Speaker 1: Hi, I'm Ethan Nadelman, and this is Psychoactive, a production
Speaker 1: of I Heart Radio and Protozoa Pictures. Psychoactive is the
Speaker 1: show where we talk about all things drugs. But any
Speaker 1: of views expressed here do not represent those of I
Speaker 1: Heart Media, Protozoa Pictures, or their executives and employees. Indeed, heed,
Speaker 1: as an inveterate contrarian, I can tell you they may
Speaker 1: not even represent my own. And nothing contained in this
Speaker 1: show should be used as medical advice or encouragement to
Speaker 1: use any type of drug. Hello, Psychoactive listeners. So today
Speaker 1: we're gonna venture into a territory which I rarely or
Speaker 1: ever enter into, which is the neuroscience of drugs. You know,
Speaker 1: I'm I'm always drawn to the history, the culture, the politics,
Speaker 1: what have you, the therapeutic side, but it's important to
Speaker 1: try to get a sense of why some drugs work
Speaker 1: the way they do, and in this case, we're going
Speaker 1: to focus on why m D M A and psychedelics
Speaker 1: seem to have this remarkable therapeutic potential, which is kind
Speaker 1: of sort of what's behind this psychedelic renaissance. The person
Speaker 1: I've asked to join me today to talk about This
Speaker 1: is Professor goul Dolin. She's in the Department of Neuroscience
Speaker 1: at Johns Hopkins Glula Medicine. She's been doing research on
Speaker 1: psycholics in recent years, but she's got a much longer
Speaker 1: background going to doing research on oxytocin and try to
Speaker 1: understand autism better. She got her m d and her
Speaker 1: PhD at Brown and m I T. She did a
Speaker 1: post stock training at Stanford. She's been publishing important articles
Speaker 1: for a good fifteen years, but has really started to
Speaker 1: generate some incredible excitement in recent years because of a
Speaker 1: few studies that she's done that seemed to provide some
Speaker 1: new insights into how and why M D m A,
Speaker 1: into some extent, psychedelics work the way they do. One
Speaker 1: of them involves octopuses and another is studies done on mice,
Speaker 1: but with important implications for understanding why m D m
Speaker 1: A works the way it does and other psychedelics with
Speaker 1: human beings. So cool, Thanks ever so much for joining
Speaker 1: me on Psychoactive. Thank you very much for having me.
Speaker 1: So let me just start off the first most basic question.
Speaker 1: We now have these studies and by the way'm gonna
Speaker 1: sometimes say M D M A and psychedelics. Sometimes I'll
Speaker 1: say m d M A and other psychedelics, as m
Speaker 1: d M A isn't quite a psychedelic. So if I
Speaker 1: go back and forth, just I hope our listeners will
Speaker 1: give me a little of forgiveness there. But but the
Speaker 1: first questions, we know there's been studies, you know, you
Speaker 1: do studies on animals at the beginning to show the
Speaker 1: safety of a drug, to make sure that M D
Speaker 1: M A or something is not toxic. But just the
Speaker 1: very basic question, if we already have a good sense
Speaker 1: that these drugs are having an impact on humans, say
Speaker 1: in a therapeutic context and therapeutic value, why even bother
Speaker 1: with studies and other animals. Yeah, that's a great question,
Speaker 1: and it's actually something I've debated a little bit with
Speaker 1: people who are very invested in, you know, pursuing the
Speaker 1: clinical trials. They cost a lot more money, So why
Speaker 1: why do we need the mechanism? And the reason is
Speaker 1: is because you know, while many of these drugs have
Speaker 1: been used in traditional healing practices for years and years
Speaker 1: and years centuries, we are using them differently. Necessarily, we're
Speaker 1: using them differently because we are embedding these practices in
Speaker 1: a different culture, and we are trying to treat people
Speaker 1: who are raised in a different culture. And so if
Speaker 1: we're going to try and adapt them for use the
Speaker 1: way that we want to use them, we really need
Speaker 1: to have a strong basis and understanding what they're doing,
Speaker 1: why they're working, so that we can use them appropriately,
Speaker 1: so that we don't inadvertently cause harm when we're trying
Speaker 1: to apply them in new ways, so that we understand
Speaker 1: both the limit patitions, the constraints, and the opportunities that
Speaker 1: work in our context. And I will just back up
Speaker 1: and say one more thing, which is that I think
Speaker 1: that because of the way science gets reported in our
Speaker 1: newspapers and then the lay press, you know, there's this
Speaker 1: impression that we understand a lot of things from doing
Speaker 1: studies in humans exclusively, but almost all of the mechanisms
Speaker 1: that we understand we understand because we've been able to
Speaker 1: do very basic studies in animal models. Right. So, you
Speaker 1: know you mentioned my interest in oxytocin. Almost everything we
Speaker 1: know about oxytocin and its involvement and regulating love, and
Speaker 1: its involvement at regulating neurotransmitters and the connections between neurons
Speaker 1: and how signals get transmitted between those brain cells. All
Speaker 1: of those studies were done in animals, and then we
Speaker 1: extrapolated from those two humans based on similarity. These that
Speaker 1: we know exists between mice and human brains. Oxytocin. That's
Speaker 1: the drug that's kind of known as the love drug
Speaker 1: or the hug drug, the one that gets released when
Speaker 1: the mother nurses her baby or when people make love
Speaker 1: or things like that. That's right, that's right. And the
Speaker 1: other drugs that everybody talks about is serotonin, the neurochemical
Speaker 1: that people have implicated in mood and depression. And that
Speaker 1: all of these drugs like Prozac that are selective serotonin
Speaker 1: reuptake inhibitors or s s r e s. These molecules,
Speaker 1: everything we know about them, we know about them because
Speaker 1: of animal studies that we've been extrapolated to humans. I see.
Speaker 1: So now, when we think about animal studies, typically, you know,
Speaker 1: we think about mice or rats, or maybe you might
Speaker 1: think about things like you know, primates, apes and orangutangs
Speaker 1: or or maybe even dolphins. You know, things that are
Speaker 1: known for high intelligence and are sort of closer to us.
Speaker 1: But you decided to work with octopuses and to administer
Speaker 1: NDMA to octopus is why. Yeah. So basically, I mean,
Speaker 1: I think it's a very strong tradition in science to
Speaker 1: try and understand human emotion and cognition and disease by
Speaker 1: focusing on the closest relative that we can do these
Speaker 1: kinds of experiments in, and then that way we presume
Speaker 1: that we will be able to understand some sort of rules,
Speaker 1: and because they're closely related, it's easier to make that extrapolation.
Speaker 1: But the approach that we decided to take was one
Speaker 1: that had kind of been in the scientific literature for
Speaker 1: a while. It was actually proposed by Jay z Young,
Speaker 1: who's really important physiologist and ethologists in neuroscience and behavioral
Speaker 1: studies of animals, and he said, what you really want
Speaker 1: to do is to go for the animal that is
Speaker 1: evolutionarily most distant from us, so most different, separated by
Speaker 1: as much evolutionary time as you can, who also exhibits
Speaker 1: some of the complex behaviors that we do you and
Speaker 1: that by comparing those maximally different brains to each other,
Speaker 1: then you can sort of overlook or look past all
Speaker 1: the extraneous historical accidents of evolution and figure out the
Speaker 1: rules for how to build complexity and so we decided
Speaker 1: that we wanted to understand how seratonin, this neuro transmitter
Speaker 1: that I mentioned, has been implicated in almost every function
Speaker 1: you can think of, including mood and feeding and temperature regulation,
Speaker 1: and we wanted to know how old is its role
Speaker 1: in regulating social behaviors and can we deduce any of
Speaker 1: those rules by looking at an octopus? And so basically,
Speaker 1: I mean, if I understand it, so, an octopus is
Speaker 1: quite radically different than human beings. They don't have the
Speaker 1: same kind of brain. All the things that the parts
Speaker 1: of the brain are supposedly light up when you do mbma,
Speaker 1: they don't even have that. So the common element is
Speaker 1: that they have these serotonin transporters. Is that the key
Speaker 1: thing that makes it relevant here. Yeah, So that was
Speaker 1: actually the idea we were testing. Their brains don't look
Speaker 1: anything like our brains. Their brains actually look much more
Speaker 1: like a snail's brain because they are mollusks and they
Speaker 1: don't have the same sort of organization of centralizing all
Speaker 1: the brain functions into one but they have a central brain,
Speaker 1: but they also have distributed brains controlling each of their arms.
Speaker 1: And so in the absence of all of the brain
Speaker 1: regions that we think of as being important for social
Speaker 1: behaviors or cognition. That they were able to respond to
Speaker 1: the m d M A in pretty similar ways to
Speaker 1: the ways that mice and rats and humans respond to
Speaker 1: m d M A. In other words, when we measured
Speaker 1: their pro social behavior, their desire to spend time in
Speaker 1: the chamber that had the other octopus in it increased
Speaker 1: after we gave them m d M A. That told
Speaker 1: us that all of the anatomical things that were used
Speaker 1: to attributing the functions of these drugs too really are
Speaker 1: sort of extraneous detail, and that they're accidents of the
Speaker 1: evolutionary history of that animal, and that the thing that
Speaker 1: really matters for encoding this social function of serotonin is
Speaker 1: at the level of molecules and specifically the proteins that
Speaker 1: encode the serotonin transporter which m d M A binds to,
Speaker 1: and that just by having that, it's enough to override
Speaker 1: the normal behavior that we see in octopuses, which is,
Speaker 1: you know, they're not social. In fact, if you put
Speaker 1: two octopuses in it, this species in particular, if you
Speaker 1: put them in a tank together, they will kill each other.
Speaker 1: And so M D M A has this very powerful
Speaker 1: ability to override that and make them desire social interaction
Speaker 1: and spend more time with the other animals. I have
Speaker 1: to tell you what I mean. Until like a couple
Speaker 1: of days ago, when I started prepping for our conversation,
Speaker 1: almost everything I knew about octopus this was from seeing
Speaker 1: that Academy Award winning documentary by the South African fellow
Speaker 1: Craig Foster, My Octopus Teacher, which I loved. It talks
Speaker 1: about the sort of wariness in a social ability of octopus,
Speaker 1: but obviously there's this bonding that goes on there between them.
Speaker 1: Although some people said, maybe we're just anthropomorphizing, you know,
Speaker 1: attributing to the octopus human characteristics and behavior more than
Speaker 1: its appropriate, but it was I don't know. I mean,
Speaker 1: as I'm reading your study, I just kept thinking about that.
Speaker 1: Have you seen that film? I have. I have seen it.
Speaker 1: It was beautifully shot film. But I agree with the
Speaker 1: concern that we're anthropomorphizing. And I'll just put it out
Speaker 1: there that Aristotle actually thought that octopuses were the stupidest animal,
Speaker 1: and that was because back in his time, you know,
Speaker 1: there were abundant in the sea and they were sort
Speaker 1: of easy to catch. Because all you had to do
Speaker 1: is put a rod in front of them, and they would,
Speaker 1: out of this intense sense of curiosity, reach out and
Speaker 1: grab the rod, and then you just pull the rod
Speaker 1: up and the octopus would come with it. So, you know,
Speaker 1: people have been studying octopuses for thousands of years, and
Speaker 1: depending on your perspective, whether you consider them an easy
Speaker 1: to catch food source or whether you are making netslix
Speaker 1: documentary about them, the tendency to anthropomorphized can lead you
Speaker 1: to very different conclusions about what they're capable of. And
Speaker 1: so one thing I would say is that even though
Speaker 1: we characterize them as being a social most of the time,
Speaker 1: in fact, they do suspend that a sociality during brief
Speaker 1: times that are important for their behavior. So the species
Speaker 1: that we were studying in the M. D m A
Speaker 1: paper was octopus by maculoids, or the California two spot octopus,
Speaker 1: and that octopus will suspend this sort of aggressive stance
Speaker 1: that they take to other members of their species when
Speaker 1: they are mating. We know that they must have the
Speaker 1: circuitry for social behavior somewhere in their brains, and that,
Speaker 1: for whatever reason that we haven't really understood, evolutionary selection
Speaker 1: pressures have made it so that it's more beneficial to
Speaker 1: whatever strategy they're using to mostly be a social and
Speaker 1: turn off that sociality except when they're going to be mating. Yeah. Yeah,
Speaker 1: I was reading about octopus before talking with you. I
Speaker 1: mean I saw that not all octopuses are a social
Speaker 1: I think you just pointed out, like there's something called
Speaker 1: a larger Pacific strike octopus, which is a little more social.
Speaker 1: So the element of there being a bit of loaners, right,
Speaker 1: was kind of relevant to the research because you're looking
Speaker 1: at the sociability associated with m d m A. That's right. Well,
Speaker 1: I mean, honestly, we didn't know what was going to happen.
Speaker 1: We started the experiment thinking, you know, maybe what's going
Speaker 1: to happen is is that sarahtonin is old or the
Speaker 1: transmitter and the transporter is there. But when we give
Speaker 1: the m d M A, it's just going to induce
Speaker 1: sort of a hyperactive behavior or something similar to what
Speaker 1: emphetamines might do to the brain of a mammal. Because
Speaker 1: it's in the amphetamine class and saratonin, we didn't know
Speaker 1: if this pro social function was as old as some
Speaker 1: of its other functions, and we didn't know if it
Speaker 1: could bind to it, if it was going to also
Speaker 1: bind to other transporters and do other things. So we
Speaker 1: wanted to start with this social because that was the
Speaker 1: question that we were interested in, but also octopuses because
Speaker 1: they're so a social When we just did the baseline
Speaker 1: measurements of how much time they spend in the social
Speaker 1: chamber versus the chamber that had a little toy object
Speaker 1: in it, they spent almost all of their time in
Speaker 1: the toy object chamber, which was maximally distant from the
Speaker 1: other octopus. And so that made a really nice baseline measurement.
Speaker 1: And so when we gave them m D M A
Speaker 1: and the behavior shifted hundred and eighty degrees and now
Speaker 1: they spent most of their time in the social chamber.
Speaker 1: We didn't need very many animals to be able to
Speaker 1: statistically draw the conclusion that, you know, the M D
Speaker 1: M A had this effect on changing their social behavior.
Speaker 1: So cool. When it comes to administering in the email
Speaker 1: of the drugs to the mice or other animal, how
Speaker 1: do you do it is an injection or another means?
Speaker 1: And how do you figure out the right dosing levels
Speaker 1: and what's comparable too levels and humans. Yeah, So with
Speaker 1: the mices sort of straightforward. We just give them an
Speaker 1: injection what we call an I P injection interpretornal injection,
Speaker 1: and we're just injecting it directly into their abdomen. And
Speaker 1: because most of these psychedelics are very leoad brain barrier permeable,
Speaker 1: it gets into the brain. And we test the doses
Speaker 1: to make sure that we start with the human dose
Speaker 1: and adjust it for weight, and we just kind of
Speaker 1: tietrate until we see the effect, and remarkably, the effects
Speaker 1: seem to be pretty close. The dose that we would
Speaker 1: use in a human is usually within ten times of
Speaker 1: what we see in a mouse, tentimes more ten times
Speaker 1: less or the same, and so that was reassuring. That
Speaker 1: can change because mouth metabolism is very fast, so we
Speaker 1: have to be careful about that, so we want to
Speaker 1: test it every time. The trickier one was definitely the
Speaker 1: octo us because we didn't know how to deliver it.
Speaker 1: The octopus is a secreature and so the way that
Speaker 1: it receives drugs normally, the equivalent would be if we
Speaker 1: put it in the water is on their gills and
Speaker 1: it's sort of washing over their gills and getting into
Speaker 1: the blood directly from the gills, and so putting m
Speaker 1: d M A and the water might be something like
Speaker 1: figuring out a way of making aerosolized m d M
Speaker 1: A and putting somebody in a hot box with aerosolized
Speaker 1: m d M A for thirty minutes. So we really
Speaker 1: weren't sure, but we decided to go ahead and try
Speaker 1: it anyway. And this is true with all experiments that
Speaker 1: we do an octopus, we never want to just assume
Speaker 1: that it's the same because their physiology is so different.
Speaker 1: They don't have a liver. They have something between a
Speaker 1: liver and a pancreas. Those cells have some of the
Speaker 1: features of both. It's not clear that they have a
Speaker 1: blood brain barrier. They don't even metabolize oxygen in the
Speaker 1: same way that we do. So we had to test
Speaker 1: it and we just titrated. We start high and then
Speaker 1: work our way backwards until we got to the right dose.
Speaker 1: Uh huh, Yeah, so cool. When you're testing animals given psychedelics,
Speaker 1: is it getting the permission from the university or from
Speaker 1: the funding agencies is any different than giving animals other
Speaker 1: types of drugs. Yeah, we have to go through all
Speaker 1: of the regulatory requirements for being approved for giving Schedule
Speaker 1: one medicines, and so that's a regulatory process that we
Speaker 1: have to do, but both the federal and the state
Speaker 1: level took us about a year to get all of
Speaker 1: those licenses approved. And then once we get the licenses,
Speaker 1: then we have to go back to our Animal Care
Speaker 1: and Use Committee and work with them back and forth
Speaker 1: to make sure that we have done all the appropriate
Speaker 1: safeguarding measurements and that we're really making sure that we
Speaker 1: are doing these experiments in the safest and least stressful
Speaker 1: way for the animals. The octopus is sort of a
Speaker 1: unique situation because currently in the United States, octopuses are
Speaker 1: have the same regulatory requirements as all other invertebrates, so
Speaker 1: flies and worms and cockroaches and all the invertebrates, right,
Speaker 1: but we are sensitive to the fact that octopus is
Speaker 1: their behavioral repertoire is much more complex, and we certainly
Speaker 1: don't agree with Aristotle that they're the dumbest animals. So
Speaker 1: we have taken care to apply all the same standards
Speaker 1: that we use for mouth studies for the octopus to
Speaker 1: make sure that we're treating them in a way that
Speaker 1: respects their intelligence and their ability to feel pain and
Speaker 1: take care of them. We'll be talking more after we
Speaker 1: hear this add You know, the thing I was wondering
Speaker 1: in reading about your study was that I thought back
Speaker 1: to the famous rat park studies that Bruce Alexander did
Speaker 1: with I think it was mice and cocaine. This is
Speaker 1: back in the seventies, I think, and this is the
Speaker 1: famous experiment where, you know, everybody knows the basic studies
Speaker 1: of you put mice or monkeys in a cage and
Speaker 1: you make available to them cocaine or a kind of
Speaker 1: saline solution, alternative placebo thing. Many of them will just
Speaker 1: keep injecting or consuming the cocaine until they die. But
Speaker 1: what Bruce Alexander showed was that when you did the
Speaker 1: same experiment with animals that were in a kind of
Speaker 1: wildlike environment, in fact, they either had no interest in
Speaker 1: the cocaine, or if they did show any interest, they
Speaker 1: used it in a sort of moderation. It didn't fundamentally
Speaker 1: affect their lives. And it was all about the importance
Speaker 1: of setting, especially in terms of determining how people consume drugs,
Speaker 1: why they get into problematic relationships, all this sort of
Speaker 1: thing I wondered, if you've been doing this study and
Speaker 1: somehow been able to do it with octopus who were
Speaker 1: in the wild where they have to have a greater fear,
Speaker 1: presumably about predators, do you think you would have had
Speaker 1: a different Well, it's a good question, and it's definitely
Speaker 1: something that we have thought a lot about. I mean,
Speaker 1: the rat part experiment. When I first started my lab
Speaker 1: back in two thousand fourteen, that study had a big
Speaker 1: effect on me because what it really made me realize
Speaker 1: is that when we started doing a lot of studies
Speaker 1: in rats, especially, but mice also, for a number of
Speaker 1: practical technical reasons, it was easier to keep isolation housing them.
Speaker 1: But rats and mice are both social animals, and so
Speaker 1: a lot of the conclusions we drew from some of
Speaker 1: those early drug addiction studies were probably wrong because we
Speaker 1: were essentially studying animals who were enduring sort of social isolation, stress,
Speaker 1: and maybe more depressed, maybe more vulnerable to their drug
Speaker 1: environment because they weren't getting all of the social support
Speaker 1: that would be normal for their environment. Octopuses are sort
Speaker 1: of different than that. So octopus is in the wild
Speaker 1: or a social they prefer not to be living with
Speaker 1: other animals, except for as you mentioned, the larger Pacific
Speaker 1: striped octopus or LPSO, seems to be the only decidedly
Speaker 1: social octopus. But for the most part, octopuses prefer to
Speaker 1: live a socially. We had to design the experiment taking
Speaker 1: that into consideration because we certainly didn't want to put
Speaker 1: them into a stressful situation by essentially allowing them to
Speaker 1: attack each other, which is why we kept the other
Speaker 1: octopus underneath the flower pots, so that maybe they showed
Speaker 1: aggressive postures but couldn't actually hurt each other, and taking
Speaker 1: that into consideration, also didn't use a different essay that
Speaker 1: we use in mice that requires them to live together overnight,
Speaker 1: because we knew that they were a social So we
Speaker 1: always have to take those kinds of how do they
Speaker 1: live in the wild into consideration when we're trying to
Speaker 1: design experiments and not accidentally retesting the stress effects of
Speaker 1: living in a way that they are not ethologically suited
Speaker 1: to live when we do the experiment right, because presumably
Speaker 1: though a sociability was an evolutionary thing that developed, right
Speaker 1: in terms of their survival, the ones that survive are
Speaker 1: the ones that are smarter, and maybe the ones that
Speaker 1: are more a social I mean, you know, one thing
Speaker 1: that I find to be fascinating and kind of what
Speaker 1: keeps drawing me back to wanting to do more studies
Speaker 1: than octopus is that all of the other cephalopods are social. Right,
Speaker 1: So nautilus has a shell, that's true, But squid and
Speaker 1: cuttlefish don't have an external shell either, and yet they
Speaker 1: are very social. And so there's something separate about octopus.
Speaker 1: Is maybe that because they're hunting for fish and they've
Speaker 1: taken on predatory behaviors that are similar to other top predators,
Speaker 1: and that they for some reason it's not advantageous to
Speaker 1: do pack hunting. We don't really know. And so this
Speaker 1: is why I'm so fascinated by the larger Pacific striped octopus,
Speaker 1: because somehow something is different, and that species of the
Speaker 1: three d or so known species of octopus is the
Speaker 1: one that has evolved the social pattern of living. And
Speaker 1: it would be I think fascinating to know what was
Speaker 1: the selection pressure that pushed them to that type of
Speaker 1: living that's so different from all the rest. But presumably
Speaker 1: be harder to discern the impact of M D M
Speaker 1: A among creatures that have a higher level of sociability. Well, so,
Speaker 1: I mean that's actually a pretty good segue to talk
Speaker 1: about what m d m A does in mice right there.
Speaker 1: So basically we knew that m d m A already
Speaker 1: had acute pro social effects in mice and in humans,
Speaker 1: and some of the work that supported that actually was
Speaker 1: from behavioral tests that are very similar to the one
Speaker 1: that we did in octopuses. So I'm just putting the
Speaker 1: animals in a large arena that's divided into three rooms
Speaker 1: and just measuring how much time they spend in each
Speaker 1: of the three rooms, one of which has an other
Speaker 1: social animal and one of them that doesn't. And that
Speaker 1: was sort of looking at what happens when you're given
Speaker 1: the drug and the animal is experiencing the acute effects
Speaker 1: of the drugs. So the altered state of consciousness plus
Speaker 1: this Recreational users of m d m A are known for,
Speaker 1: you know, cuddle puddles and lots of pro social hugging
Speaker 1: and wanting to be close to other people, right, and
Speaker 1: we see that same behavior in mice and in octopuses.
Speaker 1: But we were in my lab already studying another phenomenon.
Speaker 1: We were interested in the developmental regulation of social behaviors,
Speaker 1: because we know that a person's way of being social
Speaker 1: changes over their lifetime. Right, So, teenagers are famously they
Speaker 1: love to hang out with each other, they have, you know,
Speaker 1: three hundred friends. They're always on the phone. They just
Speaker 1: can't get enough of social interaction. But as you get older,
Speaker 1: you kind of you like to be social, but jeez,
Speaker 1: you know, sometimes you need some quality alone time to
Speaker 1: gather your thoughts and replenish your social resources, if you will.
Speaker 1: And so that change across development suggested to us that
Speaker 1: there must be something like a critical period for social behaviors,
Speaker 1: and we thought it was important to try and understand
Speaker 1: the neural mechanisms of that, because those changes in the
Speaker 1: way that we learn from our social environment probably have
Speaker 1: a big impact on things like peer pressure and also
Speaker 1: probably impact Why it is that when you have a
Speaker 1: social injury when you're very young, it has a much
Speaker 1: more devastating long term consequence than if you have a
Speaker 1: social injury when you're old. Why we do things like
Speaker 1: we safeguard children, why we make sure that they're not
Speaker 1: exposed to violent television content, and why we sort of
Speaker 1: monitor to make sure that they are not receiving damaging
Speaker 1: information when social information when they're young. And so what
Speaker 1: my live set out to do is to use a
Speaker 1: different essay. So now we're not just measuring acute effects
Speaker 1: of social interactions. We're using an assay called social conditioned
Speaker 1: place preference, which is just animals being put in a
Speaker 1: chamber and we just have two types of betting on
Speaker 1: the floor, and we just take a baseline measurement just
Speaker 1: to make sure that they don't have some pre existing
Speaker 1: bias for one of the two types of betting. We
Speaker 1: just let them run around for thirty minutes on the
Speaker 1: two types of betting, measure how much time they spend
Speaker 1: on each, and then we put them in a new
Speaker 1: chamber with one of the two types of betting, and
Speaker 1: this time they're paying for twenty four hours with their
Speaker 1: social group members. And then we put them for twenty
Speaker 1: four hours on the other type of betting, this time
Speaker 1: by themselves. And then we take another measurement, asking how
Speaker 1: much time do they now after they formed this association
Speaker 1: between the betting and the social environment, how much time
Speaker 1: do they spend in each of those two types of bettings.
Speaker 1: And by doing that, what we've discovered and other people
Speaker 1: have shown as well, is that mice, especially juvenile mice,
Speaker 1: will form a long lasting wrong positive association between the
Speaker 1: betting and a social environment, and a negative association to
Speaker 1: the betting associated with being by themselves and that ability
Speaker 1: to learn from their social environment or the rewarding nature
Speaker 1: of that social environment. What we discovered is is that
Speaker 1: as the animals get older, that goes away, and that
Speaker 1: attenuation or that diminishment of the ability to learn from
Speaker 1: the social environment we describe as a critical period for
Speaker 1: social reward learning and critical period. I mean, when I've
Speaker 1: heard you talk about this, it is connected to sort
Speaker 1: of that notion of imprinting when certain types of birds,
Speaker 1: maybe migratory birds or birds that leave the mother very
Speaker 1: early hatch, that they attached to the first thing that
Speaker 1: they encounter, whether it could be a human being, it
Speaker 1: could be another animal, it could even be another inanimate object.
Speaker 1: Is that the kind of sort of simplistic notion of
Speaker 1: the critical period that's relevant here? Absolutely? In fact, that
Speaker 1: imprinting behavior and snow geese was the first behavior that
Speaker 1: Conrad Lorenz back in nineteen thirty five described and coined
Speaker 1: the phrase critical period to describe, and what he was
Speaker 1: referring to is that long lasting attachment that you're describing
Speaker 1: that happens, but only within the first forty eight hours
Speaker 1: after hatching. After that, they don't form that long lasting attachment.
Speaker 1: That whatever's in their environment that they've attached to ceases
Speaker 1: to be relevant in the same way and ceases to
Speaker 1: be a salient signal that allows them to form a
Speaker 1: long lasting attachment. And so that window of time where
Speaker 1: the animal is much more sensitive to their environment and
Speaker 1: able to form these long lasting memories. Conrad Lorenz called
Speaker 1: a critical period, and he did that in nineteen thirty five,
Speaker 1: but since then there have been lots and lots of
Speaker 1: critical periods that have been described. I think most people
Speaker 1: are familiar in their own lives with the critical period
Speaker 1: for language learning. So if you've ever tried to learn
Speaker 1: a language later on in life, it's much harder to learn.
Speaker 1: You have to practice, you have to study. You will
Speaker 1: always have an accent when you speak it. You won't
Speaker 1: speak it with the same sort of fluidity and ease
Speaker 1: as you did your native language. My sister seems to
Speaker 1: be the exception to this rule because she doesn't seem
Speaker 1: to have a critical period for languages. She speaks like
Speaker 1: five or six fluently in a couple more just as
Speaker 1: needed basis. But for most people, you know, the language
Speaker 1: that you learned as a child is the one that
Speaker 1: you know and the one that you speak fluidly without
Speaker 1: an accent, and anything else later on is much harder
Speaker 1: and not as fluid, And so that is reflecting the
Speaker 1: fact that there's a critical period for language learning. But
Speaker 1: there are other critical periods as well. So there are
Speaker 1: critical periods for organizing the visual system, for organizing the
Speaker 1: touch system, and probably clinically, the one that we are
Speaker 1: sort of most fascinated by and will follow up with
Speaker 1: is that there's a critical period for recovering motor function
Speaker 1: after you have a stroke. So right after you have
Speaker 1: a stroke, you have this short window of time six
Speaker 1: weeks seems to be this sort of sweet spot where
Speaker 1: if you do intensive physical therapy, that's where you're going
Speaker 1: to get the most recovery. But after that window is closed,
Speaker 1: you know you're not going to get much more motor
Speaker 1: recovery after that window is closed. So now your focus
Speaker 1: was on social reward learning aspects of critical period. So
Speaker 1: is that a relatively newer concept or also one that
Speaker 1: goes back a while. No, So we discovered the social
Speaker 1: reward learning critical period. And we were able to discover
Speaker 1: it because we were able to do this in animal studies,
Speaker 1: so we were able to look at fifteen different ages,
Speaker 1: we were able to look at both sexes. It was
Speaker 1: hundreds and hundreds of mice and really characterized the developmental timeline.
Speaker 1: But that being said, you know, people who do human
Speaker 1: cognition studies and child development studies had already sort of
Speaker 1: had an inkling that something like this must have exists
Speaker 1: just by doing comparisons between two different ages and the
Speaker 1: ways that children process social information. There was an idea
Speaker 1: out there that it might exist, but it wasn't formally
Speaker 1: demonstrated until we we showed it in mice. I see,
Speaker 1: and when you're administering the n D m A to
Speaker 1: the mice, does it make a difference whether these mice
Speaker 1: are the equivalent of juveniles or adolescents or adults. Yeah,
Speaker 1: So when we were trying to characterize the behavioral critical period,
Speaker 1: we also did some studies to try and understand what
Speaker 1: are the cellular and synaptic mechanisms underlying that establishment and
Speaker 1: constraining of that learning and memory to this window. And
Speaker 1: we had implicated oxytocin that we talked about before in
Speaker 1: that process, and we thought, well, we want to be
Speaker 1: able to reopen this critical period because neuroscientists, pretty much
Speaker 1: since we first knew about critical periods, had had the
Speaker 1: intuition that the ability to reopen critical periods is going
Speaker 1: to be immensely powerful as a therapeutic. But oxytocin doesn't
Speaker 1: cross the blood brain barriers. So you might have heard
Speaker 1: in the lay press people talking about intronasal oxytocin, but honestly,
Speaker 1: that just doesn't really worked out. Well, it doesn't get
Speaker 1: into the brain. Whatever affects people are reporting of intronasal
Speaker 1: oxytocin are probably indirect effects on the brain and affects
Speaker 1: that that oxytocin is having in the body, not in
Speaker 1: the brain. And so we thought, well, gosh, you know,
Speaker 1: is there some other way that we might be able
Speaker 1: to trigger this reopening of the critical period. And we
Speaker 1: knew that m d M A had these pro social
Speaker 1: effects and m d M A there was some anecdotal
Speaker 1: evidence that it might also be triggering oxytocin release in
Speaker 1: the central nervous system. And so what we did is
Speaker 1: unlike the octopus experiments and other experiments that had been
Speaker 1: done before we gave the m d M A in
Speaker 1: adult animals. So remember, at the adult age, the critical
Speaker 1: period is closed. So we gave the m d M
Speaker 1: A and then we just way did for forty eight
Speaker 1: hours for all of the acute m d M A
Speaker 1: to wash out of the system, and then we measured
Speaker 1: social reward learning again in the adult animals. And what
Speaker 1: we found is is that forty eight hours after we
Speaker 1: gave the m d m A, that juvenile ability, that
Speaker 1: ability to learn from the social environment, came back in
Speaker 1: the adults. And that restoration of the juvenile behavior in adulthood,
Speaker 1: we thought was very strong evidence that what we've done
Speaker 1: is reopened this critical period. And then at the same time,
Speaker 1: if we gave m d m A to the juvenile animals,
Speaker 1: we had no impact on the magnitude of social reward learning.
Speaker 1: So it wasn't just that the adult animals are sort
Speaker 1: of satiated and that we just drained the emotional bucket
Speaker 1: and made them thirsty for social again, because if that
Speaker 1: was the case, then we would have expected that depriving
Speaker 1: the animals and juveniles would also restore an increased level
Speaker 1: of social reward learning and it didn't. And so taken together,
Speaker 1: those two things really convinced us that what we're looking
Speaker 1: at is a reopening of a critical period, not some
Speaker 1: sort of satiation with sociality. Right. And you saw this
Speaker 1: reopening though in the adult mice that were in social situations,
Speaker 1: but not the ones that had been isolated, right. So
Speaker 1: that is a really interesting component of this study which
Speaker 1: I think lends further support to the idea that critical
Speaker 1: period reopening is what really accounts for the incredible therapeutic
Speaker 1: effects that we're seeing with these drugs. So one of
Speaker 1: the things that I think probably your audience will be
Speaker 1: familiar with is that psychedelics in particular have this feature
Speaker 1: of being set and setting dependent. Right, So if you're
Speaker 1: around people that you feel comfortable with or giving off
Speaker 1: good vibes, if you will, then the M d m
Speaker 1: A experience can be very different than if you're feeling
Speaker 1: threatened or anxious or not safe. And that phenomenology of
Speaker 1: the set and setting dependence of psychedelic drugs also translates
Speaker 1: to the therapeutic effects, right. So you can't just take
Speaker 1: M d M A and go to a rave and
Speaker 1: expect that your PTSD is going to be cured, you
Speaker 1: really want to pair the m d M A with
Speaker 1: the context of psychoanalysis to look at the trauma that
Speaker 1: you're trying to deal with, and then rewriting those memories
Speaker 1: around the trauma during the trip. And we think actually
Speaker 1: afterwards as well, and this context dependence or you know,
Speaker 1: the set and setting, but we call it context dependence
Speaker 1: of psychedelics effects we think are different than for example,
Speaker 1: m d M A has like a mild social anxiolytic property.
Speaker 1: Psilocybin and LSD and ketamine have anti depressive properties, but
Speaker 1: those antidepressive and anxiolytic properties of the drugs don't seem
Speaker 1: to be context dependent, right, And so these drugs do
Speaker 1: a lot of different things in the brain. Some of
Speaker 1: the properties are context dependent and some of them are
Speaker 1: in not. And we think that the exciting possibility is
Speaker 1: that the remarkable sort of this is going to be
Speaker 1: a cure for neuro psychiatric disease. Part of these drugs
Speaker 1: comes from that context dependence, and so we were really
Speaker 1: excited that unlike other studies which had looked at the
Speaker 1: antidepressive properties of the anxiolytic properties and shown that these
Speaker 1: were not context dependent. Critical period reopening is context dependent.
Speaker 1: So you can only reopen the social critical period if
Speaker 1: you give M d M A in the social context.
Speaker 1: And we think that the social part of that is
Speaker 1: a little bit of a We have more evidence now
Speaker 1: suggesting that that's a little bit of a red herring,
Speaker 1: because we are excited about the possibility that psychedelics are
Speaker 1: the master key for unlocking critical periods across the brain,
Speaker 1: sort of writ large and if that's true, then we
Speaker 1: would expect that the dependence on the social context is
Speaker 1: true because we're trying to open a social critical period.
Speaker 1: But if we were trying to open a visual critical
Speaker 1: period or a motor learning critical period, then visual experience
Speaker 1: or motor experience during the acute phase of the psychedelic
Speaker 1: would be the important context, not social. And now, when
Speaker 1: you found that what you were finding with M d
Speaker 1: M A was also true with the variety of psychedelics,
Speaker 1: was that surprising to you. Yeah, So that work isn't
Speaker 1: published yet, but I'm happy to briefly mention it. We
Speaker 1: basically did those experiments as a control. I was fairly
Speaker 1: certain that the reason that M D M A was
Speaker 1: having this remarkable ability to reopen the critical period was
Speaker 1: because but so pro social in quality, right, It's acute
Speaker 1: subjective effects are really pro social. But you know, nobody's
Speaker 1: taking LSD and doing a cuddle puddle. In fact, most
Speaker 1: people need to kind of especially if they're having an
Speaker 1: inner directed trip. You know, they need quiet and maybe
Speaker 1: one or two other people, but they're not cuddling the
Speaker 1: way they are with M D M A. And so
Speaker 1: we were really surprised when LSD and psilocybin and ketamine
Speaker 1: and I began all also reopened this critical period. And
Speaker 1: what that suggested immediately to us, and this is what
Speaker 1: we're following up in the subsequent studies, is that the
Speaker 1: acute subjective character of psychedelics really isn't the thing. So
Speaker 1: the thing that makes them all similar is their ability
Speaker 1: to open the critical period. And in fact that the
Speaker 1: thing that they share in common, and which is why
Speaker 1: I call all of them psychedelics, is that they all
Speaker 1: induce an altered state of consciousness. Right, And it's hard
Speaker 1: to define exactly what that means that altered state of consciousness,
Speaker 1: but all of the psychedelics, whether they're dissociative, hallucinogetic, and
Speaker 1: pathogenic or own irogenic. They all have that property of
Speaker 1: inducing that altered state of consciousness, and so our recent
Speaker 1: studies really suggest that maybe what it feels like to
Speaker 1: be in an altered state of consciousness is just what
Speaker 1: it feels like to open critical period. But now you're
Speaker 1: probably using that phrase altered state of consciousness in an
Speaker 1: hour sense because given the name of this podcast, right, psychoactive,
Speaker 1: which essentially implies altered state of consciousness, And we think
Speaker 1: about that applying really to almost all psychoactive substances, So
Speaker 1: not just the psychedelics, but cocaine or opioids, or for
Speaker 1: that matter, it could be caffeine or nicotine or you know,
Speaker 1: any range of others insufficient doses. So what about those
Speaker 1: other substances, I mean, they are altering consciousness, Is it
Speaker 1: just that they're altering it in a different way or
Speaker 1: different degree. Yeah, So I guess I would quibble with
Speaker 1: the idea that they're all altering consciousness. They're all altering
Speaker 1: brain function, I guess. And so I guess it sort
Speaker 1: of depends on how broadly you want to define consciousness.
Speaker 1: If you want to define it really broadly and you
Speaker 1: want to say consciousness is just in the sense of
Speaker 1: conscious versus unconscious. Then every anesthetic is also a psycho
Speaker 1: well psychoactive. But when people say the altered state of
Speaker 1: consciousness induced by psychedelics, I think they're referring to a
Speaker 1: very narrow sense of what it means to be conscious. Again,
Speaker 1: it's a little bit hard to define. I mean, I
Speaker 1: feel like philosophers have written whole books about what is
Speaker 1: the interesting sense of the word consciousness, and so I
Speaker 1: don't really want to spend too much time on that.
Speaker 1: But what I will say is is that the shared
Speaker 1: ability of psychedelics to alter the sense of consciousness that's
Speaker 1: different from other psychoactive drugs like cocaine and nicotine and
Speaker 1: alcohol and even marijuana, seems to be related to their
Speaker 1: therapeutic effects, right, Because it's not like people are curing
Speaker 1: drug addiction with cocaine. It's not like people are curing
Speaker 1: PTSD with cocaine, right. In fact, cocaine's psychotropic or psychoactive
Speaker 1: effects are more likely to leave do abuse and addiction
Speaker 1: like behaviors. They incidentally take a reward and make it
Speaker 1: context independent, and they're really what I would call drugs
Speaker 1: that induce Cocaine in particular, induce hyper plasticity, And so
Speaker 1: by plastic see, what I mean is is that synapses
Speaker 1: in the brain, which are the connections between neurons and
Speaker 1: how they communicate with each other, the weights that are
Speaker 1: assigned to each of those synapses change as you encode memories.
Speaker 1: And we think that that plasticity of the synaptic weights
Speaker 1: is what's responsible for encoding memories. And what cocaine seems
Speaker 1: to do is massively increase the number of synapses and
Speaker 1: dendritic sprouting and create a whole bunch of extra memories
Speaker 1: that are around using cocaine, enjoying cocaine, associating every positive
Speaker 1: feeling you've ever had with cocaine, and that sort of
Speaker 1: hyperplastic response is very different from what we see with psychedelics. Well,
Speaker 1: let me ask you this school, I mean, because let
Speaker 1: me just throw in two other drugs here that kind
Speaker 1: of fall in between. I mean, obviously m D M
Speaker 1: A is amphetamine based, and so one question is what
Speaker 1: about other types of amphetamine. They share some things in
Speaker 1: common with cocaine, some things in common with M D
Speaker 1: M A. Of the other one is what about th HC,
Speaker 1: which kind of falls in between the kind of altered.
Speaker 1: In fact, many people say it does create altered state
Speaker 1: of consciousness in ways that sometimes can resemble the psychedelics.
Speaker 1: So what about those two Amphetamine and t HC. Yeah,
Speaker 1: so we haven't actually tested either one directly, but I
Speaker 1: suspect that emphetamine is going to look very much like cocaine,
Speaker 1: which you know, cocaine does not reopen the critical period,
Speaker 1: but it does induce these addiction like behaviors and addiction
Speaker 1: like changes in synapsis. Th HC is definitely a strange one,
Speaker 1: and it's an in between case, and we really don't know.
Speaker 1: And one of the things about TAHC that I've always
Speaker 1: been sort of fascinated about is that it seems to
Speaker 1: be a great imitator. So if you've, you know, mostly
Speaker 1: been intoxicated with alcohol and then you start doing th HC,
Speaker 1: you know you're high, your teach the highest sort of mellow.
Speaker 1: But after you do t HC, after you've tried any
Speaker 1: of the psychedelics, then suddenly it can take on a
Speaker 1: sort of psychedelic character. And I don't have any clue
Speaker 1: about what that's about. The reason that we sort of
Speaker 1: didn't focus on THHC in our experiments is that t HC,
Speaker 1: especially at very high doses seems to induce a certain
Speaker 1: amount of paranoia in people, and we actually think we
Speaker 1: have a hypothesis about why that is. But you'll have
Speaker 1: to invite me again for a different podcast to talk
Speaker 1: about that one. Okay, well, so let's just talk about
Speaker 1: some of the other implications of the study. So you
Speaker 1: find that you know it's working, and obviously you know
Speaker 1: m d m A, you know, and is sort of
Speaker 1: a pathogen heartwarming, cuddly whereas we think about the psychedelics,
Speaker 1: and sometimes I guess one of the theories is that
Speaker 1: the intensity of the sort of spiritual or mystical experience
Speaker 1: is part of what is associated with their efficacy. But
Speaker 1: one of the other things that I saw you pointing
Speaker 1: out is that, you know, we've typically at least I've
Speaker 1: typically thought about you do m d m A just
Speaker 1: psycholics and you have a psychotherapeutic you work with the
Speaker 1: therapist immediately thereafter. But you're pointing out that this critical
Speaker 1: period that gets opened, it's not just for a few
Speaker 1: hours or something. It can be quite a bit longer,
Speaker 1: and that the longer the drug experience last, maybe the
Speaker 1: longer the critical period last. And so just talk about
Speaker 1: that and the implications of that. Yeah, So I mean
Speaker 1: I mentioned that we were beginning to have some evidence
Speaker 1: that what it feels like to be in this psychedelic
Speaker 1: altered state of consciousness is just what it feels like
Speaker 1: to reopen critical periods. And part of the evidence we
Speaker 1: have for that is this proportionality between how long the
Speaker 1: acute subjective effects of psychedelics last and how long the
Speaker 1: critical period stays open after the psychedelic acute effects have
Speaker 1: worn off. And so just to compare the different drugs,
Speaker 1: so ketamine, you know, most people's acute effects of ketamine
Speaker 1: lass anywhere from thirty minutes to maximum sort of two hours,
Speaker 1: whereas people who take LSD, you know, it's eight to
Speaker 1: ten hours is the typical acute subjective effects last, Whereas
Speaker 1: I began lasts for a really long time. So between
Speaker 1: thirty six and seventy two hour long acute subjective effects
Speaker 1: of I be game. And just like that, what we
Speaker 1: see is that ted amine keeps the critical period open
Speaker 1: for forty eight hours. Psilocybin and m D m A
Speaker 1: seem to keep it open for about two weeks after
Speaker 1: we give the drug LSD for three weeks, and I began,
Speaker 1: you know, we haven't found the outer limit of it,
Speaker 1: but at least a month after we give I BEGANN
Speaker 1: the critical period stays open. And so that has I
Speaker 1: think three really important implications. One is that, as I said,
Speaker 1: it sort of lends further support to the idea that
Speaker 1: critical period reopening is the thing that makes this class
Speaker 1: of drugs a single drug class, the shared property across
Speaker 1: the drugs. The second one is that I think when
Speaker 1: we're designing clinical trials for using these drugs to cure PTSD,
Speaker 1: we're gonna band to be really really careful about out
Speaker 1: making sure that we offer enough support to people after
Speaker 1: the acute subjective effects have worn off, because what's two
Speaker 1: weeks in a mouth could be two months in a
Speaker 1: human right, And what we think this is analogous to
Speaker 1: is putting a person back into this sort of vulnerable
Speaker 1: and sensitive state, just like a child. And so we
Speaker 1: want to offer support to those people. And you know,
Speaker 1: I would very much like to get funding to run
Speaker 1: a clinical trial that looks at the difference between people
Speaker 1: who were given sort of standard of care the way
Speaker 1: the FDA wanted the trials to be designed, and another
Speaker 1: group where instead of just going home and writing in
Speaker 1: your journal and calling into the therapist for the weeks
Speaker 1: after you get to go to something like a retreat
Speaker 1: and you are given the sort of space and support
Speaker 1: and therapy that you need to continue to integrate those
Speaker 1: memories and those traumatic habits that you've developed from your
Speaker 1: being traumatized, that you reintegrate them in to your new
Speaker 1: personality habits and traits and your new world in that
Speaker 1: sort of safe space. So that's the second implication, and
Speaker 1: then the third implication, and this sort of touches on
Speaker 1: what you mentioned about Roland Griffith's studies about the depth
Speaker 1: of the mexical experience. I think that what this is
Speaker 1: telling us is that there are a lot of enthusiasm
Speaker 1: right now, especially from the business world, to rush to
Speaker 1: develop psychedelics that don't have any kind of psychedelic side
Speaker 1: effects if you will so engineer out the mystical experience
Speaker 1: the big trip right and I suspect that those efforts
Speaker 1: will all take miracle drugs like LSD and psilocybin and
Speaker 1: I beginning, which have these very profound ability to change
Speaker 1: memories and potentially cure things like heroin addiction and essentially
Speaker 1: engineer them back down to being something like an S
Speaker 1: s R I, because I think if you get rid
Speaker 1: of that long experience, you're going to interfere with the
Speaker 1: mechanism that is reopening critical periods. So when you're talking
Speaker 1: about this extended length of the critical period, it's not
Speaker 1: just about being cautious about how therapists deal with that period,
Speaker 1: being aware that it's not just about the hours and
Speaker 1: days afterwards, but you're also talking that there's actually this
Speaker 1: bonus that maybe people didn't realize, that there's this extended
Speaker 1: period of time in which the insights can be almost
Speaker 1: harvested and developed even more more thoroughly, more deeply, absolutely, absolutely,
Speaker 1: and in fact I think that this is why for
Speaker 1: really really entrenched memories and really hardcore addictions like heroin addiction,
Speaker 1: the big sort of anecdotal stories that we hear about
Speaker 1: recovery from heroin addiction are all coming from iby game, right,
Speaker 1: not from ketamine or psilocybin, right, Because those memories are
Speaker 1: really entrenched into the fabric or the whole sort of
Speaker 1: network of memories and habits and patterns and personality traits
Speaker 1: that a humans developed over their lifetime, and to undo
Speaker 1: them you probably need to have the critical periods stay
Speaker 1: open for a long time so that you can say, Okay, oh,
Speaker 1: I'm going to the park, and normally I would have
Speaker 1: a heroin craving here, but you know what, I don't
Speaker 1: need that anymore, you know, rewriting those memories around the
Speaker 1: whole whole circuit of memories that surround that very entrenched addiction. Now,
Speaker 1: are there implications on me, for example, about say, multi dosing,
Speaker 1: like giving ketamine five or six days in a row,
Speaker 1: or administering multiple doses of d M A or psilocybi
Speaker 1: els D over a period of days or weeks. Anything
Speaker 1: you can say about that stuff, we see added benefits,
Speaker 1: reduced benefits. Yeah. So, honestly, when we first started these experiments,
Speaker 1: I basically have the intuition that, you know, the longer
Speaker 1: you can keep it open, the better, and that that
Speaker 1: would help you to have the most access to those
Speaker 1: sort of calcified memories, if you will. But I'm beginning
Speaker 1: to think that actually there probably is an opportunity to
Speaker 1: stabber them, especially because you sort of hinted at this
Speaker 1: and the question. Especially the serotonin psychedelics seem to have
Speaker 1: this property of causing desensitization or tolerance very quickly. So
Speaker 1: people who do micro dosing of psilocybin, you know, not
Speaker 1: everybody has the same experience, but a lot of people
Speaker 1: will report that very quickly the effects of the drug
Speaker 1: seems to attenuate, right. And so what we have also
Speaker 1: discovered is that we've kind of a little bit taken
Speaker 1: down the primacy of the serotonin to a receptor, because
Speaker 1: while psilocybin and LSD obviously really you know, we have
Speaker 1: to activate the serotonin too a receptor in order to
Speaker 1: get these critical period reopening, ketamine m D M A
Speaker 1: and I began don't care about the serotonin receptor. In fact,
Speaker 1: there's evidence that ketamine is working through a different receptor
Speaker 1: called an m D A. I began is probably working
Speaker 1: through the cappa opioid receptor m D M A. It's
Speaker 1: not clear it's causing a release of serotonin, and it's
Speaker 1: probably binding to all fourteen of the serotonin receptors, not
Speaker 1: just to A. And it doesn't require to A to reopen.
Speaker 1: And so it might be that, you know, to stagger
Speaker 1: not only drugs that have different durations of critical period.
Speaker 1: So for example, if you want to on ramp somebody
Speaker 1: who's had a very very serious horrible, maybe complex PTSD
Speaker 1: and facing the traumatic memories all at once is too
Speaker 1: much for them, So maybe we want to start gently
Speaker 1: with them with some I'm just making this up, but
Speaker 1: this is what our newer data is starting to suggest
Speaker 1: that we want to start looking at the possibility of
Speaker 1: combining maybe some short acting, some micro doses, some ketamines
Speaker 1: early on, just to loosen things up, and then as
Speaker 1: the patient gets more comfortable, kind of do the longer
Speaker 1: trips that go deeper and then sort of stagger on
Speaker 1: top of that the big, big trip at the end.
Speaker 1: And that could potentially allow us to mix and match
Speaker 1: so that we can do the most work over a
Speaker 1: long period of time, but also give people breaks and
Speaker 1: also give people an opportunity to wait in if they're
Speaker 1: not ready to be kind of thrown out the deep
Speaker 1: end of the pool. Let's take a break here and
Speaker 1: go to an ad. Is there a limited number of
Speaker 1: times that one could use m d m A or
Speaker 1: these other drugs in order to open up this critical period?
Speaker 1: You know, listeners of this podcast, numerous episodes, I've expressed
Speaker 1: my great sadness that m d m A, which was
Speaker 1: such a wonderful drug in my life when I was
Speaker 1: in my thirties and forties and mostly using it with
Speaker 1: my romantic partner or with a close set of friends
Speaker 1: only a couple of times in a rage setting. Just
Speaker 1: doesn't really seem to work for me much in the
Speaker 1: last and fifteen years, And I'm wondering, is there only
Speaker 1: so many times you can use and the mail the
Speaker 1: others to open that critical period. I mean, we don't
Speaker 1: really have hard data on that. What I will say
Speaker 1: is that I have an idea that there's gonna be
Speaker 1: interactions between them. So for example, there's one clinical study
Speaker 1: in humans that shows that if you don't take people
Speaker 1: off their S s R I medications so they're Prozac
Speaker 1: or any of the drugs in that class, then the
Speaker 1: M d M A stops working. And that sort of
Speaker 1: makes sense because if the idea is that when you're
Speaker 1: blocking the serotone and transporter, M d M A actually
Speaker 1: has to sit in the same bonding pocket. So if
Speaker 1: the prozac is in there blocking it away, then it's
Speaker 1: possible that that interferes with M d m AS ability
Speaker 1: to get into that same pocket and cause the same
Speaker 1: remarkable consequences. But what's more than that is is that
Speaker 1: there's some older literature suggesting not with s s RRI,
Speaker 1: but with older generation antidepressants like tricyclicant and m a
Speaker 1: O wise that what is happening. The reason that there's
Speaker 1: this delay between when you start taking the antidepressant and
Speaker 1: when you start to feel the effect is that the
Speaker 1: real effect of the drug might not be increasing the
Speaker 1: amount of serotonin that's available in the synapse itself, but
Speaker 1: that by increasing the basil levels loading around the neuron
Speaker 1: serotonin that triggers in the cells that are normally receiving
Speaker 1: the serotonin signal to pull in some of those serotonin
Speaker 1: receptors and sort of downregulate the number of receptors that
Speaker 1: are in the membrane. So sort of like if you've
Speaker 1: got a bunch of microphones out into an arena and
Speaker 1: everybody in the arena is screaming, maybe you pull a
Speaker 1: couple of those microphones in so that it's not so
Speaker 1: loud anymore. So that's kind of one early idea about
Speaker 1: how antidepressive drugs were working, and there is some suggestion
Speaker 1: that this could also be happening for LSD and psilocybin
Speaker 1: as well. So I could potentially formulate at least a
Speaker 1: hypothesis about why m d M A might stop working
Speaker 1: if you're also doing a lot of other psychedelics and
Speaker 1: or taking prozac or any of these other antidepressive drugs,
Speaker 1: because they're sort of including each other's mechanism, Which is
Speaker 1: why I think it will be useful to develop an
Speaker 1: arsenal of drugs that are doing this with lots of
Speaker 1: different receptors. Right, So maybe I begin it's going to
Speaker 1: help for somebody who has already kind of maximally tuned
Speaker 1: the serotonin receptors. So is it a matter that does
Speaker 1: not one developed? I mean, even like I think in
Speaker 1: my case, I never did the antidepressants, and I have
Speaker 1: not been. I've been an occasional user of the psychoelics
Speaker 1: and DMA for decades, but never a frequent user. I mean,
Speaker 1: is there an element in which one does develop a tolerance?
Speaker 1: Just going back to that issue, if one's using this
Speaker 1: drug in the psychotherapy, right in the proper setting, in
Speaker 1: order to open up this critical period and deal with
Speaker 1: the past traumas PTSD or I was talking about psilocybin
Speaker 1: and depression or whatever it might be, and you make
Speaker 1: so progress. But I mean, obviously we sometimes see there's
Speaker 1: some research suggesting that when you do this, a one
Speaker 1: off can provide a real cure, right, not just a palliative,
Speaker 1: but a cure. Can there be value in our possibilities
Speaker 1: in terms of doing this two times, five times, ten times,
Speaker 1: twenty times, or is it kind of gonna peek out,
Speaker 1: like if it doesn't take the first time to do it,
Speaker 1: the second time, I got to do something else. Yeah, So,
Speaker 1: I mean there are already trials where I think in
Speaker 1: Europe MAPS is running some trials for complex PTSD doing
Speaker 1: sort of multiple rounds of m d m A. But again,
Speaker 1: because of this issue of tolerance, again, it's going to
Speaker 1: be really important to understand the mechanism because it's probably
Speaker 1: going to be the case that we're going to need
Speaker 1: to fine tune the dosing regiment so that we're not
Speaker 1: giving new m d M A before the critical period
Speaker 1: that we open is already closed back up again, so
Speaker 1: that we can sort of maximally extend the amount of
Speaker 1: time that the person can do the psychotherapy work without
Speaker 1: running into tolerance issues from staggering them too close to
Speaker 1: each other. But again, also this is going to be
Speaker 1: a case for trying to understand the mechanism, because one
Speaker 1: of the next follow up questions that my lab is
Speaker 1: really pursuing is, Okay, you know, we know that they're
Speaker 1: all working at different receptors. We have some hint that
Speaker 1: the next step, which is the biochemical signaling that comes
Speaker 1: after that, is also not the same for all of
Speaker 1: the different drugs. And so what's the next, next next step,
Speaker 1: what's the thing, what's the last final common denominator that
Speaker 1: brings all of these psychedelics into the realm of being
Speaker 1: able to be these master keys for critical period reopening
Speaker 1: and can we target that directly without melting the brain
Speaker 1: or causing seizures or causing a person to lose all
Speaker 1: of their memories. As we get a better handle on
Speaker 1: how these things are working, we can start to do
Speaker 1: a better job of designing trials with the drugs that
Speaker 1: we have, but then also learning from those mechanisms to
Speaker 1: know what are the limitations and what are the other
Speaker 1: things downstream that we could potentially boost to stop for example,
Speaker 1: of tolerance or maybe reverse if the tolerance doesn't end
Speaker 1: up being part of the mechanism for how the drugs
Speaker 1: are curing. And I think that the tolerance issue really
Speaker 1: is probably going to be more relevant to the non
Speaker 1: context dependent anti depressive properties of these drugs, which are
Speaker 1: going to be separate from critical period opening. And I
Speaker 1: think that critical period reopening is going to end up
Speaker 1: being the explanation for these cures, whereas the anti depressive
Speaker 1: properties are going to be more about the palliatives. And
Speaker 1: we can already see that a little bit in the
Speaker 1: clinical trial. So if we compare the way that the
Speaker 1: New England Journal of Medicine psilocybin versus SSRRI for depression
Speaker 1: trial went, you know, basically they used the psilocybin the
Speaker 1: same way that we give prozac, right, and so they
Speaker 1: were given the drug monitored for you know, bad side effects,
Speaker 1: but psychotherapy wasn't you know, a big component of it.
Speaker 1: And what they saw is is that the effects of
Speaker 1: um psilocybin on depression were very similar to s s RI,
Speaker 1: not worse, but not dramatically better either. Whereas the MAPS
Speaker 1: trial that was published in Nature Medicine last year, that one,
Speaker 1: you know, the the whole approach was this is an
Speaker 1: adjunct therapy and the context is psychotherapy. And in that case,
Speaker 1: even though we still have issues around controls and direct comparisons,
Speaker 1: the ability to cure the PTSD compared to ss RISE
Speaker 1: or compared to just psychotherapy RAP alone seems to be
Speaker 1: remarkably improved. So cool. At your lab at John's Hawkins,
Speaker 1: you have a project called FATHOM p h A t
Speaker 1: H O M. So what does that stand for and
Speaker 1: what's it about? What are you trying to accomplish there
Speaker 1: beyond what the research you've described so far. Yeah, so
Speaker 1: that stands for psychedelic healing adjunct therapy harnessing opened malleability.
Speaker 1: That came up with that in a dream, and I
Speaker 1: loved it because I love this idea that when people
Speaker 1: have really great m d m A experiences, they call
Speaker 1: it oceanic boundlessness. And I love the FATHOM as like
Speaker 1: a metaphor for that oceanic boundlessness. And basically, we're taking
Speaker 1: the unfathomable, which is cures for some of these brain diseases,
Speaker 1: and making them fathomable again. You know, that's sort of
Speaker 1: the dream that we are hoping. So the FATHOM project
Speaker 1: is really just our intuition that based on the fact
Speaker 1: that all of the psychedelics, whether they're empathogenic or not,
Speaker 1: or reopening the critical period, that these are the master
Speaker 1: keys for unlocking all critical periods. And that that's true,
Speaker 1: then the number of brain disorders and even probably non
Speaker 1: brain disorders. So I have an idea about curing allergy
Speaker 1: and curing stutter and curing stroke would be remarkably increased
Speaker 1: if it's true that these are the master key for
Speaker 1: unlocking critical periods that neuroscientists have been looking for for
Speaker 1: almost a hundred years. And the project is really everything
Speaker 1: from the basic research that we are doing to try
Speaker 1: and convince ourselves that they are in fact the master key,
Speaker 1: all the way up to human clinical trials for stroke
Speaker 1: that we are getting we're revving up to do and
Speaker 1: potentially in the future looking at what other ways that
Speaker 1: we can understand the brain using psychedelics. So with stroke,
Speaker 1: for example, obviously with m D m. A was talking
Speaker 1: about psychotherapypy with strokes once talking about physical therapy and
Speaker 1: reopening that critical period. And do you imagine that somebody
Speaker 1: is subject to a stroke and gets partially paralyzed, that
Speaker 1: they would be able to go through these sessions. I mean,
Speaker 1: maybe not just one, but to do them two, three
Speaker 1: or four times a year to keep returning to that
Speaker 1: critical period with a physical therapist and delving more deeply
Speaker 1: into it. Absolutely, So that's the dream. Basically, what we
Speaker 1: think is is that most people who have a stroke
Speaker 1: now get some physical therapy, but it's not the sort
Speaker 1: of intensive motor practice that they need to get full recovery.
Speaker 1: And so most people get partial recovery. They compensate, you know,
Speaker 1: they learn how to button their pants with the other hands,
Speaker 1: They learn how to use their whole hand instead of
Speaker 1: their fingers to manipulate objects. But you know, what we
Speaker 1: want is full recovery of normal levels of motion. But
Speaker 1: this is just for motors strokes, but you know, all strokes.
Speaker 1: And the ideas is that if we can pair the
Speaker 1: psychedelic and the way we're imagining it right now is
Speaker 1: is that the optimal way to pair it is not
Speaker 1: to pair it to practicing the specific motion that you
Speaker 1: are trying to get back, so like reaching for your
Speaker 1: cup or something, but that we should pair it with
Speaker 1: some sort of video game so that you are taking
Speaker 1: full advantage of the fact that psychedelics seem to put
Speaker 1: people into this mode of play like behavior, or non
Speaker 1: goal directed behavior, and that practicing motor in that sort
Speaker 1: of non goal directed manner paired with psychedelics should maximally
Speaker 1: restore the old ways of learning motor behaviors that you
Speaker 1: had from when you were a child, and that that
Speaker 1: will help restore more function after the stroke critical period
Speaker 1: has closed. And could you imagine virtual reality types of
Speaker 1: machinery also playing a role in his stuff. Yeah. So
Speaker 1: our collaborators on this project are Steve Zeiler and John Krakauer,
Speaker 1: and they have been developing not exactly virtual reality, but
Speaker 1: a video game that they can manipulate. The patient manipulates
Speaker 1: their arm and a dolphin on the screen kind of
Speaker 1: swims around. And we love that interactive video game aspect
Speaker 1: of it that they could play while they were on
Speaker 1: psychedelics and for several days after the acute effects have
Speaker 1: worn off, continue to practice with that to kind of
Speaker 1: trigger the right kinds of mine. So that's exactly the
Speaker 1: idea that we are pursuing. Fascinating. I mean, I read
Speaker 1: that you know, years ago your interests and maybe still
Speaker 1: you had a strong interest in autism, and I guess
Speaker 1: with autism there was for quite a while, maybe still
Speaker 1: the notion that it's grounded in some sort of chemical imbalance.
Speaker 1: But how do you see this work relating to autism
Speaker 1: and trying to help people with it. Yeah, So when
Speaker 1: I was a graduate student, you know, my thesis was
Speaker 1: something called the M blu R Theory of fragilects and Autism,
Speaker 1: and it was basically testing this idea that what causes
Speaker 1: most of the impairments that we see in fragile X,
Speaker 1: which is a subtype of autism, are really an imbalance
Speaker 1: of this signaling that happens through another type of receptor
Speaker 1: called the m gluar and the protein that's missing in
Speaker 1: in fragile x. And we were very excited. We know,
Speaker 1: we did all these studies in animals and then we
Speaker 1: were able to show that if we turned down the
Speaker 1: m glure signaling, then we could restore normal function in
Speaker 1: a bunch of different domains in mice. And we did
Speaker 1: those studies and then twenty six other pre clinical labs
Speaker 1: replicated those findings, and all of the big drug companies
Speaker 1: got so excited. They were like, this is it. We've
Speaker 1: got the mechanism. Hundreds of millions of dollars were invested
Speaker 1: in clinical trials, and to the disappointment of the whole field,
Speaker 1: those clinical trials did not show clinically relevant improvements in
Speaker 1: human patients with autism. And I think that some of
Speaker 1: the people after those trials sort of dismissed them and said, well,
Speaker 1: you know, a mouse isn't human, and that's why they
Speaker 1: didn't work. But the authors themselves of the clinical trial
Speaker 1: studies wrote a follow up paper sort of discussing, you know,
Speaker 1: what they thought might have happened and what might be
Speaker 1: some future directions. And one of the things that they
Speaker 1: mentioned is is that all of the pre clinical studies,
Speaker 1: all of the mouth studies, were done very early in development,
Speaker 1: So either from genesis in the case of genetic manipulations
Speaker 1: or even just the pharmacological manipulations, all happened in juvenile
Speaker 1: animals before a critical period for social reward learning would
Speaker 1: be closed. And granted, these studies were done before we
Speaker 1: had discovered this critical period. So I'm not you know,
Speaker 1: pointing fingers or anything, but to me, that's very interesting
Speaker 1: because what it suggests is this that maybe what we
Speaker 1: need to do with autism is go back and test
Speaker 1: that biochemical imbalanced idea, but in this time, instead of
Speaker 1: giving the drug by itself, we pair it with reopening
Speaker 1: of the social critical period, and under those conditions of
Speaker 1: restoring the imbalance in the open state of the critical
Speaker 1: period will allow patients to learn from their social environment
Speaker 1: in the way that they missed out on early in development. Wow,
Speaker 1: So do you actually have a study underway of trying
Speaker 1: to look at opening up the critical period with people
Speaker 1: with autism. We are starting in animals because I want
Speaker 1: to move carefully on this because one of the things
Speaker 1: that we know about autism is that the autistic mice
Speaker 1: do seem to have there's some indication that their critical
Speaker 1: periods don't close normally and that they have hyper plasticity.
Speaker 1: Before we'd be willing to jump into human clinical trials
Speaker 1: for that, I would want to make sure that a
Speaker 1: it works in mice, but also that it's safe, right,
Speaker 1: because especially with schizophrenia and autism, there's been a lot
Speaker 1: of very well justified hesitation to jump in with psychedelics
Speaker 1: in case there's overlap between what causes tis UM and
Speaker 1: the same mechanisms that the psychedelics are triggering. But I
Speaker 1: also want to just say that while this sounds like
Speaker 1: I'm making one big rosy blanket, I also just wanna
Speaker 1: caution that these are very powerful drugs, right. They have
Speaker 1: incredible potential. But if we don't understand how long they're
Speaker 1: lasting and what the impacts of the context are on
Speaker 1: our ability to change things. Then I think they can
Speaker 1: be dangerous and used for ill by bad actors as well.
Speaker 1: I'm sure you've heard this analogy before. But of course
Speaker 1: we know that Charles Manson was giving members of his
Speaker 1: group LSD and indoctrinating them into his family. And this
Speaker 1: is not surprising to me as I think about how
Speaker 1: easy it is to manipulate children, how important it is
Speaker 1: to safeguard children from being exposed to certain kinds of things,
Speaker 1: and if we're really returning people to this childlike state
Speaker 1: of vulnerable city, we also want to make sure that
Speaker 1: we protect ourselves from exposing ourselves to the wrong kinds
Speaker 1: of people. Yeah, yeah, no, I mean that definitely makes sense.
Speaker 1: I think you're exactly right in terms of the negative
Speaker 1: possibilities in terms of cults and all this sort of stuff.
Speaker 1: So gl I typically ask my guess how and why
Speaker 1: they got into this line of work, And I've read
Speaker 1: that you know, you come both your parents were doctors,
Speaker 1: and you come from a family full of doctors and scientists.
Speaker 1: But what can you share with us about your own
Speaker 1: use of psychedelics and how it may have impacted the
Speaker 1: ways you think about the research you're doing. Now. Yeah,
Speaker 1: as a scientist, I'm a little bit hesitant to talk
Speaker 1: about any of this kind of thing, but I will
Speaker 1: just say that I think you would find that a
Speaker 1: larger percentage of neuroscientists than you might imagine first became
Speaker 1: interested in studying the brain because of psychedelics. And so
Speaker 1: I can tell you that my interest in this subject
Speaker 1: really started with a class that I took in college.
Speaker 1: My professor was Cynthia Kon, and she taught this class
Speaker 1: called Drugs, Brain, and Behavior. And about half of the
Speaker 1: class where you know, psychonauts who just wanted to know
Speaker 1: what they were putting in their bodies, and the other
Speaker 1: half were sort of eager beaver medical students who wanted
Speaker 1: to get, you know, a leg up on pharmacology. And
Speaker 1: when I saw the serotonin molecule picture right next to
Speaker 1: the LSD molecule, I had sort of an epiphany that
Speaker 1: this was going to be the way that we were
Speaker 1: going to be able to answer the hard problems of neuroscience.
Speaker 1: What is consciousness? How is it that we know the world,
Speaker 1: what exists in the world? The sort of metaphysical problems
Speaker 1: that I think most neuroscientists start out with and eventually
Speaker 1: give up on because they realized that they're very hard
Speaker 1: and we're never going to be able to have sort
Speaker 1: of mechanistic detail on them. In that moment, in that class,
Speaker 1: I had the idea that psychedelics would really be the
Speaker 1: tool to help us answer those big questions. And I
Speaker 1: continue you to feel that, although I'm really excited that
Speaker 1: now seems to be the time to be able to
Speaker 1: do it, because I think when I was in undergrad
Speaker 1: we were still very much in the middle of the
Speaker 1: war on drugs, and I mean, obviously your listeners don't
Speaker 1: know a lot about that, but this shift that we've seen,
Speaker 1: even in the last three or four years, it's not
Speaker 1: complete yet. I mean, I'm still struggling to get funding
Speaker 1: from the nih for this kind of research because even
Speaker 1: though the higher ups are saying, yes, we're interested, there's
Speaker 1: still a lot of minds that need to be changed
Speaker 1: to see their potential. But for me, beyond the clinical
Speaker 1: aspects of it, I really am still incredibly motivated by
Speaker 1: the opportunity I see to use these as tools for
Speaker 1: discovering answers to the big questions like consciousness, right, And
Speaker 1: when it comes to your reticence about talking about whether
Speaker 1: or how what you might have done, it is part
Speaker 1: of that about needing government funding, or part of about
Speaker 1: fear about the climate shifting, or part of it that
Speaker 1: you're not yet a senior professor with a big chair
Speaker 1: and all this sort of stuff. What holds you back
Speaker 1: in that? I mean, I think it's a little bit
Speaker 1: of all of those things. But also people often tend
Speaker 1: to think of science as a metaphysics, you know, a
Speaker 1: certain this is what's in the world, right, And I
Speaker 1: don't think of science that way. I think science is
Speaker 1: an epistemology. In other words, science is how do we
Speaker 1: learn the world? What are the methods we use for
Speaker 1: discovering what is and isn't in the world. And there
Speaker 1: is an older scientific tradition where it was acceptable to
Speaker 1: know the world through direct personal experience. I mean, there
Speaker 1: have been Nobel Prizes one for that kind of and
Speaker 1: equals one science, right, but especially in neuroscience, that is
Speaker 1: not something that is necessarily thought to be good science.
Speaker 1: And especially this might be true with psychedelics because they
Speaker 1: do have this no edic property of you know, when
Speaker 1: you take them. You have this sense that like, oh okay,
Speaker 1: now I really really know, like everything I knew before
Speaker 1: is not as true as what I know now because
Speaker 1: of the psychedelics. And I think this leads some people
Speaker 1: to narcissism in science. I think it has the potential
Speaker 1: to lead to sort of confirmation bias and um So,
Speaker 1: you know, at least in my own research, I have
Speaker 1: been very very um careful and nervous to over extropically
Speaker 1: personal experiences to the research because I think, especially with psychedelics,
Speaker 1: confirmation bias is a real problem. I can't say that
Speaker 1: I've fully succeeded in that because you know, but nevertheless
Speaker 1: it's something I worry about. Well, well, I've just learned
Speaker 1: so much from our conversation as well as preparing for
Speaker 1: our conversation. Thanks so much for joining me on Psychoactive.
Speaker 1: I think it's only a matter of short time before
Speaker 1: you're gonna be another one of those big shot some
Speaker 1: psycholic studies with your own chair, and you already have
Speaker 1: your huge program. You're already making quite a name for yourself.
Speaker 1: But this is fascinating. I really am curious to see
Speaker 1: where your research goes into other areas. So thanks so
Speaker 1: much for joining me on Psychoactive. My pleasure and thank
Speaker 1: you very much for having me. If you're enjoying Psychoactive,
Speaker 1: please tell your friends about it, or you can write
Speaker 1: us a review at Apple Podcasts or wherever you get
Speaker 1: your podcasts. We love to hear from our listeners. If
Speaker 1: you'd like to share your own stories, comments and ideas,
Speaker 1: then leave us a message at one eight three three
Speaker 1: seven seven nine sixty that's eight three three psycho zero,
Speaker 1: or you can email us at Psychoactive at protozoa dot com,
Speaker 1: or find me on Twitter at Ethan Natalman. You can
Speaker 1: also find contact information in our show notes. Psychoactive is
Speaker 1: a production of I Heart Radio and Protozoa Pictures. It's
Speaker 1: hosted by me Ethan Nadelman. It's produced by Noam Osband
Speaker 1: and Josh Stain. The executive producers are Dylan Golden, Ari Handel,
Speaker 1: Elizabeth Geesus and Darren Aronofsky from Protozoa Pictures, Alex Williams
Speaker 1: and Matt Frederick from My Heart Radio and me Ethan
Speaker 1: edelmid Our music is by Ari Blucien and Especial Thanks
Speaker 1: to a Brio, s f Bianca Grimshaw and Robert BB.
Speaker 1: Next week I'll be talking with Plaul Armentano, Normal's longtime
Speaker 1: deputy director about marijuana and driving. If we didn't have
Speaker 1: that linear correlation, we wouldn't have per SE levels for alcohol.
Speaker 1: In fact, per SE levels for alcohol only date back
Speaker 1: about forty or fifty years. The reason we don't have
Speaker 1: these levels for cannabis or opioids or a number of
Speaker 1: other drugs that we don't impact driving performance is because
Speaker 1: there is no linear correlation. Subscribe to Cycoactive now see it,
Speaker 1: don't miss it.