Hey, it's like if you're with a quick note today We have the second installment in the series where we just sort of let ourselves fall into a conversation between our own senior correspondent Molly Webster And a scientist who's working on the front edge of something if not exactly news Something deeply and delightfully new. So here we go Listening to radio lab from WNY I Don't know about you, but I found being a teenager and you know going into puberty very difficult You know I I was bullied by the mean girls the popular girls at school and had to eat lunch by myself And I remember having a tearful conversation with my mother and she was like don't worry It'll pass you think that this is the whole world right now But in a few years you'll be off in the bigger world and you'll see that there are a lot more people and you'll fit in better And it'll be fine. I'm Molly Webster This is radio lab and that was ghoul dolan a neuroscientist and former teen But unlike maybe the rest of us former teens ghouls very familiar teenage struggle We end up at the center of her scientific work and lead to new ways of seeing the moments in our lives when our most basic habits and behaviors emerge And then get locked in and it all starts with something called critical periods Okay, so for like us, you know yokeles over here like what is a critical learning period? Yeah, so critical periods are windows of time when the brain is especially sensitive to its environment And it can learn really well and really strong from that environment Probably the best way to understand that is to think about the first critical period that was described I think a lot of people have heard of it.
It's imprinting behavior in geese. So this is so cute We did a story an episode on it. Yeah, so yeah, so Conrad Lorenz what he noticed is that within 48 hours of hatching a little geese will Well Gosling I don't know gossling Anyway, yeah, well form a long-lasting attachment to whatever is moving around in their immediate environment And so typically this is their mom But if the mom isn't there it could be another mom or if it's you know Conrad Lorenz it could be a scientist But then after that 48 hour time window is over They can be exposed to all kinds of things in their environment and they won't form that lasting and attachment So that little window of time where they're so sensitive to their environment and they can form this lifelong attachment is what he coined the phrase critical period and when was that discovered so that was in I think 1935 and then since 1935 we've discovered dozens of other critical periods Well, there's critical periods for language. There's critical periods for vision.
There's critical periods for touch for you know motor learning There's there's critical periods basically for everything that the brain has to learn that isn't encoded in your genes And do we associate those critical periods with being a baby? Yes, mostly it's I mean not just babies They're you know different windows depending on what you're trying to learn at the time So you know vision the critical period peaks around three or four years old by five or six It's closed language stays open probably six seven eight and then it's closed Motor learning is a little bit longer because you're still learning a lot of motor things pretty far along and then you know neuroscience often makes me feel like I just started falling behind it like Three months old because you're just like oh that window closed and that window closed and that window closed I'm like I'd like to think I'm 40 and the world is still my oyster But perhaps not yeah, well, I mean definitely when I've talked about this with some people they get a little offended Because they're like what do you mean? I'm open-minded I'm open-minded and I'm 40 and it's like yeah You're open-minded, but you're not a sponge the way that a child is a sponge right like if you ever watch a kid trying to get out the door on a Snow day, it's brutal, you know like they are noticing everything. It's like shoes what shoes look at this Does bunny you know every single leaf is like a magical kingdom full of Possibility and they're just noticing it all and so you know they need to close because it's not it's not very adaptive to be always in that open vulnerable state forever And if you're trying to make your way through a saber tooth tiger infested area It's probably better to be you know a habit-based efficient, you know, and you're like oh look at the flower Oh look at the butterfly.
I love your tooth It's awesome But the ability to reopen critical periods has been something that neuroscience has been looking for for almost a hundred years because We realized that you know the reason that we're so bad at curing diseases of the brain is because by the time we get around to Fixing the underlying problem the relevant critical periods have all closed. Well, this is like creating such a feeling of like urgency in me Yeah So critical periods are great for learning and learning fast They make a super spongy and absorbent to the world around us But the fact that they close makes it hard to relearn something we've lost or to unlearn something that's getting in our way But ghoul in her first lab at Johns Hopkins University actually uncovered a whole new way of thinking about that problem And weirdly it all comes down to peer pressure my postdoc who had studied very early brain development was really interested in studying You know how social behavior changes over maturation and he was like what if critical periods is the basis of this change in peer pressure behavior in juvenile's versus adult? And at first I was like that's kind of a boring project really and he was like no no I really want to do this development thing and then I was like well, you know, I Do I do remember being believe it's a teenager, you know, maybe there's something here you were peer pressured into peer pressure Yeah, basically Yeah, I mean anyways just to take it back a second I mean part of the reason that I think I've gone back and tried to interpret why did I struggle so much with fitting in when I was in Middle school and you know if I really think about it It's because when I was younger I was so obsessed with being in the right in group and knowing the exact right shade of acid wash jeans The cool kids were wearing and I had this idea that maybe we care so much more about Who's in our social group and our social environment because we're learning from our social environment much more when we're younger than when we're older And so that was sort of my own personal intuition about why there might be such a thing as a critical period for social reward learning But of course in the human literature, they can't do, you know a comprehensive Study of you know one type of social behavior across 15 different ages You know looking at hundreds of people at each age it would cost way too much money But I knew that we could do that kind of experiment in mice So go on your team they get a bunch of mice at all different ages and they observe them very very closely and she Basically confirms sort of what we see anecdotally in humans that teen mice pay attention to their friends more They learn from their friends more but then they opened the tiny mouse brains And what I saw is that mice just like humans have oxytocin this sort of feel-good chemical that's released when we're around friends or loved ones And they saw that the neurons in the teen mouse brains were more susceptible and sensitive the oxytocin And so it seemed like oh, this is a biological Neurological critical period and then right away we were like okay We need to figure out a way to reopen it wait So they reopen yes And that's interesting because one of the earliest ways that people figured out that you could reopen critical periods was Deprivation so visual deprivation for example can reopen visual critical periods auditory deprivation can reopen auditory critical periods sensory deprivation can reopen touch critical periods It's just not a very clinically useful way of doing it right like it's just not like how long do I have to be Molly's over here looking at her calendar Yeah, so we were we were looking around for different ways to reopen it and we knew the MDMA was a psychedelic drug that was special and different from Most other psychedelics because it had this ability to induce pro-social behavior You know kids were taking these these drugs and going to raves and doing you know 60 person cuddle puddles, but also yeah I mean it is it's a very powerful Powerful drug and it does have these very profound effects on people so then we thought well if MDMA is able to induce a massive release of oxytocin which there was some evidence from other labs showing that we thought maybe this would be a Really cool way to reopen this critical period by triggering this massive oxytocin release that can prepare the neuron to learn from its social Environment again So they go back to the lab back to the mice who this time are gonna go on a little trip in this experiment We were giving the MDMA and then waiting for two days So they're no longer actively tripping they're no longer actively cuddle puddling or doing anything like that Would you like peek in with like a secret telescope to to see what their behavior was like in those two days? No, we could have but we didn't okay I don't know if you've seen people on psychedelics, but unless there's a DJ, you know They can look very boring on the outside right?
I mean I'm not sure maybe the mouse got acid wash jeans or something Unbeknownst to us so no so it wasn't like that basically what happened was is that then they had a how much do you care about social interaction? Quiz essentially like we had we tested them on can you learn from your social group again? So we say okay, here's two new types of betting and we want you to tell us which one you like better by how much time you spend on them And when we did that test these were adult animals, but the ones that had gotten MDMA two days later when they go into the bedding It's like oh, I like this bedding because I I remember that all my buddies like this bedding and that's where I found my buddies is on this Bedding so I like this bedding not this other bedding right when they received the MDMA in a social context with their friends suddenly They all cared right like they suddenly they were learning from their social environment again as if they were teenagers And what Guilhert team saw is that the adult brains on MDMA they actually went back to that sensitive teenage-like brain state So can I tell you what we were wrong about there? I don't know if I told you this right sure yeah So at the end of that paper in 2019 we were like okay great.
We understand this now It's because MDMA is prosocial But we also knew that MDMA belonged to this larger group of compounds that are all psychedelic right and so I was like Let's just test it with LSD and suddenly all of the animals who had received LSD were also Doing social reward learning like they were juveniles again, and I was like okay. This is weird I don't understand why this is because you know nobody's doing LSD and then you know doing a 30 person cuddle cuddle You know people do LSD don't have this like acute prosocial effect that MDMA has right so it's that's strange Let's test a couple of others in case so then we did it with psilocybin and we got the same thing and then we were like okay Well, what about like ketamine and it did it and basically all of the psychedelics are doing it like the fact that it's a drug that Induced to social behavior is not why you're seeing social results. It's about the it's about the class of drugs of psychedelics That's right. That's right.
It's the psychedelics part of it not the prosocial effects of MDMA that make it able to reopen this critical period You know when I first started working on psychedelics, but this was about 10 years ago The fad was look everything cool that psychedelics do you really have to study in a human There's no way that you're ever gonna be able to get at that mystical experience that what is a mouse seeing God even look like? You know, you're just not gonna be able to get to the heart of the cool stuff if you study it in animals and I think that this critical period explanation is the first one where we can really challenge that worldview and what I think it is that this Seeing God this mystical experience is really just what it feels like to reopen critical periods Just to put that in context It's like a dude tripping in a corner is in a way having the same experience as like a wide-eyed baby soaking up their world or a teenager Who cares so much about what everyone else thinks of them and it's not just that they're experiencing in the same way It's that there's an underlying deep biological Mechanism that's being shared in all those situations and if you can tap into that mechanism There are some very real-world practical things that you might be able to do Which we'll get into right after this break Hi, Lulu here and this episode is sponsored by BetterHelp. May is Mental Health Awareness Month And as someone who reports on mental health who likes talking to people about their mental health and what they look to in science in the natural world in Faith in friendship, but wherever it may be to help guide them through the rough patches of life I just wanted to take a moment to say what seems to help people turn corners find relief get out of ruts and even flourish is having Someone with you as much as we can feel private about our mental health struggles. You do not have to go it alone So this may why not treat your mental health to a buddy and who better to talk to and a fully licensed mental health therapist with over 30,000 therapists available better help has someone you can talk to available at pretty much anytime that's convenient for you At the push of a button and because finding help you need often depends on the therapist claim vibe or rest assured It would better help you can switch providers at any time Remember truly your mental health matters and you don't have to go it alone find support You need anytime with better help sign up and get 10% off at better help calm slash radio lab.
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We are back in the saddle with neuroscientist Ghoul Dolan She's been telling us about how psychedelics can reopen critical periods in the brain And where it goes from here in a way just gets more practical because I think we've all been hearing about studies in which psychedelics are curing various afflictions so like MDMA is helping with PTSD or psilocybin aka magic mushrooms can help with depression and Ghoul says that she thinks her study the one that she did with mice that it might be able to provide a clue about how those treatments are doing what they do if We gave MDMA in a social context than it was able to reopen the critical period But not if we gave MDMA in an isolation context So in the case where they were by themselves having MDMA they did not reopen their social critical period context matters, right? It's not like people are going to Burning Man and just having a dance party and coming back cured of their PTSD It's the right if you give MDMA in the right context So if you pair MDMA with therapy then you get these remarkable results. That's very interesting that in a way It's not the psychedelic that I mean it is this the presence of the psychedelic is allowing something else in the brain like an Experience or whatever to have an action. No, so let me just unpack that in two different ways Because I do think that this is to me where the crux of the debate right now is I think there's sort of I meant who knew The crux of the debate seems to be you know What I call the biochemical imbalance model of psychiatric illness and to the learning model And so the biochemical imbalance model is it basically says if you are depressed It's because of a biochemical imbalance and serotonin and all we have to do to make you undepressed is restore that balance, right?
The problem is is that that approach has only provided symptomatic cures right so people who are on SSR eyes, you know when they come off of them They go back to being depressed people who are on well butrin when they go off of well butrin they go back to smoking and people who follow that model Find that to be an acceptable solution But the psychedelics they have these remarkable results where people instead of taking you know one a day for years and years and years The MDMA assisted psychotherapy trials. It's three pills total and Those no longer adaptive habits become available for relearning for updating to the current circumstances and six months later The underlying condition is resolved. So what people describe with psychedelics is it's like it was 20 years of therapy in one day And I think that our critical period idea really provides an explanation It's not just that something is happening at the receptor level that is rebalancing a biochemical imbalance It's that it that thing that's happening is enabling a Reconfiguration of all of the synapses that are relevant to the trauma and that is the cure. It's the reconfiguring.
That's the cure It's the learning that's the cure Guul says that when you use a psychedelic in the right context It actually opens up the brain at a cellular level so that the neurons can reorganize themselves and in that reorganization They can create new patterns and new pathways that allow for learning and maybe even healing So really what these drugs do is create a window of opportunity How long was that period seemingly open for? This is probably the coolest part of this paper There's this proportionality between the duration of the acute subjective effects of the psychedelics in humans and okay The trip the trip the length of the trip the length of the trip is proportional the length of the trip in humans Is proportional to the duration of the open state that we can induce of this social critical period in mice So for example, kenamine keeps the critical period open for you know two days and then you know by a week It's closed. So let's I've been an MDMA keep it open for two weeks and it closed by three weeks LST keeps it open for three weeks closed by four weeks And then there's sort of a rock star psychedelic which most people haven't heard of called ibogaine and that the trip lasts anywhere from 36 to 72 hours Wow, okay, and ibogaine reopens the critical period for at least four weeks and we haven't tested the the closure We haven't found this everyone had to like go home for dinner and you're like we can't we can't test anywhere I mean, it's just sort of interesting because you think Even four days four days two weeks more than a month like are you just in those moments like vulnerable to Everything are like it just feels like the the next couple of weeks like solidly matter Yes solidly matter and solidly vulnerable so it's possibly a mistherapeutic opportunity But it's also possibly a time when we could do great harm to people because they're suggestible They're sort of vulnerable to information coming in the way that children are and then we've you know Kind of thrown them back into their lives and possibly re-expose them to whoever's been traumatizing them And that we could potentially lock in some some really bad things. It's funny.
It's yeah. I think about I mean recreational psychedelics use People are doing it all the time At least in my world and like now I just like want to be like Okay for the next two weeks if you could you know be careful or maybe go if you go take a yoga class If you really want to learn that that technique or something. I don't know it's just there the the vulnerability part of it feels um And vulnerability is it has such a negative connotation, but I do think it goes both ways of like it just you're vulnerable you're malleable You're open that feels like a double-edged sword. Yeah, to me these drugs are Extremely powerful medicines and we need to treat them with respect I you know really feel like if you see these drugs as powerful ways to restore You know that childlike sense of wonder and vulnerability In the two weeks after you do a psychedelic you should take care of yourself like you're four Right like don't expose yourself to anything that you wouldn't take your four-year-old to You know from my point of view as a neuroscientist maybe These psychedelics are master keys for unlocking all kinds of critical periods that are very precise Master key.
Yeah, right? All we have to do to change which critical period gets reopened is change the context So if you want to reopen a social critical period You give it in a social context if you want to open in a motor critical period You give it in a motor context, right? So maybe the rave is a great way to open a motor context critical period But not necessarily an inner directed PTSD kind of critical period Wow, okay, but you know when I first started talking about this master keys idea people were just like rolling their eyes Oh really? Yeah, oh for sure that your critical period is just a baby critical period It's not like the serious hardcore critical periods that matter clinically You know, you're just it's just easy to open because it's the door isn't closed that hard on that one anyway, it's like social Where mammals are social yeah, and we still care about social.
It's just you know social It's an emotion. It's not that hardcore critical period that would so the hardcore one is vision and Since we first started making the case that psychedelics are reopening this critical period There have been a couple of other papers from other labs showing that actually they can reopen Well, kenamine is the one that people have looked at but I think there's now another paper out about lsd suggesting that they can reopen ocular dominance critical period so the visual critical period can also be reopened But the most hardcore one is motor right so movement and this is the one that matters for stroke And just so you know Reopening this motor critical period after stroke has been you know a goal of clinicians and it's kind of where good ideas go to die right like People have been trying to do this for stroke for a long time because roughly a million americans a year get a stroke and half of them Are debilitated for life afterwards, right? They it's just it's just horrible 500,000 people a year are debilitated in the united states and stroke is you know much more common in other countries So it's a worldwide massive burden and just real quick Why is motor neuron like like the top of the mountain for critical periods? I mean we don't really understand how it happens But basically what we think is is that when the stroke happens the brain region that is encoding Let's say it's a hand movement that those neurons that are encoding that hand movement die And neurons in the in the motor cortex are not able to regenerate so once they're gone they're gone And so what we think has to happen in order to recover from a motor Injury is is that the nearby neurons that are encoding say the arm or the elbow or the upper arm Those neurons have to get repurposed and have to learn how to do finger even though they're normally doing elbow That's a hard thing because you know they've got a job already and they've been doing that job for 70 years potentially You know, that's right.
That's right. That's right. And so that's why we think it's so hard And right after a stroke if you want to reopen the critical period again So far the best way to do that is to give another stroke, which is not clinically useful, right? Like nobody wants to cure stroke by getting another stroke So the main thing that ghouls team is focused on right now is designing a clinical trial for stroke patients What they know is that generally after a stroke the critical learning window is open for about two to three months And then it closes So we think that after they've you know done as much as they can during that two months three months after the stroke with the physical therapy But they haven't recovered full-motion yet.
We can give them psychedelics and keep it open a little bit longer. Keep the PT going keep it going Actually though in the first version of this trial what we're going to do is we're going to take people who had a stroke over a year ago So their critical period is closed down hard and fast shut hard close And then we're going to try and reopen in those people and see what happens to their ability to Pair that that psychedelic with physical therapy this time instead of psychotherapy and say say your trial works That you see that if you have a stroke and I give you m dma and for two weeks we do stuff and you can gain motor neurons skills back that's great, but imagine That you don't gain all your skills back. So then you're like, okay I'm going to do m dma again keep the window open for two weeks So I get a month out of this right two doses I get a month where I'm open I'm wondering is if you hit a point where the m dma your brain's like used to it There is evidence that there is only so many times that you can take these psychedelics before they stop working in this way There's evidence you know anecdotally from Recreational users who estimate that you've got about 20 or 30 really big m dma trips And then you're done and it loses this magic after that. Yeah, it's it's like Makes me think that you know depending on how your stroke stuff comes out That I want everyone to save at least One m dma trip for themselves, you know for when they're older right right?
Yeah, I agree. I'm hopeful I mean we don't know this is this is really i'm speculating now Um, but if this is the case maybe you use up all of your m dma slots But you've never done ibigame and so you can still have an ibigame in reserve that you could tap into to reopen But you know this remains to be seen I sort of want to run out of here and i'm not sure if I want to do m dma with a therapist If I just want to do m dma and cut a look people for two weeks, you know Or if I just don't want to do m dma at all Like maybe go hide in the cave for a while I don't know for me personally the thing that I'm most excited about is you know If we're right about this master key business then what it means is is that there's a lot of other diseases that Psychedelics are not being explored for that really we should be thinking about right? So as a whole new avenue that will have implications for you know people with cochlear implants people with traumatic brain injury You know all kinds of other diseases that really right now we just don't have any therapy for This episode is reported by me molly webster. It was produced by the amazing sinu nana sambindan There's production help from me and tini broadwick in fact checking was by emily creaker I want to give a huge thank you shout out to ghoul dolan who's now at the university of california berkley and talk to me multiple multiple times Special thanks also go to charles phillip and david herman and a special shout out to raman nardu who is in the lab of ghoul dolan Is the postdoc we referenced earlier in the piece the one who said you know let's study peer pressure Finally if you want that spongy brain juice you should check out our newsletter It's got content extra content insider content fun pictures staff rex You can go to radiolab.org slash newsletter and sign up or check out the link on the show notes That's the show folks.
I'm molly webster. This is radiolab catch up later Hi, i'm david and i'm from baltimore maryland radio lab was created by jad obumra and is edited by soren wheeler lulu miller and lots of nasa Rr co-host dolan keef is our director of sound design our staff includes simon adler jeremy bloon becka bresler w herry fortuna david gable maria pause Gutierrez sinu nyanum sambindan matt keelty ani mikewen robeka laks Alex niesen saara cari saira sanbak areaan wack pat walters and molly webster our fact checkers are diane kelly Emily kreeder and natalie milled Hi, this is le from cleveland, ohio leadership support for radiolab science programming is provided by the gordon and bedding more foundation science sandbox a simon foundation initiative and the john templeton foundation foundational support for radiolab was provided by the alfred people and foundation