0:21

Welcome to the Making Sense podcast. This

0:23

is Sam Harris.

0:25

Today I'm speaking with Jeannie Fontana

0:28

and Robin Carhart-Harris. Jeannie

0:31

is a MD-PhD and

0:33

a leader in the healthcare space. She

0:36

has been instrumental in increasing federal funding

0:38

for ALS research and

0:40

is a founding trustee of the California

0:42

Institute of Regenerative Medicine, where

0:45

she played a pivotal role in creating the world's

0:47

largest stem cell granting agency with

0:50

an $8.5 billion budget. After

0:52

her influence, the agency achieved FDA

0:55

approvals, fast-track designations,

0:57

and launched groundbreaking clinical trials. Additionally,

1:00

it helped create over 55,000 jobs

1:03

in California, 50 new companies,

1:05

and $10 billion in added state revenue.

1:08

And now Jeannie is focused on a

1:11

new initiative,

1:12

which we'll be talking about. It is called

1:14

Treat California,

1:16

T-R-E-A-T, and

1:18

this is a citizen-led ballot initiative

1:21

that will provide $5 billion in funding

1:24

for research and affordable access to mental

1:26

health treatments using psychedelic

1:28

medicines.

1:30

You can get more information at the website treatcalifornia.org,

1:33

but the immediate

1:35

need now is that they have to collect 1

1:38

million signatures from registered California

1:40

voters. So if you are a registered

1:43

voter in California, you can go to treatcalifornia.org

1:47

and download a petition, print it out, and

1:49

sign it. And whether you're a registered California

1:52

voter or not, you can collect signatures

1:54

from California residents. And there's more information

1:57

on the Treat website about how to do that.

1:59

And wherever you live on Earth, you

2:02

can donate to TREAT, because

2:04

gathering one million signatures is actually a very expensive

2:07

thing to do. It usually costs many

2:09

millions of dollars, because it all has to be done

2:12

physically. You can't just sign a petition

2:14

on the website. You'll hear much more

2:16

about the initiative from Jeanne in a few moments, but

2:19

I just wanted to give you the call to action up front. Once

2:21

again, that website is TREAT, T-R-E-A-T,

2:25

California, dot org. Jeanne

2:28

and I are also joined today by Robin Carhart-Harris,

2:31

who founded the Center for Psychedelic Research at

2:33

Imperial College London, the first

2:35

center of its kind, in 2019. Then

2:39

in 2021, Robin became the inaugural Ralph

2:41

Messner Distinguished Professor of Neurology

2:43

and Psychiatry at the University of California,

2:46

San Francisco. He's also been listed by

2:48

Time Magazine as among the 100 next. This

2:51

is a group of emerging leaders from around the world

2:53

who are shaping the future. He holds a

2:55

PhD in psychopharmacology from

2:57

the University of Bristol,

2:59

and he's led neuroimaging studies with LSD,

3:02

psilocybin, MDMA, and DMT,

3:04

as well as several clinical trials

3:06

for psilocybin therapy. The

3:09

topic of discussion today is the TREAT

3:11

initiative in California

3:13

and the growing promise of psychedelics for mental health

3:15

care.

3:16

We cover some of the recent research and

3:18

just generally explore how we

3:20

seem to be at the tipping point here. After

3:23

all the time that was lost when these compounds

3:25

were criminalized, it seems that the

3:28

commitment to research at this point feels

3:30

rather unstoppable.

3:32

And it's certainly no exaggeration to say that

3:34

what happens in California could well

3:37

determine what happens in the United

3:39

States as a whole.

3:41

And now I bring you Jeanne Fontana and

3:44

Robin Carhart-Harris. I

3:47

am here with Jeanne

3:50

Fontana and Robin Carhart-Harris. Jeanne, Robin, thanks for joining

3:52

me on the podcast. Thank you, Sam. Thank

3:56

you, Sam. So what

3:58

we're going to talk about today is the TREAT initiative.

3:59

talk about psychedelics and

4:02

their therapeutic potential

4:04

and the current state of the scientific research,

4:07

but also we're going to talk about this very

4:09

ambitious initiative that, Jeannie,

4:12

you are launching in California. Before

4:15

we start, perhaps each of you can summarize

4:17

your professional background and tell

4:19

me how you came to focus

4:22

on this particular issue. So, let's

4:24

start with you, Jeannie.

4:25

Thanks. Robin

4:28

and I are pointing fingers at each other. You're first.

4:32

Well, I'm trained as an MD-PhD.

4:35

I'm trained as an

4:37

internist and then I have a PhD in

4:39

biochemistry and molecular biophysics.

4:42

I started as a young woman thinking that

4:44

I was going to develop some therapeutic

4:46

that would help treat millions

4:49

of people. So, I've always kind of had this drive

4:51

in me since I was young.

4:54

As I finished all my training, which was long

4:56

and extensive, my mother

4:58

was diagnosed with ALS

5:01

and at the time I

5:04

remembered it was one of those horrible diseases that I read

5:06

in my textbook, but I really did.

5:08

There was not much known about this. This was back in the

5:10

late 1990s. And

5:12

so, I thought with all my

5:14

education and my privilege

5:16

in life that I had an opportunity

5:18

to

5:20

dive into drug discovery

5:22

to help find a therapy.

5:25

Of course, starting off trying to find one for

5:27

my mother,

5:28

but then also getting involved with the ALS community

5:30

and realizing that

5:32

there's such a desperate need here

5:34

for research and patient

5:36

care. So,

5:38

I dove all in

5:41

and I don't know how long, which

5:43

time you want me to spend on this, but

5:46

this experience

5:48

brought me to

5:50

participating in changing federal legislation

5:53

for ALS and that was really empowering for

5:55

me to

5:56

know how to work within the system to change

5:59

what

5:59

laws that impact the lives of tens

6:02

of thousands of ALS patients in

6:04

perpetuity until the law was changed.

6:07

And also going back to the Department of Defense

6:09

and increasing funding for ALS and

6:12

understanding and learning quickly how to work within

6:14

the system

6:15

to increase funding because at the time there was

6:18

next to zero funding from the

6:20

National Institutes of Health, which is where most of

6:22

the funding comes from for basic research.

6:25

So that was interesting.

6:27

And then at the same time human embryonic

6:29

stem cells were just discovered in the late 1990s

6:32

and I happened to be working with a

6:35

very beautiful medical

6:38

research institute in San Diego where there were top

6:40

scientists there.

6:41

One was a leading stem cell scientist and

6:44

brought this to my attention is not to

6:46

replace neurons in a dish but to create

6:48

a disease in a dish because we can't

6:50

study human brain tissue easily. So

6:53

it was very exciting to think

6:55

about having the capability of a

6:57

large scale pharmaceutical companies where we could

6:59

identify molecules,

7:01

a disease of modifying molecules.

7:04

At the same time George Bush

7:05

put a moratorium on the funding of embryonic

7:07

stem cells for political reasons and

7:10

so it was

7:12

one of those aha moments where you say wait

7:14

there's

7:15

some real therapeutic benefits from

7:17

this research and not having any

7:19

funding and watching all of

7:21

this research stopping in essence just

7:24

screeching halt and

7:26

reacting to that.

7:28

Unfortunately there was a force of nature here in California

7:30

from

7:31

Silicon Valley whose son had

7:33

juvenile diabetes and he

7:35

was always looking for a therapeutic cure and had been

7:37

speaking with the scientists at Stanford

7:39

and they were talking about the promise of stem cells

7:41

and recognizing that

7:44

the federal government was limiting the amount of funding on it.

7:46

So there's a pathway in California

7:50

where the citizens can demand that

7:52

the California government actually

7:54

provide services that they want. In

7:56

this case we

7:58

launched a citizen driven balance. initiative

8:00

to create

8:01

the first of its kind funding agency

8:04

for embryonic stem cells.

8:06

And I was on that campaign

8:09

and educating the public about it and educating

8:10

doctors and patients

8:13

and

8:14

participated in, you

8:16

know, editorials

8:17

and things like that. And I honestly did not

8:19

think the bill would pass. We

8:21

were in a bleeding economy

8:23

at the time. And

8:24

when I was lobbying at the Sacramento

8:27

with some of the politicians there, they said, wow, this is,

8:29

yes, it seems to be promising in the time

8:31

it really was in its basic research level.

8:34

But we can't pay our teachers

8:36

in our, our police department and

8:38

our firemen. And why should we

8:40

spend this kind of money on basic research?

8:43

And I didn't have an answer. I agreed

8:45

with them. I said, you know, God, we have to be our teachers

8:48

in our, so, but what I

8:50

learned is

8:51

that in 2004,

8:53

it was the citizens of California that approved

8:56

this citizen driven ballot issue and created

8:58

the first of its kind in the largest in the world,

9:00

a $3 billion funding agency

9:03

focused on stem

9:05

cell research. So

9:07

I was honored by being a board

9:10

member creating this new Institute.

9:12

And we were charged with expediting bench

9:15

to bedside research, which is normally

9:17

takes about 15 years

9:19

to go from the lab to a

9:22

therapy at the bedside.

9:23

And on average in the $2,000 was about $1.5 billion. So we wanted

9:25

to set up a granting agency

9:31

that was improved upon the NIH system.

9:34

And we had people from all over the country

9:36

in the world, actually reviewing the

9:38

different granting agencies. And we

9:40

set up something that I think,

9:42

by all accounts ended up being pretty successful.

9:45

So by the end of the 15 years when the

9:47

money ran out, we had

9:49

two FDA approved therapeutics and

9:51

about nine breakthrough and fast tracks therapeutics.

9:54

And importantly, we had 60 compounds, what

9:56

we say in the pipeline that were deserving of further

9:59

funding. So the same force of nature

10:01

went back to the voters of California

10:04

during the height of the pandemic and qualified for the

10:06

ballot. And the voters

10:08

of California approved an additional $5.5 billion.

10:13

So in

10:15

addition to bringing therapies to the

10:17

patients, CIRM is also

10:20

credited with bringing about 55,000 additional

10:24

jobs to California and 50

10:26

companies born out of this.

10:29

An additional about $10 billion in

10:31

revenue to the state. So I

10:33

recognize now that we created

10:37

and built what is now the regenerative

10:39

medicine

10:40

infrastructure.

10:41

And it took me a while to really

10:43

appreciate how amazing that was.

10:47

And I'm so proud of

10:50

participating in something where we actually

10:52

delivered

10:53

on our promise, which

10:56

was expediting bench to bedside research

10:58

and bringing therapies to patients and

11:00

creating

11:01

a whole new industry of which now

11:03

we'll combine it with gene editing

11:06

and other future breakthroughs that we

11:08

have in medicine that we combined and we will actually

11:11

cure

11:12

some incurable diseases now.

11:14

Nice. So this is a long introduction.

11:16

I've stopped here. Yeah, that's great. Everything

11:19

I can keep on going. Yeah, well, we'll pick up the trail

11:21

there talking about that initiative

11:23

pathway. But let's bring in Robin. Robin,

11:26

how did you come to study the brain

11:29

and the nervous system and what have you focused

11:32

on and how did you come to focus on psychedelics?

11:35

Yeah, so I was

11:37

a

11:38

curious teenager. I could say

11:40

I had some experiences and

11:42

I felt a

11:44

gravitational pull to psychology.

11:47

I did a

11:48

degree in psychology

11:50

in my hometown of Bournemouth

11:53

on the south coast of England. And then

11:54

towards the end of that, I

11:57

enrolled to do a master's

11:59

in psychology. analysis. I was

12:01

especially drawn to depth psychology.

12:04

But that said, I was also drawn

12:06

to rigorous

12:09

scientific approaches

12:12

to the mind. Perhaps psychoanalysis

12:16

can be a little weak in that sense.

12:18

But... A few parts of it have

12:20

not aged especially well. But

12:22

maybe some of them have. Maybe some are sometimes

12:25

a little bit underappreciated. But yeah,

12:27

I was drawn to neuroscience and

12:30

I ended up getting

12:32

lucky with an opportunity at the University

12:35

of Bristol to do a

12:37

PhD in psychopharmacology

12:40

focusing on the serotonin system,

12:43

doing some polysomnography,

12:45

so sleep recordings of

12:48

MDMA users and matched

12:51

controls who had their

12:54

serotonin systems stressed with something

12:56

called tryptophan depletion and dietary

12:59

manipulation. But anyway, this was kind

13:01

of my way in. And I did come

13:03

to that unit. It was David Knott's

13:05

unit, Professor David Knott, former

13:08

so-called drug czar in the UK, the chief

13:11

scientific advisor to the UK government on

13:14

drug policy. And I came knocking

13:16

on his door asking to do psychedelic research.

13:19

And he opened it saying, well,

13:21

you can do some serotonin research and we'll

13:23

see how things go. But I

13:26

was especially interested in psychedelics.

13:28

I'd learned of their history

13:31

being used as tools

13:33

to assist psychotherapy.

13:35

And actually often that was a

13:38

kind of depth psychotherapy and

13:40

a similar in a sense, quite similar to

13:43

psychoanalysis or be an accelerated

13:45

version. And that was kind

13:48

of my way in. So on

13:50

completing my PhD, then I had, again,

13:53

a good opportunity, some good fortune

13:56

through a visionary

13:58

philanthropist Amanda Fielding.

13:59

Beckley Foundation to do some

14:02

brain imaging work. That's really what I wanted

14:04

to do. I came to David initially

14:06

wanting to do an LSD fMRI

14:08

study. I had this hypothesis

14:11

that the psychedelic

14:14

state was like a waking dream

14:16

state, a hybrid dream

14:18

sleep waking state. And

14:20

I thought through the lens of fMRI,

14:24

functional brain imaging, I could in

14:26

a sense prove that hypothesis. That was my

14:29

naivety at the time. But that

14:31

was the initial thread that drew me in. And since

14:33

then, I've done a series of brain

14:36

imaging studies with a range of different psychedelic

14:39

drugs, psilocybin, LSD,

14:41

MDMA, DMT. And

14:44

off the back of that, off the back

14:46

of some of the insights that we were getting from the brain

14:49

imaging, I set up

14:52

first a clinical trial with psilocybin

14:54

therapy

14:55

in treatment-resistant depression. And then

14:58

since then, that kind of got a ball

15:01

rolling at a certain time. And I

15:05

guess we're going to go there. But

15:07

yes, a lot of momentum now

15:10

in psychedelic medicine.

15:11

Yeah, well, I want to talk about the state

15:14

of the research and

15:16

how you differentiate the promise

15:18

of the various compounds you mentioned

15:21

and perhaps others. But before

15:23

we go there, let's talk

15:25

about the treat initiative because I want

15:28

people to know about it up

15:30

front here. My wife, Annika,

15:33

is the one who told me about it.

15:35

And she's been involved

15:37

with Eugenie helping it along.

15:40

And she, in preparation for this

15:42

conversation, she has

15:45

let me know that she thinks it's difficult

15:47

to communicate the full vision

15:50

of this initiative. And so I'm wondering,

15:52

Jeanie,

15:53

can you explain what you're hoping

15:55

to accomplish and

15:57

perhaps anticipate any common

15:59

misunderstandings of what

16:02

you're attempting to do.

16:04

I

16:06

laugh because it is

16:08

an enormous project

16:10

with many layers, so it is

16:12

a challenge to try to sum

16:14

it up

16:15

in a few words. But I've been

16:18

practicing this

16:19

quite a bit because I think what

16:21

we have here is an opportunity

16:23

to

16:24

transform the way

16:27

we deliver mental health care

16:29

to

16:30

start in California.

16:33

These medicines are showing great promise

16:36

through clinical trials performed

16:38

from our top academic institutions

16:41

that are nothing short of jaw-dropping

16:45

to me. And as a scientist

16:48

who looks at data,

16:49

it's rare that one comes across

16:52

such promising preliminary data with the

16:55

outcomes of patients

16:57

who otherwise aren't

16:59

treatable.

17:01

So the goal of

17:03

the Treat Institute is

17:06

to bring these medicines to the public

17:08

in a responsible, safe, and ethical

17:11

manner.

17:12

Now in order to do that, there's

17:14

a lot of details

17:16

that need to be addressed.

17:18

But I think we can take the high perspective

17:21

and talk about

17:22

how we have to show these medicines to be safe

17:24

and efficacious, meaning large-scale clinical

17:26

trials,

17:28

and tracking

17:29

safety data, tracking outcome

17:31

data, not just during the clinical

17:33

trial period, but over lengths of time.

17:35

And

17:36

if for your listeners that are aware of

17:39

medical studies, something like the Framingham study

17:41

where we tracked

17:43

through

17:44

generation, the lifetime actually, the

17:46

outcomes of the patients,

17:49

I think it's important to look at the different

17:51

indications that these medicines

17:54

can help with.

17:55

Right now we know that it

17:56

requires a therapist

17:58

in the room, that the

17:59

that seems to be the combination of therapy,

18:02

talk therapy with these

18:04

medicines. And that

18:06

resonates with me as an athlete

18:08

who was taught how to play a sport.

18:11

When you're taught how to do something, you

18:13

can do it better. And I think in our society,

18:15

we're not taught how to manage

18:18

our emotions

18:19

in a healthy way. So I think

18:21

the patients need to be

18:23

prepared and educated with how

18:25

to experience these medicines

18:27

and what

18:28

to importantly do with the

18:30

insights

18:31

and emotions elicited through

18:33

the medicine.

18:34

So integration is a huge component of

18:36

this.

18:37

And then importantly is access. I

18:40

believe strongly that these medicines need to

18:42

be available to all,

18:45

not just the rich right now, and

18:47

not just those that through

18:49

their insurance policies they're able to take

18:52

and others are not. We're

18:54

well aware that the hardest hit

18:56

communities in any society are

18:59

the underserved communities and

19:01

mental health while affecting

19:03

every citizen

19:04

of America right now.

19:06

They're personally with their family members

19:09

or certainly with their friends is

19:11

being touched by this.

19:13

So the tools though that are provided to

19:15

the underserved communities are particularly

19:18

sparse. So

19:20

main impetus of the treat initiative

19:22

is to make sure that these medicines

19:24

and treatments are available to all.

19:26

So I think I'll stop there because I can take

19:28

up all your time here telling you about it so.

19:31

Yeah, well, so I wanna remind

19:33

people at the end of our conversation, but I wanna get

19:35

upfront the specific

19:38

call to action if there is any

19:41

for California residents now

19:44

and what is the actual initiative?

19:46

We are running a campaign

19:48

and it's called the Treat California Campaign

19:51

and the treat stands for Treatments, Research,

19:53

Education, Access and Therapies

19:56

for Mental Health Using Psychedelic Assisted

19:58

Therapies in order to...

19:59

for the ballot, which we're going to begin

20:02

to do in two weeks,

20:04

we need a million signatures

20:07

to sign the petition saying they're interested in

20:09

this to get on the ballot. The signatures

20:11

need to come from registered voters. So

20:14

we appreciate people going to our website

20:16

and signing up so that when we

20:19

get our green light to start collecting

20:21

signatures, we'll be able to reach you and

20:23

have you sign this petition.

20:26

If we don't get the million signatures

20:28

to qualify for the ballot, then this dream

20:31

dies.

20:32

So we are prepared to do what it takes

20:35

to make sure we qualify for the ballot.

20:37

Once we've qualified for the ballot, which we intend to do

20:40

by the year end, we spend all

20:42

of 2024 educating the public

20:44

on mental health, on

20:47

psychedelic assisted therapies, and then

20:49

as we get closer to the vote,

20:52

and we know that there will be a lot of mayhem

20:54

because it's a big presidential election, but

20:57

we have to remind people to vote yes

20:59

on our proposition on November

21:01

5th of 2024.

21:03

And I'll have a link to the website in the show

21:05

notes, but what is the website?

21:07

It's a TreatCalifornia.org.

21:10

And is there,

21:12

you need to get signatures, but is there some

21:14

component of fundraising here? I

21:17

mean, is there something you need money for to get those

21:19

signatures? Thank

21:19

you very much, yes I do. Running

21:22

a campaign like this is enormously expensive

21:24

in California. It is on average 30

21:27

million dollars, and so

21:30

we need donations. We

21:33

have a 10-10-10 campaign. We're asking people

21:35

to donate at least $10, and

21:37

of course it'd be nice to have more, but we

21:39

think two Starbucks coffees from

21:42

the people to help us

21:44

pay for the tools that

21:47

are required to make us be

21:49

successful with this campaign.

21:52

And obviously you don't have to be in California

21:54

to donate.

21:56

No, thank you for that. In

21:58

fact, one of our biggest donors, the as

22:00

far as a conservative Republican from

22:02

Florida. The ideas are

22:04

that once we run the

22:06

trials here in California with the

22:08

FDA, we get FDA approval, these

22:11

medicines will be available to everybody in the

22:13

country. So yes, everybody

22:15

in the country can donate.

22:17

Yeah, I'm glad you mentioned

22:19

that you had a conservative Republican, at least

22:21

one backing you, because I wanna talk

22:24

about the coalition you're building

22:26

in support of this. It is surprising

22:29

and it does suggest that

22:32

there's a path here toward bypassing

22:34

some of the obvious mistakes we made

22:37

in the 60s around trying

22:39

to study these compounds and their

22:41

promise and then

22:43

also trying to enfranchise

22:46

everyone in the society to take them.

22:49

And that translation from the lab

22:52

to the streets was less

22:55

principled and governable

22:57

than seemed wise in retrospect.

23:00

Timothy Leary standing at the front of it.

23:02

I guess my next question here is, there

23:05

are some dichotomies

23:07

that seem in opposition

23:11

to one another, but they really

23:14

might not be. I mean, people

23:15

in the psychedelic space seem to think that there's

23:18

this either or decision

23:21

between focusing on decriminalization

23:24

versus research and

23:27

field research versus lab research.

23:29

You can have a medical model by

23:32

which you frame this or a spiritual

23:34

model. How do you think

23:37

about those dichotomies, Jeannie?

23:40

Or is this a hallucination we're having about

23:42

hallucinogens?

23:43

Ha ha ha, thank you. And

23:45

I've actually spent

23:46

a lot of time thinking about this.

23:49

I was born in the 60s and

23:51

raised in the 60s and 70s and witnessed

23:54

the counterculture revolution and the hippie generation.

23:57

I also was...

23:59

subject

24:02

to the dare to say no campaign by the

24:04

Reagan's. They did a really good job scaring

24:06

me to death. This is your brain on drugs,

24:09

that frying pan

24:10

and the fear. And then also feeling

24:13

the

24:13

societal unrest around the Vietnam

24:16

War and this

24:18

cultural revolution

24:20

that was happening. And the drugs

24:24

were very front and center.

24:25

So I was

24:27

in it. I didn't participate

24:29

myself in taking them, but I lived

24:32

in it. I lived through it so I could feel the

24:34

societal push and pull from

24:36

all parties.

24:38

And then not

24:39

really appreciating what it meant

24:42

when these medicines were

24:45

locked up, basically.

24:47

And then

24:48

what I've learned subsequently is that they were sort of driven

24:50

underground.

24:52

And there's a couple of paths that I wanna share

24:54

here. One is the reason why I'm sitting here

24:56

is because of the great work that was

24:58

done

24:59

out of our academic institutions.

25:01

Johns Hopkins and Yale and

25:04

NYU and now

25:07

Robin's works in front

25:09

of me. And

25:10

recognizing that these

25:13

studies were funded by philanthropists.

25:15

And philanthropists whose lives

25:17

have been changed by their use of

25:20

psychedelics early on, and I think most

25:22

famously is Steve Jobs who attributes

25:25

his LSD use to helping

25:28

build the iPhone.

25:30

So I also have great

25:32

respect

25:34

for these medicines

25:36

as a clinician. So

25:38

when you're a clinician, you have to think about

25:41

all types of patients that come

25:43

to you and you have to think about

25:45

best practices for

25:47

all your patients. And while

25:50

I appreciate and respect the psychedelic

25:52

communities that

25:55

I experience with the medicines,

25:57

I hesitate when I think about these

25:59

medicines being available to the general public

26:02

without any safety

26:04

guardrails, any guidance,

26:06

any supervision. And

26:09

I am concerned about negative consequences

26:12

and then having these negative consequences

26:14

blown up so that the

26:16

research can't proceed because

26:19

of political actions again. And

26:22

in fact, there's this wonderful group of mothers

26:25

who I recently befriended that their

26:28

children,

26:29

college age kids,

26:31

were using psychedelics

26:33

and for

26:35

different reasons ended up dying. They

26:39

were not supervised and they thought they could fly

26:41

and jumped off a bridge, which

26:42

I always thought was a

26:44

sort of a folklore story from

26:46

the government to try to scare us

26:49

all. But indeed, that can happen.

26:51

And while I appreciate

26:53

that these mothers are pushing

26:56

for safe supervision

26:58

of these medicines, that they're

27:01

not protesting and that these medicines should never

27:03

be brought to the public. In fact,

27:06

quite the contrary, they say that it

27:08

needs to be brought to the public in a safe,

27:10

responsible, and ethical way. So

27:12

allow me a little more time to share with you the vision

27:15

that I have for what the Treat Institute

27:17

will do. So we are not directly

27:19

a decram or legalization

27:22

effort. While I don't believe

27:24

people should be thrown in jail for the use

27:26

of psychedelics or cannabis for that matter,

27:29

we are not focused on decram.

27:33

Legalization is something I don't support at this

27:36

period of time because when you're bringing it out

27:38

to the general public, you have to think about

27:40

all people who are having access to

27:42

these medicines. And I believe these medicines need to

27:44

be treated with respect. The

27:47

persons need to be prepared and

27:49

educated and supervised

27:52

and allow the information

27:56

revealed in these medicines

27:58

to be shown how to incorporate them.

27:59

into their

28:00

own lives

28:02

so they can take power and control

28:04

and agency over their emotional

28:06

well-being. So what

28:09

we plan to do at the Treat Institute,

28:11

which is this $5 billion funding

28:14

agency where we will have money allocated

28:16

towards running large-scale clinical trials

28:19

with the known medicines, with known indications

28:21

like anxiety, depression, and PTSD,

28:24

as well as others, is

28:26

that it's important to look at the way these medicines

28:28

have been administered. We know

28:30

for thousands of years it's been ceremonially.

28:34

We also know they've been used in religious settings.

28:38

We know that sometimes it's used in group

28:40

settings. And there are benefits

28:42

for patients under each condition.

28:45

So I can foresee a situation

28:48

where we look at, once we show these

28:50

medicines are safe effective with the model

28:52

that's mandated by the FDA right now,

28:54

which is our two therapists in the room

28:56

at all times,

28:58

that we can look at how

29:00

does a patient respond to being in a group setting.

29:03

Likewise, how would they respond to being in a

29:05

ceremonial setting

29:07

and even a religious setting?

29:10

And can we show that it is safe

29:12

and effective for those people? And

29:15

if so, can we scale it to

29:17

maintain safety? So

29:19

I sort of look at it like going to a restaurant. And

29:22

as we defined more the criteria of

29:24

what works for the one patient,

29:27

we're leaving this model of one pill

29:30

per person for a symptom,

29:32

which said mask symptoms. We

29:35

say, what will benefit that person

29:37

more as the individual, a more of an

29:39

integrative approach? So

29:42

I may prefer to

29:43

be in a more clinical

29:45

setting with a one-on-one therapist.

29:48

And as I work through some of my issues,

29:51

I may benefit from being amongst a group

29:53

setting because there's some healing to

29:55

be gained

29:56

by these group settings

29:59

where they're safe

29:59

and people can reflect for

30:02

you the emotions that

30:04

you're working through. And there's something very beautiful

30:07

in those group settings. Likewise,

30:10

the wisdom keepers and the

30:12

way these medicines have been delivered to man for,

30:14

I mean, you could maybe even argue tens

30:17

of thousands of years, 70,000 years, have been through

30:21

these ceremonies.

30:24

And I think there's some

30:27

truism to it. And I think we need to look

30:29

at it. We need to study it and how do we safely

30:31

bring this model

30:33

to the citizens first of California

30:35

and then the rest of the country.

30:37

And lastly, we have to honor the

30:39

spirituality of this. Religious

30:43

leaders,

30:43

it's been really one of the more surprising things for

30:45

me to start exploring

30:48

religion and not, and I don't mean to organize

30:50

religion, but the spirituality behind religion.

30:53

And there's really not that much

30:55

of a difference when you're in one's altered

30:57

state of consciousness and the common descriptions

31:00

people have of feeling at one

31:04

or with this love. And

31:07

if you happen to be religious, you can

31:09

relate to it as being God or you

31:12

can feel Jesus's love or

31:14

whatever religion it is that you subscribe

31:17

to can strengthen that emotion.

31:21

So I think the Treat Institute offers

31:23

an opportunity to really address

31:26

the real healing potential of these

31:29

different therapeutic modalities.

31:31

Always keeping in mind though is how we can

31:33

scale it and scale it safely.

31:36

Well, on the point of scale, where

31:39

does the federal government come in

31:41

and how would treat

31:44

influence federal policy

31:46

if it passed in California?

31:48

Well,

31:49

we're planning on passing. And

31:52

what we're going to set out doing is

31:55

to test the safety

31:57

and efficacy of these medicines while we all

31:59

believe.

31:59

leave these medicines to be safe, there's

32:02

really no well-run study

32:04

that looks at safety.

32:07

And I think

32:09

it would be irresponsible for

32:12

us

32:12

to, if some untoward side effect

32:15

is revealed when you start

32:17

looking at thousands of patients, tens

32:20

of thousands of patients,

32:21

that something comes up that is deemed

32:24

too difficult to get around. We're

32:27

going to stop funding. We're

32:29

not intended to fund just

32:32

because we've been approved for $5 billion.

32:35

So I'm going to assume that this is safe

32:37

and that it actually works. And we're working

32:40

with the FDA and the

32:42

DEA for

32:44

approval. And when we get that approval,

32:46

it becomes available to the country.

32:49

We will continue to run trials

32:51

with different medicines and different indications,

32:54

collecting data all along the way.

32:56

I talk about our three trifecta

32:59

of our goals, which is to improve patient

33:01

outcomes, to show that it's cost-effective,

33:05

and that we make it accessible to all. So

33:08

copying the model that we did with the stem cell

33:10

agency, we actually

33:12

helped

33:13

the federal government

33:14

come up with their own guidelines and regulations

33:16

around stem cells and how they should be administered

33:20

to the rest of the country. So I

33:22

view us as working with

33:24

the existing system, bringing

33:27

evidence and data to support the

33:29

decisions that we make. I'm

33:31

not naive about this, but I believe that

33:34

we should make decisions based upon

33:36

evidence and data as best we can.

33:39

So before we get into the state

33:41

of the research, I just want to see

33:44

if I can get more information from you on the coalition

33:47

you have built in support of CREAT.

33:50

And perhaps there are

33:51

people who support you who aren't ready to go

33:53

public yet, so feel free

33:55

to edit your response.

33:57

But I just know that there's a

33:59

fairly...

33:59

bewilder in diversity of people and

34:02

groups that actually support

34:04

you. And you seem to have

34:06

quite a talent for bringing together

34:08

collaborators and supporters who

34:11

wouldn't normally find themselves

34:13

on the same team. Can you say more about that?

34:15

Well, first of all, I'm just honored.

34:18

I'm so honored to

34:21

work with the people on my

34:23

team. And I think

34:25

we are all aligned. And what I love

34:28

about this project, there's so many things I

34:30

love about this project, is

34:33

that we're showing up as very competent, credible,

34:38

experienced

34:39

human beings who are aligned to

34:41

help and serve

34:43

others.

34:44

And so in this case, I can

34:46

touch every person because there's

34:49

not one person, again, to repeat this

34:52

in our country that is not personally

34:55

touched by mental

34:56

health issues, depression,

34:58

anxiety, addiction.

35:01

Their family members

35:04

are, and certainly their friends.

35:07

So that when we're

35:08

discussing bringing a new tool,

35:11

we're bringing a new tool

35:14

to the healthcare provider

35:16

to help people that aren't otherwise

35:19

helped, and we're doing it with

35:22

rigorous research, oversight,

35:26

and not just the

35:28

black and whites of evidence as we're bringing

35:31

heart to this,

35:32

want to bring compassion

35:34

to how we're

35:36

treating people. And by

35:38

leading

35:39

with competency and

35:41

importantly with compassion,

35:44

I'm able to pull in other like-minded

35:47

extraordinary human beings, and I'm

35:49

so lucky.

35:51

So to that end, I have

35:53

to brag about my campaign manager.

35:56

This is a man who was the

35:57

senior

36:00

adviser, but essentially the right hand

36:03

of Rich Trumka, who

36:05

is the president of the AFL-CIO

36:08

unions. And if you're not aware

36:10

about unions, which I was not for

36:12

this, there are about a handful of

36:15

incredibly powerful

36:16

unions that represent the workers.

36:19

And the AFL-CIO union represents

36:21

about 60 different unions,

36:24

each representing

36:25

the workers, the backbones

36:29

of America.

36:31

They make our country

36:33

run.

36:34

These are the people who

36:36

take care

36:38

of our children, of

36:40

our,

36:41

in the hospitals, in our home,

36:44

the

36:45

nursing homes,

36:47

the plumbers,

36:49

the people who create the roads, the postal

36:51

workers, the fire departments,

36:54

the nurses, the teachers.

36:57

Because of Ramon, he's

36:59

been in his business for 30 years,

37:01

has

37:02

run hundreds of campaigns,

37:04

including supporting presidential

37:07

campaigns. His wealth

37:09

of experience is bar none. And

37:13

because he's such an honorable person,

37:15

the doors

37:17

are open for us. So he puts

37:20

me in front of

37:22

the leaders of some of the major unions

37:25

in our state and in our country,

37:28

and allows me to share the vision

37:30

of the Treat California Act.

37:32

And

37:33

every single meeting

37:36

we've had, they are supporting

37:38

us. And they are in the process of working

37:41

through the procedures

37:43

that they do to endorse us. And I'm proud

37:46

to share with you

37:48

that we got the endorsement from the

37:50

Long Beach Firefighter Union

37:52

before we even submitted our

37:54

legislation, which was the first in

37:57

union history.

37:59

We are...

37:59

also got the support of the American postal

38:02

workers for the Los Angeles area

38:04

and San Diego areas. This

38:07

ground level support from

38:10

the

38:10

people,

38:11

these are everyday workers who

38:14

are suffering themselves,

38:16

their family members are, and

38:18

they're also taking care of people

38:21

who are suffering. So when

38:23

we show up and we say, you know,

38:26

this is not a cure all, I do not think

38:28

psychedelic assisted therapy is going to cure

38:30

every person.

38:32

But I say if we can address 10%

38:35

of the population that's suffering from depression,

38:38

anxiety, addiction,

38:39

just 10% that

38:42

otherwise not treated by, we're saving, we don't

38:45

even talk about money, but we're saving

38:48

people's lives. And

38:50

those workers who, you

38:52

know, have to miss days of work

38:54

either because they're suffering from something or

38:56

their family members and they have

38:59

to take a day off to go help with a family

39:01

member who needs help

39:03

or, and the people that they're also taking

39:05

care of, it's just we're in the state of

39:07

a mental health care crisis. So

39:10

that when I'm in front of these union

39:13

leaders, and I'm talking to them about

39:15

their members,

39:17

they feel this,

39:19

this is not just another political campaign,

39:21

this is not just a way to go waste

39:22

some more, you know, money of the government,

39:25

this is actually a real solution.

39:28

And so they line up.

39:30

And so then in addition to that,

39:32

we've got the veteran community, because this is

39:34

where it all began for me with the great

39:36

work that MAPS did, you know, the

39:38

nonprofit MAPS and the clinical

39:40

trials that they were looking at the veteran community.

39:43

And of course, the veteran community is near and dear to me.

39:45

We're talking about our vets right

39:48

now, 40 suicides

39:51

or self harm

39:52

a day in our veteran

39:54

community,

39:55

in large part by PTSD.

39:59

And I have We've met

40:00

many of them, and in fact, we have

40:03

six former Navy

40:05

SEALs on our team. We

40:07

have two generals

40:09

on our team. I have a three-star

40:12

general, the former

40:14

commanding officer of the U.S.

40:16

Marines

40:17

on our team, and he has

40:20

been

40:21

educating the federal government and

40:23

the VA about the importance of funding this

40:25

research for our vets,

40:27

who right now are failing therapies,

40:30

and they have to leave the country

40:32

to undergo psychedelic-assisted therapies.

40:35

And they come back,

40:36

many of them, not all.

40:39

Many of them come back,

40:41

changed human beings. And in fact, I

40:43

like to

40:44

go off on this little tangent here for you, because

40:46

it's so important.

40:49

Rick Perry, a self-professed

40:51

knuckle-dragging Republican from Texas,

40:54

had

40:54

an aide on his team, who

40:58

was a former vet who

41:01

was struggling with PTSD, and

41:03

on average, these people, decades, has

41:05

been

41:05

struggling, barely making it to work, and all that

41:07

kind of thing.

41:08

He left the country and underwent psychedelic-assisted

41:11

therapy, and came back, and Rick Perry noticed,

41:14

and he said, what's going on, what's

41:16

the difference? And the guy shared

41:18

it with him, and he said, oh my God,

41:21

I have

41:21

to do something. So

41:23

he went to his legislation,

41:25

and in 2020, passed

41:27

a bill that afforded

41:29

$100 million in Texas to study psychedelic-assisted

41:31

therapy for

41:35

the veterans. So

41:37

the veteran community is one

41:41

that is so desperately in need, like so

41:44

many Americans are, but

41:48

the veterans are something that

41:50

the political right

41:52

can relate to.

41:54

So we picked this community

41:56

to help bridge the

41:58

divide. that is tearing

42:01

our country apart right now

42:03

and say this is not a Republican issue

42:06

or a Democratic issue. This is

42:08

a human issue

42:11

and that we have to take care

42:13

of our veterans as well as

42:15

our first responders. I've gotten to know

42:17

the firefighters. I've

42:19

learned shockingly that

42:22

suicide is the second leading

42:25

cause of death

42:27

amongst

42:28

our firefighters now.

42:30

I met with the head of the California Firefighters

42:34

Union and I'm working

42:36

with Dr. Sarah Abadi who is another

42:38

remarkable human being

42:41

and she left her practice

42:44

at UCLA as an ER physician because

42:46

she was so tired with

42:48

patients repeatedly coming into the ER

42:51

and not being able to treat them at all.

42:54

And because she's this caring, compassionate

42:56

person she's

42:58

met a few of them that actually left

43:01

patients that left the country that underwent

43:03

psychedelic assisted therapy and came back and visited

43:05

with her

43:06

and she just couldn't believe the change.

43:09

And she herself was traumatized

43:11

being in the ER during COVID and

43:14

they call it this wounded healers,

43:15

this moral

43:18

deterioration

43:18

of not being able to really to

43:20

help people and not having any support about

43:23

all the

43:23

trauma, the emotional trauma which

43:25

these are our first

43:28

responders taking care of us

43:31

and they are having problems. And so

43:33

she left and became trained

43:36

as a psychedelic assisted therapist and participated

43:39

in clinical trials. And

43:41

so they're launching a trial at the VA

43:43

again to help address this

43:46

unmet need within the VA. So

43:48

we've got the veteran community supporting

43:49

us. We've got the union people

43:52

supporting us

43:52

and now we've got the

43:55

LGBTQ community where

43:57

there are about 3 million.

43:59

voters that identify as

44:02

LGBTQ.

44:04

This community is being particularly hard

44:07

hit in today's political environment

44:10

and they are rallying behind us to help.

44:13

They're very politically active as well.

44:15

Then lastly, we're reaching

44:17

the university students. We

44:19

believe that the future

44:22

is in the youth and

44:24

they don't have the hangover, what I call the hangover

44:26

from the dare to say no campaigns.

44:29

They're much more open-minded, they're much more

44:31

interested in problem-solving.

44:34

I ache for the world that

44:36

this generation is inheriting from us,

44:39

but I also have great

44:41

hope

44:42

because it's a great generation. So

44:45

we've got the kids too that are supporting

44:47

this and they're showing up. Well,

44:49

it does sound like we have reached

44:52

a tipping point here culturally and

44:56

hopefully scientifically and it's just very

44:59

exciting to hear from

45:01

you. What is like on the front lines there?

45:04

You've named some of the clinical applications here, addiction,

45:06

depression, PTSD. We

45:08

can also add end-of-life anxiety.

45:11

Probably we can extend the list beyond

45:13

that, but then there's

45:15

also just the betterment of well people,

45:17

which I know Roland Griffiths, who

45:19

I've spoken with on the podcast before, has

45:21

been focusing on. Robin, take

45:24

any piece of this that you want,

45:26

but I think we should discuss

45:28

what compounds we're

45:31

talking about.

45:33

How do you think we should prioritize or

45:35

how are you prioritizing the

45:37

study of them? What

45:39

seems most promising? What do you think we're going

45:41

to see at the bedside first? I

45:45

mean, just what's happening here on the research

45:47

front?

45:48

Well, clearly a lot. It's

45:50

having such

45:52

an impact now. I mean, even as

45:54

we speak, another

45:56

big paper has landed in Nature Medicine.

46:00

second of two phase

46:02

three trials that MAPS sponsored,

46:06

Rick Doblin, the Multidisciplinary Association

46:08

of Psychedelic Studies and MDMA

46:11

therapy for Post Traumatic Stress Disorder.

46:14

The results of this trial are as positive

46:16

as the previous phase three trial. And

46:19

so the FDA asked for two

46:22

positive phase three trials. They've got them

46:24

now. Those results are in the

46:26

public domain. So MDMA

46:29

therapy is the furthest along in terms

46:31

of being federally approved

46:34

as a prescribable medicine.

46:37

And we know, you know, how

46:39

it has to be delivered as a combination

46:42

treatment. It's not just a drug. That's

46:44

a really important principle of psychedelic

46:46

therapy. The clues in the name is

46:49

not just psychedelics we're talking about. It's this

46:51

combination with the way the drugs

46:53

are given. And so

46:55

MDMA is front of the queue and

46:58

the forecasts are for

47:01

next year in terms of approval.

47:04

We'll see. And would

47:06

the approval be for narrowly

47:08

for PTSD or is it for these other

47:11

conditions as well like depression

47:13

or end of life anxiety or?

47:15

It's for PTSD. And those were the specific

47:17

trials. That was a specific indication. So that's

47:20

on the label. That's the first

47:22

indication on the label. But, you know,

47:25

clinicians can prescribe off label and

47:27

they do. So it's possible that

47:30

they could be providing that

47:33

intervention for other indications.

47:35

But, you know, it's sort of baby steps

47:37

once it's through the through the gate

47:40

and it will be PTSD. And it'll be a slow

47:42

process of collecting safety data

47:45

before, you know, large numbers of people

47:48

are being treated with MDMA therapy.

47:51

But it's the big milestone

47:53

is getting the first psychedelic therapy

47:56

through FDA approval.

47:58

So these state initiatives are another

48:01

thing, but that's the

48:04

classic, traditional formal

48:06

medical model with the FDA that

48:09

MDMA therapy is on the cusp of

48:12

getting that approval. And

48:14

next in the queue is psilocybin

48:17

therapy. So there's a phase

48:20

three trial currently underway sponsored

48:22

by Compass Pathways. And

48:25

there the indication is treatment-resistant

48:27

depression somewhat building on the

48:30

work that we did at Imperial

48:32

College London doing the first psilocybin

48:35

therapy for depression trial there and

48:37

that was in treatment-resistant depression published

48:40

in 2016. So yeah,

48:43

that's going to be the first phase

48:45

three trial of psilocybin therapy

48:48

for treatment-resistant depression

48:50

and I think forecast there

48:53

something in the domain of 26, 2026, so having

48:55

that work

48:59

done and that going to the FDA. So

49:02

that's kind of where we are right now. Then

49:04

there's a bunch of other compounds of course,

49:08

ketamine already is used

49:10

as a medicine and ketamine therapies

49:12

is happening right now at Sunscale

49:15

treating depression and so on, rapid acting antidepressant.

49:19

A different model and also a different

49:21

compound. I'm not sure I would

49:24

lump it in with psychedelics personally. I

49:26

think sometimes that term

49:28

is a little too fuzzily

49:31

defined or is a lack of a

49:34

crisp definition really. But

49:36

that's there and then there are other compounds,

49:38

other classic psychedelics such as LSD

49:41

trials are being done and published on LSD

49:43

therapy for depression,

49:46

also alcohol, dependence,

49:49

Michael Bogan shoots and

49:52

as DMT, that's a rapid acting

49:55

classic psychedelic. It's

49:57

given intravenously in

50:00

Some of the work that's been done at the moment, some of

50:02

the studies we've done at Imperial

50:05

with brain imaging is given that

50:07

drug intravenously. It's

50:09

the main psychedelic component of ayahuasca,

50:12

the Amazonian brew. And then there's

50:14

Bescaline, Journey Collabor, looking

50:16

at that with an interest in addiction.

50:19

So there's quite a lot. How about Ibogaine?

50:22

Yeah, Ibogaine as well. Some

50:25

very, very interesting naturalistic work

50:28

having been done with Ibogaine

50:30

in veterans with

50:33

different aspects of mental illness,

50:36

addictions, PTSD, likely

50:39

some brain injury issues

50:41

as well. And so some very promising

50:44

data coming out of that from

50:47

Nolan Williams at Stanford doing

50:50

sort of observational work

50:52

and also some brain imaging and people going

50:54

off to Mexico to have these treatments. Very

50:57

exciting, interesting compound,

51:01

exciting findings. So that's

51:03

another one too. Yeah,

51:05

there's a lot going on.

51:07

Well, notwithstanding what Jeanne said about

51:09

the need to do a lot more research

51:12

to assess the safety of these

51:14

drugs, what do we know about the

51:17

physiological toxicity or

51:19

safety of the various compounds?

51:21

I mean, because my understanding is with

51:23

something like psilocybin or LSD,

51:26

there really is no indication that

51:28

it's physically toxic apart

51:31

from the

51:32

possibility of having a bad

51:34

psychological outcome and

51:37

in the worst case, obviously hurting yourself or killing

51:39

yourself the way Jeanne described in

51:42

taking these medications out in the

51:44

wild.

51:45

But

51:46

with a drug like MDMA or

51:49

ketamine, you're talking about something that where

51:51

there really is an LD50,

51:53

a lethal dose that

51:57

could be easily specified.

52:00

and perhaps there's some physiological

52:02

toxicity that we know about in those

52:05

drugs, even at safe doses,

52:07

many times repeated. So what can you say

52:10

to safety? In

52:12

reality, there are a lot of people listening to this

52:14

who are,

52:15

you know, they might be very supportive of

52:18

everything

52:18

we're talking about here and

52:21

building a well-governed therapeutic

52:23

model for helping people

52:26

with the most relevant compounds. But

52:28

in reality, there are also millions of people who

52:31

have taken these quote recreationally,

52:33

you happen to be talking to one of them right

52:35

now, and in

52:37

making decisions about what to take, there

52:40

are differences here. And obviously, we should add

52:42

the caveat that not

52:45

everyone should take these compounds,

52:47

certainly not in a situation where

52:50

they haven't seen to all of the necessities

52:53

of set and setting.

52:55

And I've talked about that in

52:57

great length on other podcasts with people like Roland

53:00

Griffiths and James Fadiman and others.

53:02

But

53:04

there are just differences here, and we

53:06

should also stipulate that in many cases, unless

53:08

you're in the presence of something like psilocybin

53:11

mushrooms, you're taking something that

53:13

unless you've had it studied in a lab, you don't you can't

53:15

be sure you're taking the compound

53:17

you think you're taking. So all of those caveats

53:20

aside, in the presence of the actual

53:22

compounds, can you differentiate

53:24

any safety concerns

53:26

at the physiological level?

53:29

Yes, absolutely. I mean, the compounds are often

53:32

too easily lumped together as, you know, say

53:34

psychedelics, but they're really quite

53:36

distinct and the toxicity profiles

53:38

are quite distinct. I mean, the

53:41

dose makes the poison, so even those

53:43

compounds with the better

53:46

therapeutic indices, meaning

53:48

that a therapeutic dose

53:51

to a dangerous or lethal

53:53

dose could be massive. And

53:56

in the case of say psilocybin, it is

53:58

a very large therapeutic index. so

54:00

that's very positive.

54:02

But tighter

54:04

with LSD, actually, LSD is very potent,

54:07

so it is not so hard

54:09

to overdose on LSD. And

54:11

then it's not just a psychological risk,

54:13

but there's also some physiological risk as well.

54:16

MDMA carries some toxicity

54:19

in high doses. That's some evidence of neurotoxicity.

54:22

But in therapeutic doses, it seems unlikely.

54:26

When you have other organs where

54:29

MDMA can be toxic to those as well,

54:31

the liver, ketamine has

54:34

high toxicity, some

54:37

appreciable toxicity for

54:39

the bladder and

54:41

the metabolites of that. So that can be a problem.

54:44

There have been cases of people having their bladders

54:46

removed from excessive

54:47

use of ketamine.

54:50

Ketamine is also addictive, right?

54:52

It is another part of the elevated

54:55

risk profile, I'd say, with ketamine. I

54:58

see ketamine. Ketamine

55:00

therapy is a kind of placeholder for

55:03

interventions like psilocybin therapy coming

55:05

down the line. A number of different

55:08

angles in which psilocybin therapy

55:10

I think is superior to ketamine. The toxicity,

55:14

it's got the rapid action, but it's also

55:16

got a more enduring action. In

55:18

my mind, it's a deeper quality

55:21

of action as well. A

55:23

lot of effect on

55:26

psychological insight, emotional

55:28

release that perhaps you don't get

55:31

so easily with ketamine. That's

55:34

probably part of the reason why it has

55:36

a longer tail in terms of a therapeutic

55:39

response, psilocybin versus ketamine. So

55:42

a lot of differences. We talked about

55:44

Ibogaine a little bit. There's some cardio

55:48

toxicity questions.

55:51

Actually, that's really hampered some of the clinical

55:53

research with that compound. There

55:56

hasn't been much in terms of control

55:58

studies with Ibogaine because of... question

56:00

marks over how safe it is in

56:02

terms of, you know, cardio

56:06

risk.

56:07

Most people don't differentiate ketamine,

56:10

which is an analgesic,

56:12

and MDMA, which is a type

56:14

of amphetamine, don't really

56:16

fall into the class of a true

56:19

hallucinogen, which are mainly tryptamine

56:21

derivatives. And so

56:22

I also want to point out that both ketamine and

56:24

MDMA are addictive and

56:27

have different physiological properties. I'm not

56:29

really sure on MDMA. Yeah. Okay.

56:33

To be explored. Because amphetamines

56:35

in general.

56:36

Amphetamines, yes. But MDMA is

56:38

quite different to other amphetamines

56:41

in terms of... Amphetamines as

56:43

a class have that very strong dopamine

56:45

release, but serotonin releases 10 times

56:48

that of dopamine. So

56:51

it's quite distinct, I would say, from

56:53

most other amphetamines. And also

56:56

there isn't clear evidence that people would take

56:58

MDMA in a sort

57:01

of Moorish way, you know, craving.

57:04

So what I'm hoping, of course, is that we can actually

57:06

really

57:06

study this and track data and

57:09

track and determine if it is indeed

57:11

addictive or not. But until we

57:13

have the funding to do this, these are

57:15

all open-ended questions.

57:17

And I just also wanted to highlight, I

57:19

think for ketamine, I think one of the best

57:21

applications will be for acute suicidality.

57:24

Some of the studies are showing for people

57:26

that are showing up acutely suicidal

57:28

in the ER. Oftentimes you sedate

57:30

the person, you admit the person, you put them on a

57:32

hold, and you wait

57:35

until the SSRIs kind

57:37

of kick in as a sort of standard of care.

57:41

But ketamine, the fast-acting effect,

57:43

appears to allow the patient

57:45

to feel not depressed

57:48

for a moment. And in that feeling,

57:51

they can hold onto that thread,

57:53

actually, of hope, of not always

57:55

feeling so depressed, which

57:57

is what leads people to be suicidal.

58:00

So,

58:02

but when we're talking about what we're going

58:04

to be studying in the Treat Institute

58:07

is mostly the true

58:09

hallucinogens that don't have patents

58:11

on them too because they don't get funding for

58:15

pharmaceutical companies don't get involved in them. And

58:17

so

58:18

I think it's really important to look at all

58:20

the qualities of these medicines and the impacts

58:23

on the individuals. And I also want to highlight

58:25

that what we hope to do is we're

58:27

going to create what will be the largest

58:29

bioinformatics data bank in

58:31

the world focused on mental health.

58:34

And

58:34

of course we'll make it cyber secure and

58:37

anonymous and people patients will

58:39

opt in. But we plan on

58:41

doing complete geniogenomics sequencing,

58:44

genetic sequencing, including all the omics,

58:46

the panomics, the proteomics, the

58:49

epigenetic changes, and then

58:51

also including the information coming

58:53

from all the scanning devices, the fMRI's,

58:56

the wearable devices, and then

58:58

overlay that with what we call the phenotypic

59:00

expression. So patient presents with

59:03

anxiety, depression,

59:05

PTSD, and oftentimes complex

59:08

stuff and or addiction as

59:10

well as all the other mental

59:13

health issues we can call.

59:15

And that

59:16

by understanding perhaps the biology

59:18

of say Robin sitting across the table from

59:21

me has a different makeup of his serotonin

59:23

receptors and his dopamine receptors that may

59:25

be more menable to a

59:27

particular type of psychedelic

59:30

versus another type. And

59:32

so it's truly becoming more patient

59:35

specific what is best for him,

59:37

what will improve his probability

59:40

of healing from these medicines or

59:42

gaining insights that empower him to

59:44

incorporate new

59:46

habits in his life.

59:49

And likewise,

59:50

he may be

59:52

more open to being in a group

59:54

therapy to start

59:55

or not.

59:56

Maybe he wants to be in a one

59:59

on one together.

59:59

get more comfortable with the medicines

1:00:02

and then be in a group therapy. So

1:00:04

we don't see it as such a

1:00:06

prescriptive therapeutic approach

1:00:09

where each person gets this

1:00:11

amount for this amount of time under

1:00:13

these settings. I think it's

1:00:15

important to talk about the

1:00:18

variety by which we can learn to

1:00:20

heal and make that available.

1:00:22

So I'd add that. On

1:00:25

this issue of further research,

1:00:27

study by study, can you give me

1:00:29

a sense of what

1:00:31

a well-run study costs

1:00:34

at the moment?

1:00:35

Sure.

1:00:36

Well, gosh, a well-run

1:00:39

study, how'd you define that? Yeah. I

1:00:41

mean, I know there's a wide range and Jeannie

1:00:44

just floated the idea that we would be tracking

1:00:46

thousands of people ideally in studies,

1:00:49

but the sorts of studies that are being run

1:00:51

now, let's say

1:00:52

the MAP study that's in

1:00:55

stage three clinical trials,

1:00:57

what do those studies cost?

1:00:59

Hundreds of millions. Yeah, I mean, I think it's

1:01:01

fair to say, I mean, it took MAPs 37 years, I believe,

1:01:04

from its beginning to

1:01:05

finish two phase three trials

1:01:08

to the tune of about $150

1:01:09

million. So

1:01:12

it took 37 years.

1:01:14

So what

1:01:16

we hope to do is because we have this

1:01:19

great clinical trial infrastructure here in

1:01:21

our state with incredible academic institutions

1:01:24

as well as contract research organizations

1:01:26

will determine which ones can be most

1:01:29

efficient and most cost effective. We can

1:01:31

run trials with thousands of patients in

1:01:33

a short period of time

1:01:35

because we want to try to find a therapy

1:01:37

that actually is

1:01:38

safe and efficacious and then

1:01:40

determine under what parameters should

1:01:42

those patients receive this medicine.

1:01:45

Yeah,

1:01:46

you know, there's phase three trials,

1:01:49

let's say two sample, what's it gonna be? In

1:01:51

the ballpark of 300 people or something.

1:01:54

300 people, it's a very

1:01:56

difficult number to quantify because I've run another

1:01:59

startup company.

1:01:59

and depending upon who you get

1:02:02

and how you get and how many people you have to have in

1:02:04

it. But

1:02:05

it's on the order of, I mean, I think

1:02:07

the smallest you can do is almost

1:02:11

a million, maybe,

1:02:12

really realistically

1:02:16

with people that you know. But on average,

1:02:18

I think it'd be fair to say that it's at least

1:02:20

a hundred million.

1:02:21

Yeah. Yeah. But

1:02:23

of course, there's so many different types

1:02:26

of studies and trials. And the

1:02:28

first investigator led trials like

1:02:31

the treatment resistant

1:02:33

depression trial we did at Imperial.

1:02:35

We got some UK Medical Research

1:02:37

Council money to make

1:02:39

that possible. And that was, let's see,

1:02:42

the first amount was,

1:02:44

I think it was even half a million.

1:02:46

So that ended up

1:02:49

being a 20 patient trial

1:02:51

open label because of some philanthropy

1:02:53

that came in. But for

1:02:56

a long time, we were

1:02:58

very much working on fumes.

1:03:01

We had volunteer staff working

1:03:04

on the trials and we were just doing

1:03:06

it kind of out of passion as much as anything.

1:03:09

Things have changed a huge amount since then.

1:03:12

What do you think is happening in

1:03:14

the brain at this point, Robin,

1:03:16

when we take

1:03:18

one of the classic serotonergic psychedelics

1:03:21

or LSE psilocybin? I

1:03:23

mean, I'd be interested to know what you think is happening

1:03:25

with MDMA as well. But I

1:03:28

think you said you did an fMRI study

1:03:30

on DMT too. Give me

1:03:33

the mapping that

1:03:35

we are reasonably confident

1:03:38

in at this point.

1:03:39

Yeah, I think it's fair to say

1:03:41

we're reasonably confident now because we've

1:03:43

had, personally, I've

1:03:46

done three studies with three classics.

1:03:48

DMT was the most recent. And

1:03:51

so there are some principles that

1:03:53

are emerging. One of them

1:03:57

is that if we look at the

1:04:00

at brain networks, which is more the

1:04:02

way that we think of human

1:04:04

brain function and making mappings to

1:04:07

high-level cognition and

1:04:10

conscious states. We're

1:04:12

much more thinking about brain networks

1:04:15

now, their dynamics. And

1:04:18

there we see that across the board

1:04:20

with psilocybin, LSD, DMT,

1:04:23

you see a breakdown in

1:04:25

the integrity of brain

1:04:27

networks. And this is actually quite true across

1:04:31

a repertoire of major brain networks,

1:04:33

but especially so in high-level

1:04:36

brain networks, networks

1:04:39

that we describe as transmodal, meaning

1:04:41

they don't just do one thing, but

1:04:43

they do a few things. They're involved in a lot,

1:04:45

including the highest level

1:04:48

aspects of human cognition

1:04:50

or consciousness. So we see the

1:04:52

integrity of those networks, the different

1:04:55

nodes, the different parts that make them up,

1:04:58

that breaks down. And at the same

1:05:00

time, those networks

1:05:03

open up their communication profiles.

1:05:05

So rather than being very

1:05:08

segregated from each other, very

1:05:10

insular, they start to communicate

1:05:13

more with each other. And

1:05:15

we can describe that a few different ways.

1:05:17

We could call it desegregation, network

1:05:19

desegregation. So you have within

1:05:22

network disintegration, and

1:05:25

you have between network desegregation.

1:05:27

At the global

1:05:31

level, as in the whole of the brain,

1:05:33

you could describe a global

1:05:36

increase in functional integrity.

1:05:39

There's always more, of course,

1:05:41

and I haven't even gone into the pharmacology

1:05:44

that with the classic psychedelics,

1:05:46

one of the ways that we could define them, I

1:05:48

don't think we should only

1:05:51

define them this way because it glosses

1:05:53

over the phenomenology, which I actually think

1:05:56

is key for a definition of

1:05:58

these drugs. But we do know with

1:06:00

a high degree of confidence, really mostly

1:06:04

from the human research, and I think

1:06:06

that is pivotal here actually, we

1:06:09

know that stimulating directly a certain

1:06:11

serotonin receptor is

1:06:14

key to their action. And we know that because there's

1:06:16

a very tight positive correlation

1:06:18

between the affinity or stickiness or

1:06:21

binding potential of a given

1:06:23

psychedelic for that receptor specifically

1:06:26

and its potency. Are these still

1:06:28

the 2A receptors? Yeah, the serotonin

1:06:30

2A receptors. Yeah, so higher affinity,

1:06:33

more potent. LSD, very

1:06:35

high affinity, very potent compound.

1:06:38

And then we also know that if you pretreat

1:06:41

with a serotonin 2A receptor

1:06:43

blocker, we call those antagonists, then

1:06:46

the psychedelic can't hit its target

1:06:48

because it's blocked and you don't trip. You

1:06:51

don't have a psychedelic experience. And then

1:06:53

we also have more recent

1:06:55

evidence that you can abort a trip by

1:06:58

giving the blocker after giving

1:07:00

the psychedelic. So these

1:07:03

are just a few examples of really

1:07:05

converging evidence on the

1:07:08

2A receptor as being the key

1:07:10

initiation site to where

1:07:12

it all begins in a sense with the action

1:07:15

of at least the classic psychedelics.

1:07:18

Is MDMA also active

1:07:20

through the 2A receptors?

1:07:22

Not directly, but really

1:07:24

the key sort

1:07:26

of signature pharmacological

1:07:28

action of MDMA is its

1:07:30

serotonin release. Yeah,

1:07:33

it's really pretty unique

1:07:35

in that sense. There aren't many compounds that

1:07:38

release serotonin as

1:07:40

potently. Yeah,

1:07:42

I mean, we have the selective serotonin reuptake

1:07:44

inhibits antidepressants,

1:07:46

Prozac-like drugs, but

1:07:50

they're just blocking the reuptake.

1:07:52

MDMA actually stimulates the release

1:07:55

of serotonin. So I sometimes

1:07:57

playfully call it a turbo.

1:08:00

SSRI, sort of spitting

1:08:02

out serotonin into the the synapse,

1:08:05

that gap where all the key you

1:08:07

know chemical information

1:08:09

transfer happens between.

1:08:11

Oh, in some possible

1:08:13

dystopian future, it will be sold under that

1:08:15

name in a drug store near you to

1:08:18

teenagers. What do you make

1:08:20

of the fact that DMT is actually

1:08:23

an endogenous neurotransmitter? Do

1:08:25

we know what it might be doing at this

1:08:27

point on its own at its ambient

1:08:30

level?

1:08:31

We don't, but it's one of the great mysteries.

1:08:33

Rick Strassman has

1:08:36

classically speculated on that in the

1:08:38

spirit molecule. It is there,

1:08:41

you can find it in the body

1:08:43

and you can find it in the brain. There's also

1:08:45

some rodent evidence now

1:08:47

that it's released or at least its

1:08:50

concentration spikes up in

1:08:52

a dying brain. The

1:08:55

problem there is a specificity question

1:08:57

because a lot spikes up in a

1:08:59

dying brain because cells are dying

1:09:02

and spilling their content in a sense. So

1:09:04

serotonin itself spikes up

1:09:06

massively. So there's just a little

1:09:08

bit of a question mark on there.

1:09:10

Some people have also questioned whether there's

1:09:12

enough of DMT endogenous

1:09:16

to really have an appreciable sort

1:09:19

of functional effect. But then people say, well, you

1:09:21

know, during these extreme states as

1:09:23

was shown in that rodent work, maybe

1:09:26

it spikes up and then maybe then

1:09:28

it, you know, that could explain things

1:09:30

like the near-death experience because you

1:09:32

enter a psychedelic-like

1:09:34

stay through the action of this endogenous

1:09:37

psychedelic. It's a very

1:09:40

fun hypothesis, but

1:09:42

that's kind of what it is still right

1:09:44

now, a hypothesis.

1:09:48

There are overlaps in the phenomenology.

1:09:50

It's just whether or not we can commit

1:09:52

to DMT specifically,

1:09:55

you know, responsible, being responsible

1:09:57

for that phenomenology. Or,

1:09:59

for example,

1:09:59

you know, it could be established

1:10:01

in dodgiest neurotransmitters

1:10:03

like serotonin, you know, and that's spiking

1:10:06

up and hitting its 2A targets

1:10:08

and so on.

1:10:10

Is there any prospect,

1:10:13

do you think, in the near term of

1:10:15

us

1:10:15

developing and discovering new compounds that

1:10:20

we just haven't

1:10:21

named here? I mean, we're talking about,

1:10:24

we can almost count on one hand, the number

1:10:26

of compounds we're excited to study, but

1:10:28

I remember meeting the rogue chemist

1:10:31

Sasha Shulgin, I don't know if either of you

1:10:33

ever knew him, but

1:10:34

you know, to hear him

1:10:37

talk about it, it sounded like if you

1:10:39

just, you know, walk into his house, he

1:10:41

could produce, you know, hundreds

1:10:43

of different compounds that he had

1:10:46

privately experimented with and catalogued.

1:10:48

He wrote some very interesting

1:10:50

books on that topic and so

1:10:53

there's this kind of this thicket of adjacent

1:10:56

compounds that are sitting there

1:10:58

to be explored, I think

1:11:00

some of which were described by him as

1:11:02

a don't go there again, but

1:11:05

what do you think about the prospect that we

1:11:07

are at

1:11:08

the very beginning of exploring

1:11:10

in a much wider search

1:11:12

space?

1:11:14

Well, we are. I mean, we don't know

1:11:16

what we don't know, but people are searching

1:11:18

vast libraries, even sort of,

1:11:21

you know, libraries of billions

1:11:23

of potential molecules

1:11:26

by doing, you know, in silico

1:11:28

modeling, computer modeling and looking at

1:11:30

how these possible chemicals

1:11:33

dock at, say, the serotonin to a receptor.

1:11:36

So, you know, there could be almost

1:11:39

endless possibilities there in terms of

1:11:41

new drugs. Yeah, so,

1:11:44

and we could play with the pharmacology and

1:11:47

try and find, you know,

1:11:49

drugs where we could reduce

1:11:51

some of the off-target effects.

1:11:54

For example, serotonin 2B

1:11:57

receptor stimulation is a problem. If

1:12:00

you have drugs that do that, it can

1:12:03

fatten up the heart valves

1:12:06

and cause this valveopathy.

1:12:12

You have compounds like psilocybin,

1:12:14

which is metabolized into psilocin,

1:12:17

actually hitting the 2B receptor.

1:12:20

That's been a question mark for things like microdosing

1:12:23

or regular use of low doses

1:12:25

of psilocybin. We

1:12:28

could improve on the drugs. In

1:12:32

a sense, that's a given and to the

1:12:34

point that we don't know what we don't know. Science

1:12:37

is always iterative and it will

1:12:39

go on forever, improving, advancing

1:12:42

how we understand things. But there

1:12:44

is another thing to say, which is we

1:12:46

could be very drug-centric here. If

1:12:49

fundamentally with psychedelic therapy,

1:12:51

we have a combination treatment, then maybe

1:12:54

there's a lot to be learned

1:12:57

about the other side of this,

1:12:59

the other side of this biopsychosocial

1:13:03

intervention that isn't just

1:13:05

giving the drug. So we

1:13:07

can make advancements there too.

1:13:09

Sam, I'd like to share a final folklore

1:13:12

story, if you mind, about the Shoguns.

1:13:15

Somebody on my team spent

1:13:17

quite a bit of time with him. He was fresh

1:13:19

out of college at Princeton way back when

1:13:21

and got his PhD in

1:13:23

philosophy and taught at Yale. I

1:13:25

forgot, I met him. What was his name again? David Blinder. It's

1:13:31

just a wonderful story, but he befriended

1:13:33

the Shoguns and participated regularly.

1:13:36

Sasha would

1:13:38

create these compounds and

1:13:40

pass them out to everybody and ask

1:13:43

them what the side

1:13:45

effects were, and then he would meticulously write them down. So

1:13:49

upon his death and his wife's deaths recently,

1:13:51

there is the Shogan Library, and

1:13:53

there are about 200 compounds that

1:13:56

there are efforts to help and

1:13:58

preserve them into.

1:14:00

bring them to the

1:14:02

world of research. And one effort

1:14:05

which I hope we will be able to do is if

1:14:07

there are some of them that are deserving

1:14:09

of studying that we can look at it.

1:14:11

Because I also want to point

1:14:12

out in addition to, and I want to go into

1:14:14

what Robin just left off

1:14:17

about the spiritual part of this too, because I think

1:14:19

it's really important and would like to bring that up.

1:14:21

But there are other treatment paradigms

1:14:23

that this is really seemingly promising for,

1:14:26

and the traumatic brain injury is one. The

1:14:28

neurodegenerative diseases, because

1:14:31

of the neuroplasticity, whether there's growth factors

1:14:33

in there that seem to perhaps be

1:14:35

a disease modifying compound for Alzheimer's.

1:14:39

I know there's one study that was using

1:14:41

psilocybin, I believe, for the

1:14:43

treatment of new onset depression that's oftentimes

1:14:45

associated with neurodegenerative disease.

1:14:48

In this particular case, it was Parkinson's disease.

1:14:51

And they noticed that the

1:14:53

motor symptoms were improving. So not only did

1:14:55

their depression symptoms improve, but they

1:14:57

noticed that the

1:14:59

motor symptoms improved. So

1:15:01

I think

1:15:02

that there is room for these medicines

1:15:04

to be studied

1:15:06

for different applications. I'm

1:15:08

also aware of a scientist who's using this

1:15:10

to study inflammatory diseases,

1:15:13

and particularly asthma. And

1:15:15

I think, wow, when I was in medical

1:15:17

school or even practicing medicine, when you hear about

1:15:20

a cure-all, right? I

1:15:22

think of this snake oil salesperson

1:15:25

peddling the goods that this is going to

1:15:27

help everything. But these are actually well-run

1:15:30

studies. And so it

1:15:32

just begs the question that I think that there

1:15:34

are many applications that are possibilities

1:15:38

and that we need to look at them.

1:15:40

And then I want to leave that and go back

1:15:41

to where Robin left off, because I had a couple questions

1:15:44

for you, Robin. I was so curious about

1:15:46

this study, and you mentioned

1:15:48

about desiloing or

1:15:50

desegregating, you said, certain areas of

1:15:53

the brain. And I wonder if you would just

1:15:55

elaborate on that a little bit more, because it's something

1:15:57

that I have personally felt in my

1:15:59

own brain. And I want to share that by

1:16:01

way of saying if you know I've studied

1:16:04

as a biochemist and I have that area of my

1:16:06

brain is well developed in math and then

1:16:08

I'm also, you know, an athlete there's

1:16:10

a different part of my brain that works and I like music

1:16:13

and that's a different part of my brain that works and then the

1:16:15

ability to think abstractly is a different

1:16:17

part of my brain. And I just

1:16:20

personally have noticed that since using

1:16:22

these medicines therapeutically that

1:16:25

I feel like I have access

1:16:27

to these otherwise siloed

1:16:30

parts of my brain are now

1:16:32

seemingly available to me

1:16:34

at the same time. And

1:16:37

I was wondering if you could speak to that in some of the fMRI

1:16:39

studies that you I thought you participated

1:16:41

in them

1:16:43

or you're certainly aware of them. Oh yeah. Yeah.

1:16:46

Did you run that trial, Robin? Probably. Yeah.

1:16:49

Well, yeah, of course, we

1:16:52

have to be a bit careful what we feel

1:16:54

in our brain. But

1:16:57

yeah, I mean,

1:17:01

yeah, there's a few different principles

1:17:03

as I said. You

1:17:07

have in a sense organization

1:17:10

and structure that's

1:17:13

recognized in the brain like say a brain

1:17:15

network that you can

1:17:17

then see decrease

1:17:19

in its organization

1:17:22

under drugs. So that's an

1:17:25

example of that disintegration or a

1:17:27

loss of structure or a loss

1:17:30

of regularity, a

1:17:33

dysregulating action. So that

1:17:35

stuff breaking down. I

1:17:38

call that, the hypothesis

1:17:40

I introduced about 10 years ago called the entropic

1:17:42

brain hypothesis, which is

1:17:46

somewhat related here. You can think

1:17:48

of entropy in a thermodynamic sense

1:17:50

of degradation, things

1:17:52

breaking down the arrow of time. But

1:17:55

there's also this intriguing possibility

1:17:58

that we have less of a good handle

1:18:00

on, which takes

1:18:03

us back to the definition of these compounds,

1:18:05

at least through classic psychedelics,

1:18:08

psyche as mind

1:18:11

or more accurately soul, and

1:18:13

then the other term means to make manifest

1:18:16

or visible.

1:18:17

So

1:18:18

while we have aspects

1:18:20

of brain function dysregulating

1:18:23

or breaking down, what

1:18:25

of the ordinal

1:18:29

order amidst the disorder

1:18:31

or the cosmos in the chaos, as Carl Jung

1:18:34

would say, what accounts for

1:18:36

that? What accounts for the insight? What

1:18:38

accounts for the apparent

1:18:43

seeing of things, of content?

1:18:45

Say on DMT, classic

1:18:48

aspect of the phenomenology there is that

1:18:50

people report these apparent

1:18:53

encounters with other sentient beings.

1:18:56

What's doing that? I know that really

1:18:59

throws people when they have the

1:19:01

experience, they're left bamboozled thinking

1:19:03

that it must be something beyond

1:19:06

the brain. Of course, I think that's

1:19:08

a false inference. Well,

1:19:10

that brings us back

1:19:12

to your naive thesis

1:19:14

that you mentioned a while ago, which is by

1:19:18

analogy to dreams. Dreams

1:19:21

are

1:19:21

an experience where we routinely

1:19:24

seem to feel an experience

1:19:27

that we're in the presence of other

1:19:29

autonomous beings. Everyone's

1:19:34

had that experience. You're talking to somebody

1:19:36

who you really think is there and then you wake up and you realize

1:19:39

it wasn't what you thought it was.

1:19:41

Does that offer some

1:19:43

phenomenological clue to what might be happening

1:19:45

during the DMT flash?

1:19:48

Yeah, I think it does. I think it's a useful

1:19:50

analogy. The dream

1:19:52

is entirely compelling.

1:19:58

There's no doubt that your experience is there. experiencing

1:20:00

that in the moment, and yet you're

1:20:02

not, you know? I guess the

1:20:04

one thing that

1:20:05

fans of some metaphysical

1:20:08

claim here would want to say

1:20:10

at this point is that that doesn't

1:20:12

explain the apparent convergence

1:20:15

phenomenologically in the reports

1:20:18

that people give of the kinds of entities

1:20:21

they encounter while on DMT.

1:20:23

I don't know. I remember Rick Strassman's book

1:20:26

on this topic, but I haven't followed

1:20:29

whatever research has been done of late. I

1:20:31

can imagine it'd be somewhat hard to find

1:20:34

a volunteer for a DMT

1:20:36

study who had never heard Terrence

1:20:38

McKenna or anyone else rave about the

1:20:41

phenomenology. How impressive

1:20:43

is that convergence of report

1:20:46

on what the landscape looks

1:20:49

like

1:20:49

during the experience? There's some convergence,

1:20:52

but of course, I say of course,

1:20:54

there's this thing called the collective unconscious

1:20:56

and archetypes and certain

1:20:59

human themes that get in

1:21:01

a sense imprinted because we experience

1:21:04

them a lot, like the hero's journey.

1:21:06

It's classic, it's arguably universal

1:21:09

and somewhat culturally independent

1:21:12

at the most basic level, at the most foundational

1:21:15

level. It would

1:21:18

be surprising if it was any other

1:21:20

way that we wouldn't have archetypal-like

1:21:23

experiences under

1:21:26

these compounds, experience

1:21:29

tricksters that can morph

1:21:31

into a maternal archetype,

1:21:34

a mother archetype, and

1:21:36

then switch back again. That's the

1:21:39

human nature, the human psyche.

1:21:42

So I don't think there's anything that should

1:21:45

draw us into beyond

1:21:47

the brain kind of speculations

1:21:50

based on any kind of convergence.

1:21:52

It just speaks to, in my mind, the collective unconscious.

1:21:55

Yeah,

1:21:56

I could go on. I

1:21:58

mean, a dominant Model in cognitive

1:22:00

neuroscience now is one

1:22:03

that a friend and colleague

1:22:05

of mine, Shamil Chandarya, spoke about

1:22:07

recently on your podcast, the

1:22:10

hierarchical predictive processing

1:22:12

model, very

1:22:14

compelling model of how the brain works

1:22:16

in a sense that's increasingly

1:22:18

influential, including in psychiatry.

1:22:22

And there, the model says that we experience

1:22:24

the world through these generative models, this

1:22:27

kind of coarse graining of what's what.

1:22:29

But the key principle is that there's

1:22:32

a dominant directionality

1:22:34

to the information flow that in

1:22:36

a sense you could describe as top-down. And

1:22:39

that's what's carrying the prediction, carrying

1:22:41

the inference, is that we're experiencing

1:22:44

the world through our internal

1:22:47

models. That's what's

1:22:49

dominating the handshake, if you

1:22:52

want, is that top-down model, model-first

1:22:55

kind of flow. Into that mix,

1:22:57

I dropped psychedelics,

1:22:59

in a sense, and proposed

1:23:02

that what psychedelics do

1:23:04

is they impact what's

1:23:07

called in technical terms

1:23:09

the precision weighting, but in more sort

1:23:11

of accessible terms we could just call the

1:23:13

weighting the weighting or

1:23:16

the influence of the predictive

1:23:18

models and psychedelics dial

1:23:20

it down so that our

1:23:23

internal models are less convincing

1:23:26

and stuff can come

1:23:28

up because of that. Yeah.

1:23:31

I mean, it's just in a very

1:23:33

basic psychological sense when you

1:23:35

look at

1:23:36

why people suffer, and this is, you

1:23:38

know, weaving aside even

1:23:41

extreme clinical cases, just the ordinary

1:23:44

routine suffering of ordinary people who

1:23:46

may not have any diagnosis

1:23:48

to speak of. So much of

1:23:50

the character of our suffering is this

1:23:54

imprisonment in certain patterns

1:23:56

of thinking and reacting

1:23:58

to just ordinary experience.

1:23:59

I mean, we're ruminating all day

1:24:02

long. We're having a very

1:24:04

unprofitable conversation with

1:24:06

ourselves that, in my view,

1:24:08

also impressively resembles

1:24:11

what it's like to be asleep and dreaming.

1:24:13

I mean, there's something about identification

1:24:15

with thought that is just

1:24:18

as spurious in the end as

1:24:20

being asleep and dreaming and not knowing that

1:24:22

you're dreaming. And

1:24:24

it's pretty easy to see that certain

1:24:26

ways of disrupting that

1:24:28

would offer a kind of – disrupting

1:24:30

and resetting would offer a kind of opportunity

1:24:33

for relief. Hmm.

1:24:35

Quite. Yeah, I mean, it's

1:24:38

true of psychopathology, I think, mental

1:24:40

illness, so much of it, depression and erecture.

1:24:43

You know, these habits of

1:24:46

thinking, getting fixated on

1:24:48

certain ideas in a sense. You

1:24:51

know, that we're worthless or that we're

1:24:53

too big. But

1:24:56

also, it's the case, you know, in domains

1:24:58

that we wouldn't ordinarily think of as psychopathological

1:25:02

or of mental illness. You know, even politics

1:25:05

or religion, we can – I

1:25:07

borrow a term from evolutionary science, which

1:25:10

is canalization. Hmm. It

1:25:13

means the entrenchment of

1:25:15

traits so that they become

1:25:17

stamped in and resistant to

1:25:19

change, resilient to change.

1:25:22

It's the opposite, actually, of

1:25:24

the most basic definition of plasticity,

1:25:27

which is the ability to be – to

1:25:29

change, to be shaped or molded. Yeah.

1:25:32

And canalization is the inverse of that. You know,

1:25:34

but even our very sense of self or

1:25:37

identity or ego is

1:25:39

a product

1:25:40

of the same

1:25:41

canalization or identifying

1:25:44

with thoughts.

1:25:45

Yeah.

1:25:46

Yeah. And on that point, how

1:25:48

much of it is the story still

1:25:51

of the default mode network being

1:25:53

down-regulated during the

1:25:56

psychedelic experience? Is that still part

1:25:58

of the signature of?

1:25:59

Yeah, I'd say we've moved on a

1:26:02

little bit. That was the finding of ours

1:26:05

in the first FMRI study that

1:26:07

we did. In fact, the first FMRI

1:26:09

study of Salasibin 2012, we

1:26:12

found that the

1:26:14

default mode network was especially implicated.

1:26:18

Its integrity broke down since I

1:26:20

was describing this disintegration effect.

1:26:23

And other changes also kind of

1:26:25

pointed at this default mode

1:26:28

this dominant network

1:26:30

in the brain that is

1:26:33

kind of capital city in the brain. It's

1:26:36

a hub of connectivity of high

1:26:39

metabolism, tonically

1:26:41

active in the background, hence default

1:26:43

mode. Yeah, so we saw that

1:26:45

that dysregulated and in a sense

1:26:48

disintegrate under the Salasibin.

1:26:50

And we also saw that effect correlate

1:26:52

in different analyses over time

1:26:54

with ratings of ego dissolution. So

1:26:57

we made a kind of one-to-one mapping

1:26:59

there that maybe it's related to that

1:27:01

experience of ego dissolution. That

1:27:04

had a big impact as an idea and it sort

1:27:06

of became in a sense a canalized

1:27:09

story in itself. I'd say

1:27:11

we've moved on a little bit because I

1:27:13

think it was a little too

1:27:16

centered on one particular network. There

1:27:18

are other neighboring networks also

1:27:21

high level that break down

1:27:23

under psychedelics and are also implicated

1:27:26

or that breakdown correlates with

1:27:28

ratings of ego dissolution as well.

1:27:31

So I just think it was too focused

1:27:33

on one particular network. I don't think it's wrong

1:27:36

as an idea. There's just more

1:27:38

to it

1:27:39

as there always is.

1:27:42

How about the critical window period that Gull

1:27:44

is introducing? Well, that's a nice one too.

1:27:46

Yeah, so we

1:27:48

have these periods early in life

1:27:51

when we're hyperplastic.

1:27:53

Just think of kids and

1:27:55

how they can pick up languages

1:27:57

so easily in the early years. And

1:28:00

then that window of plasticity

1:28:02

or sort of spongeability that you take

1:28:05

on so much closes

1:28:07

and we become less plastic

1:28:09

and less able to learn. So yeah,

1:28:12

that critical period plasticity

1:28:15

has been especially well articulated

1:28:18

by Goldaland. And

1:28:20

it very much fits the model, you know, that

1:28:22

psychedelics reopen these

1:28:26

critical periods of plasticity or just

1:28:29

generally open windows of

1:28:31

plasticity.

1:28:33

And then we can work... Has that been tested

1:28:35

with respect to learning of anything,

1:28:37

languages or otherwise?

1:28:39

Not very well in

1:28:41

humans in

1:28:44

terms of learning paradigms and accelerating

1:28:47

learning. We did do one study

1:28:49

with LSD where

1:28:52

we had a certain cognitive

1:28:55

flexibility paradigm where we were able

1:28:57

to look at learning rate, you know,

1:28:59

how quickly you could learn, in this

1:29:02

case, a rule. And

1:29:04

just like the way symbols relate to each other

1:29:06

is quite a sort of low level psychological paradigm.

1:29:09

But we did see that there was an acceleration in learning

1:29:11

rate there. And there should be

1:29:14

more work in that kind of space

1:29:16

than there has been. Yeah,

1:29:18

let's see.

1:29:19

You mentioned microdosing

1:29:22

and passing at some point. Where does

1:29:24

the research stand there?

1:29:26

I remember a study that came out

1:29:28

not long ago suggesting that

1:29:30

it really was some

1:29:32

version of the placebo effect. Yeah.

1:29:35

Yeah, that's another one of ours. Yeah,

1:29:38

so that was Balash Shigeti. And

1:29:42

there we did an interesting

1:29:44

design, a self-blinded

1:29:46

citizen science study. So we

1:29:48

sort of advertised to people, really Balash

1:29:51

led this. And he advertised to people

1:29:53

intending to microdose that,

1:29:55

oh, why don't you get some capsules

1:29:58

and close some entries. T capsules

1:30:00

and do your own blinding

1:30:03

paradigm as if you're running a double blind

1:30:05

randomized control trial.

1:30:07

It was very clever.

1:30:09

Yeah, we got a couple of hundred people to

1:30:11

do it. So the biggest sample I think

1:30:14

to date on microdosing,

1:30:16

it was LSD and mushrooms

1:30:18

you could do either. And there we found

1:30:20

that most of the positive

1:30:22

effects that people were reporting

1:30:26

could be explained by thinking

1:30:28

you were getting a microdose. So

1:30:30

if you got placebo and thought it was a microdose, you did

1:30:32

as well as if you actually got the microdose.

1:30:36

So the evidence is a bit mixed. And

1:30:38

I think the rationale is good and the theory

1:30:40

is good. The low doses of

1:30:42

psychedelics could, in a sense, lubricate

1:30:45

the mind, lubricate the

1:30:47

brain, open a bit of plasticity

1:30:50

without necessarily having a big trip. And maybe

1:30:52

you could do something with that window

1:30:54

of opportunity, that window of plasticity. Problem

1:30:57

is, it hasn't been good enough research

1:30:59

done yet. It's hard to do microdosing

1:31:02

studies because

1:31:04

by definition, it's a dosing

1:31:07

regimen. So you're gonna be doing a lot of

1:31:09

dosing. And are the

1:31:11

ethics boards, the IRBs, gonna

1:31:14

allow you to give participants

1:31:16

psychedelics to take home to do this? Probably

1:31:19

not. So then you have to do it in a lab.

1:31:21

And the typical protocol with microdosing

1:31:24

is a few weeks of sort of one

1:31:26

day on, one day off, or some

1:31:29

variation on that. So

1:31:31

that's a lot of visits and that's

1:31:33

gonna be horribly expensive.

1:31:36

And it's these kind of practical

1:31:39

challenges that have meant that we

1:31:41

haven't done very good microdosing studies.

1:31:44

And when the control studies have been done,

1:31:46

they haven't really come through with compelling

1:31:49

evidence. So I would just say, watch

1:31:51

this space on microdosing. It's

1:31:54

an idea, it's quite interesting,

1:31:56

if not even compelling, but the

1:31:58

evidence isn't there yet.

1:32:00

Well, another reason to fund

1:32:02

some research. Do

1:32:04

you know, Sam, I would like to ask

1:32:06

you

1:32:07

your

1:32:08

understanding of religion and

1:32:11

religion

1:32:13

before it was even organized religion,

1:32:17

the ability

1:32:18

of these religious leaders

1:32:21

to

1:32:22

seemingly tap into

1:32:25

what

1:32:26

we experience in the psychedelic

1:32:29

space

1:32:30

of this

1:32:32

feeling of

1:32:34

unity with

1:32:36

everybody and everything

1:32:36

in the universe as if it's in

1:32:39

form of some religions would call it God

1:32:42

and that boundary between

1:32:44

the spiritual slash metaphysical

1:32:48

and the biological, you know, the

1:32:50

chemistry, the biochemistry, the physics that's

1:32:52

happening in our brains. And

1:32:55

I'm guessing you've considered

1:32:57

this quite a bit. And I just wondered if you would

1:33:00

share. Yeah,

1:33:01

I talk about it a lot, especially

1:33:04

over waking up the our meditation

1:33:07

app. I made the very

1:33:09

big question. I think there's a

1:33:11

few

1:33:12

high level things I would

1:33:14

demarcate. I mean, one is I think,

1:33:16

you know, I have been for many years

1:33:18

now, a fairly vociferous critic

1:33:21

of organized religion, not because

1:33:23

I don't think the core

1:33:25

experiences that lie at

1:33:27

the founding of all or most of our

1:33:29

religions are valid and interesting

1:33:32

and worth having and exploring and

1:33:34

understanding.

1:33:35

But because I think

1:33:37

they are so important and interesting,

1:33:39

and we obviously need a 21st century,

1:33:42

truly non-denominational,

1:33:44

non-sectarian, non-divisive,

1:33:47

not irrational framing of those experiences.

1:33:50

So the reason why I want to get out of the religion business is

1:33:53

because I think

1:33:54

these mutually incompatible claims of

1:33:56

our various Iron

1:33:59

Age and

1:33:59

evil religions

1:34:02

just are blocking a more sophisticated

1:34:04

and useful and not

1:34:06

divisive conversation that's possible.

1:34:09

So insofar as I

1:34:11

can help inspire that conversation, I've been

1:34:13

trying to do that. And in various

1:34:15

moments, my criticism of organized

1:34:18

religion has been fairly denigrating,

1:34:21

but I'm also realistic that I don't think

1:34:23

I'm going to live to see a day where there are no

1:34:25

longer Christians, Muslims, Jews, Buddhists, Hindus,

1:34:28

all vying for recognition of the unique

1:34:30

veracity of each of their faiths. And

1:34:33

I also, I just think we're

1:34:35

in very different lanes here. I think I would just

1:34:38

do nothing but celebrate the fact that you

1:34:40

could reach out to a fundamentalist Christian

1:34:43

and

1:34:43

convince them

1:34:45

that they want to support the

1:34:47

Treat Initiative very much within the context

1:34:50

of their Christianity. I

1:34:52

don't think you should be in the business of

1:34:54

pointing out what is wrong with Christianity. That's

1:34:57

my job. But... Can

1:35:00

I

1:35:01

share with you? Can I share with you real

1:35:03

quick? Yeah, go first. The first, I

1:35:05

had submitted the legislation, I think

1:35:07

it was July 17th, and putting in long

1:35:09

hours and at the end of the

1:35:12

night, there was a voice

1:35:14

memo.

1:35:15

And I debated whether I wanted to listen

1:35:17

to it or not, because if it was something that

1:35:19

might upset me, it might upset my sleep.

1:35:21

But for some reason, I decided to

1:35:23

listen to it. And I wanted to share this with you because

1:35:26

I think it's just jaw-dropping, remarkable

1:35:28

to me.

1:35:29

It was from a very conservative

1:35:32

Christian white man

1:35:34

who said, I read your legislation,

1:35:36

and

1:35:37

I think it's the most impactful and

1:35:39

important legislation I've ever read.

1:35:41

And he said, and I'm

1:35:43

a conservative white Christian

1:35:45

and we get a bad rap these

1:35:48

days. But I want

1:35:50

you to know we're not all bad and

1:35:52

I support you 100%. So of

1:35:54

course I called him later and asked him if he could post it

1:35:57

on our website. So I didn't mean

1:35:59

to interrupt. it just, it was

1:36:01

just further affirmation that this

1:36:03

goes beyond politics

1:36:06

and religion and that there's so much suffering

1:36:08

out there that people are

1:36:10

starving for a new solution.

1:36:13

Yeah. Yeah. Well, what it promises

1:36:16

to me is something like

1:36:18

a 21st century version

1:36:21

of a new mysteries

1:36:23

of Eleusis. This is

1:36:25

the secretive right that was at

1:36:29

the foundation of a fair amount

1:36:31

of Greek philosophy,

1:36:33

but by its very

1:36:35

nature, it was organized, it was

1:36:38

orderly, it was not a matter of

1:36:41

handing out these compounds to

1:36:43

everyone to use recreationally.

1:36:45

I'm very supportive

1:36:48

of decriminalization, but I'm

1:36:50

also very supportive of

1:36:52

circumspection and how we move

1:36:54

into this space.

1:36:56

I say that it is a fair

1:36:59

amount of

1:37:00

apparent hypocrisy to untangle here

1:37:02

because my own

1:37:03

personal and illegal use

1:37:05

of these compounds was absolutely

1:37:07

indispensable back in the day. It

1:37:10

really got me started in

1:37:12

thinking about all of these things. I really

1:37:15

don't think I would have become interested

1:37:17

in the nature of the mind and the

1:37:19

contemplative life. I just think I was a hard enough

1:37:22

case when I was an 18

1:37:23

year old undergraduate in college

1:37:26

that I just, if you had taught me to meditate

1:37:28

at that point, I

1:37:29

think I just would have bounced off the

1:37:31

whole project. So I just think

1:37:35

we as a culture,

1:37:37

as

1:37:38

much as I want to get out of the religion business

1:37:40

and get past all of the political

1:37:43

liabilities of that as I see them

1:37:45

and the unscientific bias that I think

1:37:48

is built into it, I think secular

1:37:50

culture is really starving

1:37:53

for a fully wise

1:37:56

language by which to organize

1:37:59

our lives.

1:38:00

So we have to make the best uses of

1:38:03

all of the human conversations that have preceded

1:38:05

this moment. I think we should grab

1:38:08

everything that's useful in religion and philosophy

1:38:11

and literature and art and every other

1:38:13

corner of discourse,

1:38:15

but I just think we have to recognize

1:38:17

that

1:38:18

what we have in each moment going forward

1:38:20

personally and collectively is

1:38:23

consciousness and its contents and

1:38:25

our only dimly emerging

1:38:28

understanding of how anything that

1:38:30

seems to be happening is happening in the

1:38:32

first place and science remains

1:38:35

the leading edge of that understanding

1:38:38

and what we need is a really rich first person

1:38:43

side of that inquiry and

1:38:46

the introduction of psychedelics into the conversation

1:38:48

puts the furthest reaches of

1:38:51

human well-being and insight into

1:38:54

reach for normal people.

1:38:56

I mean this is, you know, normally you would have to

1:38:58

be the kind of person who would be willing

1:39:00

to spend a year on silent retreat,

1:39:02

you know, to begin to touch

1:39:05

what someone can touch in

1:39:08

four hours under proper guidance

1:39:10

given a compound like MDMA

1:39:12

or psilocybin

1:39:13

and so it's not

1:39:16

to say that there aren't differences between meditation

1:39:18

and psychedelics. I've talked about those in other

1:39:21

contexts but there's a fair amount of

1:39:23

overlap there as well and so I just think it's

1:39:26

fantastic what you guys are doing

1:39:28

and I really appreciate you both coming

1:39:30

on the podcast to talk about it.

1:39:32

Well thank you and

1:39:33

just a quick shout out to Brian

1:39:35

for his book The Immortality Key. Yeah.

1:39:38

Where he's just a brilliant

1:39:40