12

think it goes without saying that the FDA

35:15

advisory committee that was composed of

35:17

only one person from the FDA,

35:19

one or two people from pharma, and

35:21

then a bunch of academic clinicians who

35:24

I don't think are particularly familiar with

35:26

the background and what the history

35:28

of MDMA with the FDA is, maybe they

35:31

are. But they focused

35:33

on it was very surprising that they

35:35

gave that opinion that they gave and it was

35:37

an opinion, right? It's an

35:39

opinion. It's like you asking me my opinion.

35:42

And I don't I don't think I

35:44

think that was what it even

35:46

if it is correct, even if they're right, it

35:49

was the opinion and the vote

35:52

were issued without taking into account the sensitivity

35:54

of the matter. Right. And

35:56

I think that this is really hurtful to a

35:58

lot of people. patients are

36:00

really struggling right now and they're losing faith in the

36:02

medical system and that's the last thing we want them to

36:04

do. Like medical system is our

36:07

last bastion of hope where

36:09

people will still believe because so many

36:11

of us care that we're actually trying

36:13

to help and heal them

36:15

in the world, right? And without that

36:18

structure, a lot of

36:20

our society doesn't really have a

36:22

backbone to stand on. So

36:24

that trust is really important. And I don't

36:26

think they were really considering that when they

36:28

were releasing the outcomes of their boat. So

36:32

Dave, where's the hesitancy? Because

36:34

I'm sitting here listening, both Kavita

36:36

and I work with patients

36:39

and we know the mental health

36:41

crisis that's happening in this country

36:43

across all ages, right? There's no

36:45

contesting it, right? So

36:48

where's the hesitancy in

36:51

adopting this

36:53

as part of the treatment protocol

36:55

that could have really

36:57

beneficial outcomes? And

37:00

as you said, really kind of reinstall

37:02

faith A in the medical system, but

37:04

also help people to simply live better

37:06

lives. It's a

37:08

good question. I don't

37:11

think we know the entire

37:13

answer yet in all of its

37:15

detail, but what the committee has

37:17

said is that there

37:20

are concerns that have not been

37:22

fully disclosed to the public yet

37:25

about the

37:27

level of

37:29

rigor in

37:31

terms of certain ways that the clinical trial

37:34

was conducted. And

37:36

this is a 38 year

37:38

project that MAPS and Rick Doblin have

37:40

been working on, MAPS, now LICOES, but

37:44

they've been working on this for 38 years. So

37:46

they put a lot of time and thought into

37:48

this. And I'm sure that they made mistakes because

37:50

everyone makes mistakes doing anything, let alone running FDA

37:53

trials, which are incredibly challenging. And they did

37:55

it as a nonprofit. So it's daunting task.

37:59

But the committee brought up that there

38:01

were certain things that they believe

38:03

could make it challenging to

38:06

interpret the results. And

38:09

so I think now

38:11

what this is really calling for is a full

38:13

review by the FDA to actually make sure that

38:16

the results are the results. Because

38:19

if the results are the results, as far as I'm

38:21

concerned, it goes without saying, this

38:23

is not an if situation. This

38:26

needs to be a when situation. And

38:28

if more information needs to be put

38:31

forward to determine is this

38:33

actually healing people? Or

38:35

is it hurting people? And if

38:37

it's hurting people, are those risks we can mitigate?

38:40

And if we can't mitigate them, then we need to do another

38:42

trial to show we can. And so

38:44

we have to think about this as a

38:47

when problem. And the FDA

38:49

might say that they think

38:52

that the benefits outweigh the risks after doing a full

38:54

review. And we can only hope. Right? And

38:57

like being said, they often take the advice of the

38:59

advisory committee. So I hope they don't.

39:01

I hope they do their full own

39:03

review and actually look at the results

39:05

and understand the impact this

39:08

has for patients in the community

39:10

and how much it means to the community to

39:12

be able to have tools that are new and

39:14

that work. Our

39:16

SSRIs like Paxil and Zoloft are our

39:18

only two FDA-cleared drugs for PTSD. And

39:21

we've had them for 25 years without a new one. So

39:24

again, I think this is going to

39:26

be a when problem, not an if problem. But we just need

39:29

to focus on educating everybody

39:31

so that people understand what this

39:33

means. And

39:35

the government needs to be educated. People need to

39:37

understand what this really means in

39:40

the community and how these treatments work. And

39:43

they're not like 70s rave party drugs. This

39:46

is medicine. And that's what we're talking about. Dave

40:04

Raben is a psychiatrist who specializes

40:06

in treatment-resistant mental health disorders. Dave,

40:08

thank you so much for joining

40:10

us. It's my pleasure. Thanks

40:13

for having me. That's

40:17

our show this week. Well Now is produced

40:20

by Vic Whitley-Barry with help from Kristi Tyro

40:22

MacEnjola. Ben Richmond is

40:24

Slate's Senior Director of Podcast Operations. Alicia

40:27

Montgomery is Vice President of Audio. We'd

40:30

love to hear from you. Email us

40:32

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Plus. Your contribution makes the

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work at slate.com/Well Now Plus. And

40:51

be sure to tune in next Wednesday as we

40:53

tackle another part of the wellness industry. I'm

40:55

Kavita Patel. And I'm Maya Feller.

40:58

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