0:05

This podcast is supported by Americans for Medical

0:07

Progress and was founded and created through the Michael

0:09

D Hare Fellowship , awarded annually

0:12

to support projects that inform and educate the public

0:14

about the critical role of animal research

0:16

in furthering medical progress . The Fellowship

0:18

honors the late Dr Michael Hare , a renowned

0:21

board-certified laboratory animal veterinarian

0:23

who dedicated his career to scientific

0:25

and medical advancements and who was deeply committed

0:27

to animal welfare and advocacy . Hey

0:42

everyone , and welcome in to this month's

0:44

edition of Labrat Chat . Thanks

0:46

for joining us and , as always , please

0:48

take a second pause . If you can

0:50

go into Spotify , press

0:52

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0:54

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1:09

again , our email . If you ever have , you know , suggestions

1:12

, comments , just for us personally , danielle and I will

1:14

respond to them labratchat at gmailcom . So

1:17

thanks everyone again for

1:19

tuning in . Today we

1:21

have an exciting guest . His

1:23

name is Dr Alejandro Tirado-Pacheco

1:26

. He's from Oregon Health Sciences University

1:28

. He's a postdoc up there , a

1:31

lab that focuses on want to know

1:33

if the lab focuses on it . But what we're talking to

1:35

him today about is the

1:37

use of kind of psychedelics

1:39

and how that can benefit mental health

1:42

. Especially with the last month , may , being mental

1:44

health awareness month , we thought it'd be

1:46

a cool idea to actually talk

1:48

to someone that does research in that

1:50

field and how it can possibly benefit

1:52

us and how the use of animals help , you know

1:54

, accomplish that goal . So , if you will , dr

1:57

Tirado-Pacheco , just tell us a little bit . You

1:59

know about yourself . We got you interested

2:01

in science and research and then

2:03

in this kind of field , particularly

2:06

if you would just tell us a little bit about

2:08

that .

2:09

Yeah , well , first of all , thanks a lot for

2:11

having me on . It's really exciting to be able to talk

2:13

to the public about this research . I

2:15

don't get the chance to do that a lot , so I'm really

2:17

really glad to be here . So I guess , yeah

2:19

, my story is a bit of a bit

2:22

of a wandering path to get to where I am

2:24

today . I grew up in Europe and

2:26

I was really into science from a young age and

2:28

the system , the way it works in Britain

2:30

, which is where I went to university , is that you apply to university

2:33

when you're very young , like 16 , 17

2:35

, and you don't have a major . You just apply

2:37

for something . And so I applied for a physics

2:39

program and you go in and you

2:41

only do that . So I started this physics

2:43

program and two years in I

2:45

was basically ready to quit because

2:48

you know , as you can imagine , choosing

2:50

a career when you're 17 years old , the chances

2:52

that that works out are pretty slim . But

2:55

then I got introduced to these ideas

2:57

about graph theory and dynamical

2:59

systems , so all these like mathematical

3:01

methods that you could use to model things

3:03

in the world . The problem

3:05

I had with physics was it was too abstract . I couldn't

3:08

really relate what was going on in the math

3:10

to the real world . But when I

3:12

got introduced to these ideas and especially to the fact

3:14

that you can model something like the brain using

3:17

these mathematical tools , that was really fascinating

3:19

right , that you can use these tools to think

3:21

about cognition , behavior and even

3:24

emotion , and so that was kind of my entry point

3:26

into neuroscience . So I

3:28

did a computational neuroscience master's

3:31

at University College London

3:33

And it was actually a physics master's

3:35

, but I did a computational neuroscience thesis in

3:38

a lab over there , peter Latham's lab

3:40

And I decided I would go to grad

3:42

school for neuroscience . And so I ended up

3:44

going to Brandeis University , which is

3:46

in Massachusetts , for my PhD . And

3:49

that was another choice that was dictated by the difference

3:51

which might be interesting to your listeners , differences

3:53

between the European and the American system

3:55

. In the American system you come into grad

3:58

school and you have a couple of years of classes

4:00

and you get to sort of explore

4:03

different labs and then choose what you're going

4:05

to do . In a lot of places in Europe , the way

4:07

it works , you as you find a professor

4:09

and you sort of ask them

4:11

. You know I would like to work with you on this

4:13

topic , so you have to really have a good idea of what you

4:15

want to do . But because I came in from the

4:17

sides basically and you know I didn't have

4:19

any biology background , i applied

4:22

only to the US because I wanted that

4:24

opportunity to explore different topics

4:26

And I thought I was going to do computational neuroscience

4:28

but I ended up falling in love with

4:31

experiments , especially experiments

4:33

with freely behaving animals . I just love

4:35

the techniques and what you can learn from those . So

4:38

I joined Gina Torrigiano's

4:40

lab at Brandeis . Over there I studied

4:42

sleep and plasticity , so how brain

4:45

plasticity is affected by sleep . So

4:47

, as you can see , kind of none of this has anything

4:49

to do with mental health or psychedelics

4:51

, but the way I thought about it , i always wanted

4:53

to work with psychiatric disorders And the way I thought

4:55

about it was my PhD was an opportunity to

4:57

learn neuroscience and

4:59

learn techniques and then apply those

5:01

later on in the next step , and

5:04

so that's what I'm doing now . Like you said in

5:06

your introduction , i am a postdoc in Bita

5:08

Mogadam's lab in the Behavioral Neuroscience

5:10

Department , ohsu . What we're

5:13

studying is broadly . The lab

5:15

is interested in the neurobiology of

5:17

psychiatric illnesses . Bita

5:19

has , you know , 30 years of experience working

5:22

in this field and she's done a lot of work

5:24

with schizophrenia , and when

5:26

I contacted her about working in her

5:28

lab , she offered me this project

5:30

that she was interested in to pursue research

5:32

on psychedelics and especially psilocybin

5:34

, because of the really promising

5:36

data in humans , and we can talk about that later

5:38

. But yeah , so now that's what I'm studying , looking

5:41

at psilocybin and major depressive

5:43

disorder .

5:44

Yeah , it's crazy that you apply to a university when you're 16

5:46

, 17 , and you have to pick what you want to do . I

5:48

mean , it's kind of similar , i guess , in a way , in

5:50

the American system You go

5:52

to college when you're 18 . And if you have a scholarship

5:55

I think a lot of scholarships , state-sponsored scholarships

5:57

require you to pick a major by

5:59

the end of your first semester or first

6:02

year or something in order to keep your scholarship . And

6:04

so even then , like 18 , 19 , you

6:06

don't know what you wanted . It took me , i mean , look , i went back

6:08

to school at 32 . So

6:10

I didn't know . It took me a while to like actually

6:12

get into a career or some

6:14

sort of job that I was interested

6:16

in and then to explore that further , so

6:19

then break it down and figure out what I really wanted to

6:21

do within that field . And so it's kind

6:23

of crazy that at 16 , 17 , that

6:25

you're forced to try to make that decision .

6:28

Yeah , it's pretty wild . And the thing is

6:30

there's no major or minor , so you just

6:32

go in , and so I took no college

6:34

level classes in biology , chemistry

6:36

, anything else . That wasn't even science

6:39

, like just physics . So I really think

6:41

it's limiting .

6:42

I don't know . that sounds kind of nice , though I just remember in my

6:44

undergrad having to take like sociology

6:47

and Greek mythology and you're just like I

6:49

don't want to learn this . This is so far better

6:51

.

6:51

Greek mythology is pretty cool . I like Greek mythology

6:53

. I took it because I thought it would be cool . It's

6:55

not cool , it's not when you have to write a paper , yeah

6:57

right , when you have to write a five-page paper .

6:58

I immediately regretted that decision . But

7:00

I have a quick question just about , like

7:03

, what psychedelics are , because when I think

7:05

about that I think of mushrooms . So I'm sure , well

7:07

I don't know . Are there other means

7:09

of where the compounds come from ? I guess , what

7:11

exactly is psilocybin , some of the

7:13

other psychedelic compounds that you work with ? where do

7:15

they come from ? How do you even obtain

7:17

them ? Well , i imagine they're like controlled

7:20

substances , but maybe you could just talk a little bit about

7:22

the compounds themselves .

7:24

Sure , i guess I'll start with what they are

7:26

. There's three main classes of

7:28

psychedelics and they're just like , biochemically

7:31

slightly different , but I'm not a biochemist

7:33

myself , so those things don't really mean much to me

7:35

. But essentially all of them are very closely

7:37

related to serotonin and

7:40

they act on serotonin receptors

7:42

in the brain . And then they have slightly different pharmacological

7:45

profiles . You know , some are natural

7:47

compounds , like psilocybin , like

7:49

you mentioned , is found in mushrooms . Another very

7:51

popular one is DMT , or dimethyl

7:54

tryptamine , which is found in

7:56

some species of toads and in some

7:58

plants as well . And then a lot of them

8:00

are just synthetic compounds , for example

8:02

LSD , the most famous one of them

8:04

all . So the interesting thing is a

8:06

lot of them are controlled substances

8:09

and they are like at the highest level , So

8:11

they're schedule one substances . So psilocybin

8:13

is schedule one , lsd is schedule one , and

8:16

so , yeah , it takes a while to get them

8:18

. You have to have a license with a DEA

8:20

Luckily I don't , but my boss does And

8:23

it takes a long time to get that and then

8:25

it takes a long time to get the compound . The

8:27

National Institutes of Health has a drug supply

8:29

program through the National Institute

8:31

on Drug Abuse . So basically the

8:34

idea is we want to study these

8:36

quote-unquote drugs of abuse to

8:38

understand them better . They can give you small

8:40

amounts of these drugs when you request them . There's

8:42

a lot of paperwork involved and you have to obviously justify

8:44

why you want it , what you're

8:47

going to do with it and how this is going to benefit

8:49

the public . There are other compounds

8:51

that are actually not scheduled , even though they're

8:53

extremely similar . So one of them is DOI

8:56

, and if you look up psychedelic research , you'll

8:58

see this DOI pop up all the

9:00

time , and that's because you can just buy it , and so

9:02

I don't know what it feels like to take it . I don't

9:04

know how similar it is to LSD or psilocybin

9:07

, but it's freely available and it's kind

9:09

of used as a proxy for psychedelic

9:11

effects . I personally think it's not

9:13

exactly the same , but we can get into that if

9:15

we want to later on .

9:17

Is that also something that comes from mushrooms

9:19

? That's just like a synthetic compound someone's made

9:21

.

9:21

That's synthetic . And actually I should mention

9:23

the psilocybin that we get and that everyone

9:26

gets is at this point synthetic . So it's

9:28

made in a lab , because when

9:30

you extract it from mushrooms you get a lot

9:33

of impurities .

9:34

Okay , So it's a process of extraction

9:36

. You can't go out and just find the mushroom

9:38

and eat it and get the psilocybin effects

9:41

. It's kind of like , I don't know , I guess like cocaine

9:43

. If you will , You got like there's a process to make it into

9:45

cocaine And I guess there's a process to make

9:47

psilocybin . I'm not trying to give information on how to

9:50

make it , or process it .

9:51

You're teaching people how to do that .

9:52

Well , my biochemistry book in school detailed

9:55

the process of how to make crack

9:57

detailed . Oh my gosh that's hilarious . It's

9:59

like the protocol on how to do it Probably

10:01

no longer in publication And I didn't try it

10:03

just for the record .

10:04

Either way , people should not go out and just eat mushrooms

10:07

, because you have no idea .

10:08

Yeah . So I guess if they're scheduled one drugs

10:10

, if it's something that you could just go out and

10:12

get in nature , or if it takes a pretty

10:14

like advanced process to actually get

10:16

the compound out of it , You know

10:18

, for lab research we want to make sure it's a

10:20

pure compound , so we use the synthetic version

10:23

.

10:23

But yeah , it's naturally available . And I should mention you

10:25

know it's been used for millennia by people

10:27

all over the world , especially in

10:29

what is currently Mexico . So in

10:31

Mesoamerica people have been using

10:34

psychedelic mushrooms for religious

10:36

and other important cultural ceremonies for

10:38

a long , long time .

10:40

Good to know . It seems like

10:42

there's definitely a lot of positive use

10:44

for it . I think it seems like when I was a kid

10:46

I remember talks about mushrooms

10:48

and how people would hallucinate

10:51

. I just remember conversations about if you

10:53

took them you're going to hallucinate and go jump off a building

10:55

and all the side effects and how awful they are

10:57

and how they need to be banned from society

10:59

. But now it's nice that there's kind of maybe

11:01

the little bit of shift coming on in society

11:04

and finding a positive use

11:06

for it . And I think in order to get to that understanding

11:09

, research needs to be done , and I think that's kind of where

11:11

you guys come in . I know there's lots

11:13

of human research in there out there as well

11:15

, but in order to really get a good understanding

11:17

, i think it's important that we do some of the

11:19

animal research . So if you would

11:21

, can you just tell us a little bit about your research

11:24

? Which animal model do you guys use

11:26

once you get that synthetic psilocybin

11:28

compound In order to study

11:30

it ? you've had a lot of findings , but what's

11:33

like a broad spectrum approach

11:35

to some of the findings that you've been

11:37

able to discover using that animal model ?

11:40

Yeah . So we use rats in the lab

11:42

and there's a very specific reason

11:44

, and the reason is that we are interested in

11:46

the behavioral effects of psilocybin

11:49

. So I'm going to back up a little and tell

11:51

you a bit about the human data , because that will kind of bring it

11:53

into context why we're doing what we're

11:55

doing . There's a lot of phase one clinical

11:57

trials and even a few phase two clinical

11:59

trials that show incredibly promising

12:02

results for psilocybin . And to kind

12:04

of tell you what that means , incredibly promising

12:06

. I'm talking about two doses

12:08

of psilocybin three weeks apart having

12:10

a stronger effect in ameliorating

12:13

symptoms of depression than a

12:16

six-week course of a standard medication

12:18

, which would be a selective serotonin reuptake inhibitor

12:20

, you know , like prozac or lexapro . That's crazy

12:23

, it's very striking , it's

12:25

fast-acting and it's long-lasting . So

12:27

people have looked up to six months after

12:29

one or two doses and you still see

12:31

an effect . Yeah , that's incredible

12:34

. And it's really important to sort of

12:36

underscore the fact that , while

12:38

accessorizer are amazing and I can

12:40

probably say that they've saved countless

12:42

lives They have a lot of side effects and

12:44

adverse effects and you know people

12:46

end up having to take this medication every day

12:48

. So it's you know you get sort of problems with people

12:50

taking it . We've been on the hunt for

12:53

a better treatment for depression

12:55

for six decades or so , so

12:57

it's really cool that we now have a few options like

12:59

ketamine is one , and now psychedelics are emerging

13:01

as a really promising option .

13:03

Ketamine- is one I didn't know that Yeah , we

13:05

use ketamine all the time . I don't know it was used in

13:07

the mental health realms . I thought

13:10

it was more just in the realm of like just an addictive

13:12

kind of like cocaine , heroin

13:14

type of drug . But I guess it has use as

13:16

well . I know that's not the focus of your research

13:18

, but that's just not that interesting .

13:20

Yeah yeah , ketamine is interesting because

13:22

the different doses do very different things . So

13:24

at high doses it's an anesthetic I know

13:26

it's used in animals for anesthesia

13:28

but at low doses it has

13:31

this weird antidepressant effect

13:33

, and so it's actually pretty close to FDA

13:35

approval , i think Awesome .

13:37

Okay , that's cool . Yeah , i mean , we use it quite a

13:39

bit and cats that want to try to kill us while

13:41

at work , when they're hissing at you , you can score

13:43

a little bit in the mouth . It calms them down

13:46

a little and they do a little anesthetic properties

13:48

, like you said . But yeah , that's cool , good to

13:50

know as well .

13:51

Yeah , so going back to I guess the reason

13:53

I talked about all that is because psychedelics

13:56

have an interesting history . You know they were

13:58

used in the 50s and 60s in research

14:00

. Then they you know research stopped because

14:02

the control substances act made them

14:04

schedule one substances . And now we have all

14:07

this human data , but we have a real gap of

14:09

knowledge in terms of the biological mechanism

14:11

, and that's where the animal research comes

14:13

in . We want to understand why are

14:16

they so effective ? right , what is happening

14:18

in the brain when you take psilocybin

14:20

, and you know later on you feel better . And

14:23

so to do that , we have to be able to

14:25

see an effect . Is the animal actually

14:27

feeling psilocybin and perhaps does

14:29

it have an antidepressant like effect ? and

14:31

then what is happening in the brain ? So we have to be able to

14:33

use techniques that

14:36

you wouldn't be able to use in humans , that are

14:38

invasive , that you can do in animals . And

14:40

so in our research , what we really sort

14:43

of noticed is that in the polyclinical trials

14:45

you know you might have heard this phrase set

14:47

and setting in terms of psychedelic use , where

14:49

you know the mental set , so your expectations

14:52

coming in your current mood , your history

14:54

, your genetics , that plays a part , and

14:56

also the environment plays a part , right , so

14:58

you're the peers who is present

15:00

during that experience , the kind of support

15:02

you have , even just the physical

15:04

environment . All of that really affects

15:07

the experience and the outcome . And

15:09

so in these clinical trials people are

15:11

usually in a very , very safe feeling

15:13

environment . They're usually on a bed with relaxing

15:16

music and sometimes eye shades

15:18

, and there's usually two support

15:20

staff who are often trained

15:22

psychologists or therapists , and

15:25

the idea is not to give , like it's non-directive

15:27

, supportive therapies , what they call it , so it's not really

15:29

like therapy session , but there is that

15:32

sort of support . And so we thought maybe

15:34

what's happening is that the effect

15:36

of psilocybin is to sort of prime

15:38

people to get the most out of that

15:40

experience , and so really the effects while

15:43

the drug is on board are important

15:45

to study . We decided to do that

15:47

in rats And broadly what we found is

15:49

that , very surprisingly , rats

15:51

can be better at some tasks

15:53

that require cognitive flexibility

15:56

, so the ability to switch between

15:58

different behavioral strategies depending

16:00

on the environment , while they

16:03

are essentially high on psilocybin . And

16:05

you might ask , what does that have to do with depression

16:07

, what you've been talking about ? Well , cognitive

16:09

flexibility first of all , is associated with

16:12

greater mental health . Cognitive

16:14

inflexibility , so kind of rigid thinking

16:16

and rigid patterns of behavior

16:18

, are seen in a lot of psychiatric

16:21

disorders , including depression and

16:23

anxiety disorders , and higher

16:25

cognitive flexibility , which is measured

16:27

in humans with tasks very similar to the ones we

16:29

use in rodents , is associated with greater

16:32

mental health and also better responsiveness

16:35

to treatment for depression . So

16:37

there's a very strong link there , and

16:39

basically the idea is that the

16:41

hypothesis that we have , and others that propose as

16:43

well , is that psychedelics promote a

16:45

state of higher flexibility that then

16:47

allows people to break out of

16:49

ingrained patterns of thought , of

16:52

ingrained sort of negative perceptions

16:54

of the self or the environment

16:56

. Our research in animals sort

16:59

of supports that idea And also

17:01

, well , currently and in the near future

17:03

, we're trying to also understand how this is happening

17:05

, so that we can first of all get

17:08

an understanding of that process in the brain

17:10

which would be great And also perhaps

17:12

design compounds that can

17:14

better target the specific

17:16

therapeutic action that we're looking for , as

17:18

opposed to something like psilocybin , which is

17:20

perhaps having a lot of effects that are

17:23

maybe undesirable or even just unnecessary

17:25

.

17:26

I have a question about why rats would

17:28

be the best animal for this , Because , now that I'm

17:30

thinking about it , all the places I've worked

17:32

where there is like a psychology department or

17:34

something , it seems like rats are always the go-to model

17:37

And I didn't know if there was a particular reason . Is

17:39

it maybe just because their brains are bigger than mouse

17:41

brains ? or maybe they can learn different

17:43

tasks easier ? But I guess what's the draw

17:45

to rats for this type of work ?

17:47

Yeah , that's a great question , And it really boils down to the

17:49

fact that they're just smarter than mice . This

17:53

is what it is , the task that we use

17:55

. Mice would just not be able to do it .

17:57

Okay , interesting .

17:58

Were you guys planning on using , like higher

18:00

level species , like you plan on going into

18:02

monkeys or something like that to do this

18:05

, or is that something that's not necessary ?

18:07

I think it could be interesting , but our

18:09

lab is not equipped for that . I

18:11

wouldn't be surprised if someone started

18:14

doing research with psychedelics

18:16

and monkeys . I think the things

18:18

you can learn from all the different species

18:20

are a little bit different , you know , and so all

18:22

levels of research are valuable . But

18:24

even in mice people do a lot of research with psychedelics

18:27

and they just look at different things . So

18:29

for us , with the behavioral focus that we have

18:31

, rats are a really optimal choice .

18:33

That kind of lends itself to my next question , because we like

18:35

to ask our guests to kind of get their

18:37

take on this . In your opinion , is there a

18:39

way to conduct this research , or maybe

18:42

preliminary research , using computer

18:44

models or organs on a chip or any

18:46

other alternative , without using animals

18:48

? We just kind of like to get different opinions

18:50

on that .

18:52

I think , for what we are specifically trying

18:54

to do . What we're trying to understand is how

18:56

does the brain produce a certain behavior

18:59

and how does this external agent

19:01

, this drug , change brain activity

19:03

? that then changes the behavior , and so if you

19:05

don't have the behavior part , you're really

19:07

sort of losing a whole level of analysis

19:09

. So I don't think we could do the research we're doing using

19:12

a computer model or a brain in a vat

19:14

. Essentially , that said , i

19:16

think that those types of techniques or those

19:18

types of models are really valuable , because

19:21

our goal with animal research is always

19:23

to keep the number of animals that we're

19:25

using at a minimum . We always want to try

19:27

to minimize the number of animals and that can be done with careful

19:30

study , design and repeated measures

19:32

, designs and stuff . But of course , if

19:34

your question is answerable

19:37

without using an animal , then I

19:39

think it should be , and I think it would

19:41

be really cool to see some psychedelics research

19:43

done in , for example , brain

19:45

organoids , which I don't know maybe for some

19:47

of the listeners who are not familiar , what

19:49

these are is . You can take human

19:51

stem cells and then differentiate

19:54

them into neurons in a dish And it

19:56

becomes essentially a human

19:58

brain in a dish . Obviously it's not a real

20:00

human brain , it's not the same thing , but

20:02

it's been used to study human brain

20:04

development from a genetic standpoint , and

20:06

I think something like that would be great to answer some

20:09

questions about what psychedelics do , for

20:11

example , to specific cell types

20:13

that are found in a human brain but not in the brain

20:15

of a rat .

20:16

I've been asking , speaking about the brain and looking

20:18

at changes in cell type , and maybe you said it and

20:20

I mentioned . But when someone takes psilocybin

20:23

, like in these clinical trials , and then they look

20:25

at the brain , or when you guys are looking at your rats , are there

20:27

permanent changes to the brain

20:29

that psilocybin causes , like give

20:31

the long lasting kind of effects

20:33

that are like ? are they permanent changes

20:36

to the brain or are they just something that they're temporarily

20:38

changes to the brain that alleviate the signs

20:40

of depression , that then eventually

20:43

reverse back to normal cell

20:45

types , or should just have changes to do

20:47

with like synapses or just psilocybin just have like

20:49

a long half life in the body that's causing

20:51

the side effect that we see , if you know , alleviating

20:53

signs of depression .

20:55

Yeah , that's a fantastic question And it's not

20:57

a settled one . There are definitely long

21:00

lasting changes for psilocybin . So one

21:02

of the things that has come up we mentioned

21:04

ketamine before and this is true also for ketamine

21:06

. These compounds cause plasticity

21:09

. They cause growth of synapses

21:11

, essentially in the brain . When people have looked

21:13

and that can be something that's fairly long

21:15

lasting We don't have the data

21:18

to look , let's say a year after administration

21:20

but it does seem to be a persistent increase

21:23

in the potential number of synapses in

21:25

some parts of the brain after psilocybin

21:28

, after ketamine . Whether

21:30

that is directly related to

21:32

the depressive symptoms , it's hard

21:34

to confirm for sure , but that's

21:36

definitely a leading hypothesis about why

21:38

. The other option , which is kind

21:40

of like our angle , is a bit more that

21:42

this plasticity is perhaps a direct

21:44

correlate of the increased flexibility And

21:47

then it's kind of a resetting of the ability

21:49

to make new connections , and so maybe

21:52

you can think of it as rewiring

21:54

your brain in a way . So instead of

21:56

being stuck in this loop of negative self

21:58

perception and perception of the environment , you can

22:00

rewrite all that and come

22:02

to a different state after that experience

22:04

. Perhaps it's not a lasting physical

22:07

state , it's a physical state that lasts

22:10

a little bit and allows you to change

22:12

other things , but it's also possible

22:14

that there are changes that are , for example , gene

22:16

expression , that are very , very long lasting

22:19

, and we just don't know yet . So I would

22:21

say it's an open question , but it's definitely

22:23

something that people are looking into and

22:25

that is a very promising avenue for research

22:27

.

22:28

Yeah , absolutely , and we always

22:30

like to help our listeners kind of understand

22:32

the potential applications of the

22:34

research that you're doing . Maybe

22:36

it's like when we have guests on the show and how

22:38

that's going to affect our society

22:41

, and so you've said a lot already about how I

22:43

think your research has helped advance our understanding

22:45

of the use of these psychedelics , particularly

22:48

psilocybin . Do you think in our

22:50

lifetime even which I mean I think we're

22:52

all relatively young , but do you think

22:54

in our lifetime we're going to see these compounds

22:56

being accepted as a powerful

22:58

therapeutic tool , something that doesn't require

23:01

people suffering from PTSD

23:03

or depression to enroll in a

23:05

clinical trial , like , do you think psychiatrists

23:08

will eventually be able to use it in

23:11

practice , like regularly , outside of

23:13

clinical trials ? That's what I'm getting at , i guess

23:15

.

23:16

I think that's definitely where the momentum

23:18

is going . Here in Oregon , there

23:20

was a ballot question and it ended up

23:22

resulting in the approval of psilocybin

23:25

as a medication . essentially , it's a

23:27

complicated legal and logistical

23:29

framework , but it's definitely going that direction

23:32

. To answer your question of will it happen in

23:34

our lifetime , i think so , but

23:36

I want to be a little bit cautious . There's

23:38

a great paper from a couple of the

23:40

people that have been doing a lot of the clinical trials , like

23:42

Roland Griffith and David Yead . In

23:45

this little , very short paper they talk about the

23:47

bursting of the psychedelic bubble . Their

23:50

idea is when you have something that has so

23:52

much hype behind it , it creates this

23:54

bubble of expectations . It's kind of like you

23:56

get sensationalists , news articles

23:58

and this is the miracle cure for everything

24:00

and it's going to cure depression for everybody

24:02

. It's our role as scientists

24:04

to be realistic and cautious and

24:06

to not feed into that , because

24:08

what can happen is that you then get a

24:11

pushback when all

24:13

these incredibly high expectations don't materialize

24:15

and then you get very negative coverage

24:18

and very negative landscape for funding

24:20

and for continuing to do this research . This

24:23

is kind of what happened in the 50s and 60s

24:25

. People were so had such

24:27

high expectations on these compounds , which

24:29

were not illegal at the time , that they first

24:31

of all promoted them as they were going to be the cure-all

24:33

for the world and for

24:36

all the ailments in the world . But also

24:38

they did very , very sloppy research and

24:40

that , combined with popular culture , the

24:43

use of these compounds , but definitely the poor

24:45

research , contributed to these

24:47

substances being kind of written off the map

24:49

of research for several decades with

24:51

the Control Substances Act of 1970 . And

24:53

so I think it's important to be cautious about

24:55

our expectations . It's unlikely that

24:57

we're going to ever find a complete

25:00

cure , pharmacological cure , for depression

25:02

. That said , the more tools we

25:05

have in our toolbox , the better . I

25:07

really think that psychedelics are going to be one of

25:09

those tools , and it will take time . Ketamine

25:12

has had kind of a similar progression and it's taken

25:14

more than 20 years to go from the first

25:16

promising research to almost

25:18

FDA approval and there are actually ketamine clinics out

25:20

there . So I think it will happen and

25:22

hopefully we can sort of temper

25:24

expectations and be

25:26

careful with our research and really get these

25:29

compounds accepted as what

25:31

they are , which is another potential

25:33

tool in treating these disorders that are

25:35

very , very hard to treat and that really affect

25:37

people's lives .

25:38

But yeah , i hope that made sense Makes perfect

25:40

sense , and I think it's important too that

25:42

if they do become more widely accepted

25:45

and are able to start being used , that

25:47

they have to be used correctly , right ? Because you talked

25:49

about some of the negative side effects , but we didn't really talk

25:51

about what the negative side effects were , and

25:53

if people were using them irresponsibly or at

25:55

higher doses that were too high

25:57

for the human body to handle , then

26:00

they could have obviously very negative consequences

26:02

as well , right ?

26:04

Of course , safety is a big concern

26:06

with these things . I don't think it's ever going to be

26:08

the kind of medication that your doctor hands you , the

26:10

prescriptions like , yeah , one type

26:13

of acid every three weeks . that's

26:15

just not how it's going to work . More

26:17

likely than not it's going to be the way the clinical

26:20

trials have been done . So there's a preparatory

26:22

sessions and there's a very specific

26:24

sort of protocol for having the

26:26

experience with psychological

26:28

support , and then a debriefing session

26:30

and then another experience . You know it's

26:32

all very , very standardized and

26:35

the support is essential . So I think

26:37

that's probably how it's going to go . And yet

26:39

, when done that way , the adverse

26:41

effects and side effects are actually very

26:43

minimal . That's a good thing , yeah

26:45

, absolutely .

26:47

One question that we always like to ask our guests , and

26:49

I think you might have an interesting answer

26:51

, just based on your unique research

26:53

. How do you go about describing

26:55

to strangers what you do for a living , so

26:58

like if you're at a party or trapped

27:00

on an airplane next to someone like , how

27:02

do you bring up that you work with research

27:04

, animals and , on top of that , psychedelics

27:06

. It's kind of a unique combination .

27:09

It's funny because the psychedelics part

27:11

most people think , oh wow , that's so

27:13

cool , so that part is easy . And

27:16

then , yeah , the animal part is . I

27:18

recognize that it's a difficult sort of a delicate

27:20

subject for some people , and so you know , i've

27:22

asked people how they feel about animal research

27:24

, because it's kind of a sensitive subject , and

27:27

, interestingly , most of the time the response

27:29

I get from just people who are not scientists

27:31

at all . It's kind of the same thing that I feel

27:34

, which is that we're making this sort of ethical

27:36

bargain where animal research

27:38

is necessary because we

27:41

are trying to alleviate suffering

27:43

and trying to come up with treatments

27:45

for all these different disorders , And

27:47

even at a basic science level , we need to understand

27:50

the biology to be able to get back

27:52

to the translational level . I

27:55

feel like everyone has an understanding of that intuitively

27:58

. It makes it a little

28:00

bit easier to talk about that , but I find that people

28:02

don't actually , while they have this understanding

28:04

, they don't really know in practice

28:06

what that looks like , and so I'd really try

28:09

to make the point that we obviously try to

28:11

do this , while we do everything in the most humane

28:13

way possible . We have very standardized

28:15

protocols that are checked by veterinarians

28:17

, we use sterile

28:19

technique and anesthesia and all this when we

28:21

do surgeries on our animals , for example . But

28:24

also we try to minimize animal use . So

28:26

we can use statistical analysis and

28:28

careful study design And

28:31

, like you said , potentially alternative model

28:33

organisms or even computer modeling to

28:35

minimize how many animals we use And

28:37

so kind of trying to make the point that we understand

28:39

we're trying to do this in the most ethical

28:42

way possible . I feel like people are really

28:44

receptive and interested when they

28:46

actually learn how it happens in practice .

28:48

Yeah , absolutely , and that's great that

28:50

you make that point to kind of explain all that , because

28:53

once I mean , of course , like you said , try to minimize

28:55

the use , it'd be great not to have to use animals

28:57

, but unfortunately we still need

28:59

those animals to make discoveries that

29:02

are going to benefit both humans and animals . And

29:04

taking the time to explain it I think helps , because

29:06

99% of us have never

29:09

been inside of an animal or

29:11

a research laboratory and seen kind of how

29:13

it goes down or been a part of an eye-cook meeting and

29:15

hear the discussions that they have and how it's all

29:17

about . You have to have humane endpoints to ensure

29:20

they're not suffering and yada-yada . We've had

29:22

the whole eye-cook discussion down here before

29:24

about protocol breakdown and what goes into the protocols

29:26

. So if you want more information on the

29:28

approval process and how that goes , you can go back

29:31

to one of our earlier episodes and hear all of that

29:33

. But it's great that you take the time to do that

29:35

Before we wrap up this episode . Do you

29:37

have any other final statements or thoughts

29:39

about anything that we haven't covered

29:41

or anything you want to reiterate , just

29:43

kind of either whether or not it's about just

29:46

the animal research side of things or about your research

29:48

, or about the use of psychedelics or any other

29:50

topic .

29:51

And , sir , you gave me that opportunity . I would like to make a couple

29:53

points , if I may . One of them is related to your last question

29:56

and it's something I wanted to mention that I

29:58

forgot . I really want to make the point that

30:00

as scientists , we are accountable to

30:02

the public , because most of

30:04

the time , we are funded by taxpayer

30:06

dollars , and so I really appreciate

30:08

what you guys are doing here , and because

30:10

we want the public to see the value of

30:13

animal research , i want people to see the value

30:15

of the research that they're funding and get people behind

30:17

funding for translational and basic science

30:20

, and so thanks for doing this And

30:22

, yeah , i think that's an important part of science

30:24

. Communication is to really make that point

30:26

. And then the other thing I wanted to say is

30:28

that if you're interested in psychedelic

30:30

research , i really would like to

30:32

recommend the MAPS organization

30:34

. So MAPS is the Multidisciplinary Association

30:37

for Psychedelic Science , and they are sort of

30:39

a broad consortium of scientists and

30:41

people who work in field who are conducting a lot

30:43

of the clinical trials . I'm not part of them , but

30:45

I think it's a great thing to look in terms

30:48

of seeing what psychedelic research is about

30:50

, and so if you want to check them out there at mapsorg

30:52

and they're been actually behind

30:54

a lot of the trials with MDMA which we

30:57

haven't talked about but which will very likely

30:59

be approved as a treatment for PTSD

31:01

. So I just wanted to give a shout out to them . Oh

31:03

and sorry . One more thing , if you want to check us out

31:05

our lab is you can look up the Moga

31:07

Down Lab at OHSU .

31:09

We really appreciate your time . I've learned a lot

31:11

. I think all of our listeners have probably learned a lot after

31:13

listening to this whole episode . So

31:16

thank you for you being willing to come on

31:18

and talk to us and break all this

31:20

down . For us And it's , like we

31:22

said , kind of a topic that doesn't seem to be

31:24

discussed a whole lot , but hopefully we start hearing

31:26

more about it , because anything we can do to help benefit

31:29

mental health and especially depression

31:31

and PTSD and all that If we can do anything

31:33

to help those people suffering from that , it's

31:35

fantastic . So thank you for everything that you're

31:37

doing and thank you for taking the time to talk

31:40

to us today . We truly appreciate it .

31:42

Thanks so much , it was my pleasure .

31:44

Absolutely . Thanks , guys . Thanks , be

31:47

sure to go write review our show again If you're still

31:49

listening . Hopefully you made it this far . Write

31:51

review us . It does help us and we will

31:53

catch everyone next time . Thanks everyone .