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How can a deeper understanding of mental health help us see our world, and ourselves, differently? Hosted by therapist Kurt White and journalist Mary Wilson, each episode of Unravelling explores a complex mental health topic with insights from both professionals and people with lived experience. Whether you're trying to make sense of the world or just the slice of it inside of your head, Unravelling is here to foster a more compassionate and informed perspective on life.
The content of this podcast is for informational purposes only and should not be considered medical advice. Always consult with a qualified health care professional for any health concerns. Take care of yourself out there.
Mary:Welcome to Unraveling. This is a podcast that sees the world through the lens of mental health. I'm Mary Wilson, a journalist.
Kurt:And I'm Kurt White, a social worker and psychotherapist.
Mary:And we have a really great episode for you today. And, Kurt, I know you are quite excited about the person that you got to interview.
Kurt:Yes. I'm I'm kind of out of my my gourd excited about it, actually. I I'm not this is I I really geek out. I'm as I say at the beginning, I'm a social worker and psychotherapist, but there's another lifetime where I'm a researcher in things like developmental biology, evolutionary genetics, and things like that. And so, you know, we've been doing some episodes on that.
Kurt:And I really had the hope that we could get our guest today on the program to talk about critical periods, what these are and how they work and what her research is.
Mary:And critical periods are these times when there's more plasticity in the brain and when it's more sensitive and receptive to learning new things.
Kurt:Yeah. Absolutely. I I think, you know, sometimes we think about, like, you know, the DNA is our genetic code, but then there's things that influence that. But maybe people who are not in the know don't necessarily think that sometimes there are particular windows of time when certain things have to develop, have the opportunity to develop, where our minds have very particular kinds of neuroplasticity that open and close. It's sort of like a formula, but it has to interact with the environment.
Kurt:How do they work? Could we ever use them for therapeutic benefit? That's the kind of stuff we're gonna get into today.
Mary:Yeah. Because it was once thought that when these critical periods ended, that was it.
Kurt:That was it. Right. Maybe
Mary:that's not the case.
Kurt:That's right. And that's what we're gonna hear her talk about today. Doctor. Gul Dolan, MD, PhD, is the professor and Renee and Bob Parsons Endowed Chair in the Departments of Neuroscience and Psychology, the Helen Wills Neuroscience Institute, and the Berkeley Center for the Science of Psychedelics at the University of California, Berkeley. She's the director of the Fathom Project, maintains a series of other academic affiliations at other major universities.
Kurt:She is widely recognized to be a pioneer and world leader in psychedelics research, having discovered a number of very important things about how psychedelics and critical periods work together.
Mary:And we hope you enjoy our conversation with Gul Dolan.
Kurt:Well, doctor Dolan, thank you so very much for joining us on Unraveling.
Dr. Dolen:My pleasure. Great to be here.
Kurt:So my hope today was that we could talk about some of your research and discoveries, which have been really interesting and exciting to me ever since I've heard about them. Now I I'm interested especially in your in this sort of idea of critical periods, and I thought was hoping you'd be a person who could explain that to us. Could you tell us, for someone that knows nothing about it, what what is a a critical period in in development or in brain development?
Dr. Dolen:Yeah. So just a formal definition, you know, it's a period of time when the brain is much more sensitive to its environment and able to learn from its environment in a in a heightened way. So a critical period for language, you know, mostly people are thinking about speech. So your ability to produce the sounds that are sort of the phonemes for the language that you are speaking is considered a hard critical period. Whereas the ability to learn a new language is more like a sensitive period because you can learn a new language as an adult.
Dr. Dolen:It's just much harder. You're much less fluid. You always have an accent. And so some people make that distinction between sensitive and critical periods. The first description of a critical period was actually imprinting behavior in greylade geese, and it was Conrad Lorenz who described it back in 1935, actually.
Dr. Dolen:So the concept has really been around for almost a hundred years. And since his first description of imprinting behavior in geese, you know, we've discovered critical periods in a bunch of different species in mice, in in rats, in cats, in ferrets, in humans, in songbirds. And we've discovered all kinds of different critical periods that regulate things like the formation of the visual system and the somatosensory system, the motor system. And my lab has really focused on a critical period for social behavior, which we discovered.
Kurt:Yeah. And what is the critical period for social learning that you discovered?
Dr. Dolen:Yeah. So the way we measure it, we're measuring it in mice, and we're using an assay called the conditioned place preference assay, which allows us to test the ability to learn an association between a cue and a context. And so in this case, we're using bedding because mice are, you know, olfactory specialists and it allows them to recognize the cues and distinguish them, and we're comparing the condition of isolation condition or social condition. And what we found is is that in juvenile animals, so the equivalent of around puberty in humans, the mice are able to learn this association between vetting and social really, really well. But as they get older, that ability to learn the association goes away.
Dr. Dolen:And so the way that I sort of relate it to people who are focused on humans is is that this is probably the type of social reward learning is the type of learning that teenagers are very good at. So they're they're very sensitive to peer pressure because they're they're wide open in terms of learning from their social environment. And they're paying a lot of attention to exactly, you know, what color jeans the popular girls are wearing or, you know, what are the rules of hierarchy? Who's the cool kid in school? Who's the prom queen?
Dr. Dolen:Who's the you know, all of these things. But by the time we get to adulthood, you know, those things are less important to us. We get more comfortable in who we are as we are, and we wear mom jeans because they're comfortable, not you know, we're not we're not so worried about impressing in that way.
Kurt:I think social phenomenon are always a little more complex, aren't they? I mean, maybe that's why people hadn't found or thought to look for. I don't know if they were looking or not for critical periods in this area before you discovered it. But maybe an example from a sort of maybe classic sensory issue. I think you had once described, like, in vision development of how it works exactly.
Kurt:You know? How how does time affect the way that something develops?
Dr. Dolen:Yeah. So the vast, vast majority of what we know about critical periods and their mechanisms come from studies of the visual system. So the first description of this critical period was around the ability of the visual cortex to change its response properties following a deprivation. So if you monocularly deprive an eye for about two to three days, typically, the way the experiments are done, then the circuits will become rearranged in the visual cortex. And now the the neurons that were responding to the eye that was closed, their response properties go down and the eye that stayed open, those response properties go up.
Dr. Dolen:So that change is called ocular dominance plasticity. And just like, you know, other critical periods, the ability to induce ocular dominance plasticity by this manipulation is highest in juveniles. And by the time the animals reach adulthood, it goes away. And this has clinical consequences because, for example, if you are born with cataracts in both eyes, if you don't have them removed by the time you're about four or five years old, then you will always be blind even if you have the cataracts removed. Because that critical period for structuring the visual system, the ability to process that visual information, once it's closed, even if you, you know, remove the impediment to, you know, visual information coming into the brain, once that that rearrangement is locked in, it can't adjust to the now normalized world.
Kurt:So, you know, in essentially, in a way, the, you know, development in anticipates certain sorts of stimuli and experiences at different points in time. And if we don't if we don't get those, then actually the brain doesn't develop in the in the sort of optimal or expected anticipated way that evolution has crafted for us. Is that right?
Dr. Dolen:That that's right. That's a that's a great way of putting it. The other way of thinking about it is is that, you know, the reason that we have critical periods is because there aren't enough genes in the genome to encode every single behavior. Instead, what gets encoded in the genome is the ability to learn from your environment. And this ability to learn, it has a progression.
Dr. Dolen:Right? So you can't learn everything all at once. Instead, you have to first, you have to learn to walk and then or prowl and then walk and then run. Right? And so those windows of time seem to be developmentally constrained to the appropriate window for that learning progression.
Dr. Dolen:But it also means that it enables humans and other animals who have these critical periods a huge amount of behavioral flexibility that wouldn't be available if they were trying to use genes to encode these behaviors. So instead of having 7,000 possible languages, we would all speak only one. Right? And so this is an advantage, but also a constraint that is imposed by setting the the brain up like this.
Kurt:And I think it's quite interesting. I I think outside the world of of, you know, perhaps professionals researching this or or or maybe those, you know, associated at the edges of it for clinical reasons, for example, Maybe people don't fully appreciate the the impact of those those developmental markers and that and how permanent they can be on all kinds of systems in the in the in the body and the brain. Right?
Dr. Dolen:Yeah. Absolutely. And I I think that, you know, I've given examples of things that are easy to relate to clinically. But I would also say that, like, your personality develops during this point. You know, I think the critical period.
Dr. Dolen:There are critical periods for motor learning. So the way you walk, the way you hold your body, the way that you, you know, react to certain stimuli, fearful or loving. You know, all of these things, once your critical periods have closed, they get sort of locked in. William James has a a famous quote that I'm paraphrasing. It says something like, if people could understand how quickly they would become a mere bundle of walking habits, they would pay more attention to their behaviors during the the plastic state.
Dr. Dolen:You know, I think he intuitively understood that plasticity relates and the change in plasticity across development, the change in the ability to induce plasticity, which we now call metaplasticity, that he intuited as, you know, being so important for the development of the brain and our and our habits and and learning and the circuits that encode, you know, vision, encode behavior.
Kurt:Are there ever ways that the brain itself reunlocks a critical period state?
Dr. Dolen:Yeah. So we think that, you know, habits get a really bad rap, but they are actually very adaptive. They allow us to navigate our world efficiently and productively and without having to, you know, exert a huge amount of emotional energy that we can, you know, therefore devote to other things. But they are really most useful so long as your environment is really, really stable. But when there are radical shifts in the environment, then those learned habits of behavior are not necessarily adaptive anymore.
Dr. Dolen:So we think that this ability to reopen critical periods is something that's built in whenever there's a radical shift in the environment. And I think that we have evidence not from, you know, a little bit from our lab, but mostly from from the literature that, you know, the old way of being able to reopen critical periods was through deprivation experiments. So if you, you know, visually deprive a mouse or even a human for, you know, two weeks, then you can reopen that critical period. And we think that religious practices like mystical traditions have been using this insight into deprivation, being able to induce open states of critical periods, you know, for centuries to be able to, you know, have epiphanies. We think, you know, this is what people are doing when they go and live in a cave for a month or they go on a silent retreat or they join a monastery and and, you know, deprive themselves of their normal daily activities and social interactions.
Dr. Dolen:They are essentially radically altering their environment. And that is causing the brain to say, wait a minute, something is off. All the the sort of statistics of our inputs aren't coming in the same way. Reset, reset, reset. You know, the analogy I give is something like, you know, if you're on a Zoom call and the screen starts to flicker, maybe you don't do anything with a few flickers.
Dr. Dolen:But if it freezes and it freezes for a couple of seconds, then you hit the reset button. You know, in terms of evolutionary selection pressures that would enable this, I think, you know, humans live a long time. And during the course of their life, things change. So, you know, hierarchical relationships, you know, are one thing when you're a juvenile, another thing when you are a young adult. And then at some point, you know, the elders start dying and your parents die, And now suddenly you are required to take that position in the hierarchy that, you know, used to be your elders, and now you're the elder.
Dr. Dolen:And so being able to adjust to those radical shifts and to now take on the behaviors of somebody who's at a different position in the hierarchy, I think that's enabled by this flexibility that happens when we have major life events.
Kurt:That's really interesting. It actually gives me goosebumps. I hadn't even considered most of those examples in that way, and I didn't know that about deprivation. That's kind of amazing, actually. It it happens after a stroke too, doesn't it?
Kurt:It's the things like that.
Dr. Dolen:Yeah. Yeah. So right after a stroke, for about two months after you've had the stroke, that window of the critical period reopens. And in some sense, the stroke is like an extreme deprivation experiment. Right?
Dr. Dolen:Like, you're used to having inputs coming in. Let's say you had a stroke that affected your arm, and now those arm movement inputs are not coming in. And so that tells the brain something's off, reset, and and we think, you know, nearby brain regions become plastic again, and it enables them to learn how to do the functions that used to belong to the jaw but now are are sort of repurposed for our movements.
Kurt:And it's it's a sometimes it's felt to me as a therapist almost a little unfair much happens in the very earliest period of life, right? Because it's a, I mean, although it's a very flexible system, I mean, as my mentors of developmental psychology used to say, right? Like, actually a lot can go wrong and people are still basically okay. But when things do happen, they they can sometimes have a a much much longer lasting impact, can't they?
Dr. Dolen:That's right. That's right. And I think that, you know, the the frustration that you're pointing to is one that, you know, not just therapists, but psychiatrists, neurologists, you know, have shared. And this is why, you know, in the in the field of neuroscience, there are, you know, three Nobel Prizes given for critical periods, 7,000 papers written about the mechanisms underlying critical periods because people who share your frustration have been hoping that we might someday discover a master key for unlocking critical period that would allow us to go back and and tinker with the things that didn't quite get learned in the optimal way.
Kurt:Well, I know that's just right where your research is. And being able to to open these periods and and to get into this plastic state, this very special kind of plastic state at will would be of obvious enormous benefit to medicine, for example, and maybe to humanity more broadly, but certainly to medicine, right?
Dr. Dolen:Right, right.
Kurt:Did you ever imagine that there would be like a medicine or a drug that might be able to help with reopening critical periods? It sounds like it's a relatively extreme states that have allowed for this in in other other arenas.
Dr. Dolen:Yeah. So the existing sort of deprivation based critical period reopening methods, you know, are not terribly therapeutically useful. I mean, nobody wants to cure their stroke by having another stroke. Right? So just not a useful way of doing it.
Dr. Dolen:And so, you know, people have been looking for these master keys. And honestly, when I was a graduate student, I poo pooed the idea. I I was very skeptical that we would ever get to a master key because based on what we knew about the mechanisms relating to inhibitory excitatory balance, extracellular matrix remodeling, metaplasticity. I thought anything that could do this, any any drug or manipulation that could be a master key for unlocking critical periods would dramatically interfere with the ability of the brain to, you know, not have seizures or it would, you know, cause amnesia or it would cause, you know, structural instability to the brain. And so I I was very, very skeptical of the idea that we might ever find a master key.
Kurt:Yeah. And a a master key, again, just being something that could could open open critical periods kind of at at will and presumably without the risk that they don't close again or that they have some problem like you described. Is
Dr. Dolen:that That's And
Kurt:so it turns out you ended up discovering that it's just such a master key also, That's right. Please tell me about that. I'd love to hear.
Dr. Dolen:Yeah. So we you know, the way we kind of came on the fact that psychedelics turn out to be this master key that we've been looking for is a little bit serendipitous. First, you know, my lab was studying social behaviors. That's really the main focus of the lab is social behaviors. And we knew that there was one specific type of psychedelic that was in the category called an empathogenic psychedelic, and this was MDMA.
Dr. Dolen:So MDMA is is known by its other names as ecstasy. It's an empathogen, so it induces a lot of sort of pro social behaviors in humans. And actually, we also showed it in octopuses and, you know, rodents. So it's a very prosocial psychedelic, and people who are using MDMA will report, you know, interest in being part of, you know, 30 person cuddle puddles at at
Kurt:You'll connect with others. You'll feel good
Dr. Dolen:about being around being others. You wanna touch people. You wanna understand their emotions. You're you're very sensitive to what they're feeling. And so we thought, well, if we're gonna reopen this critical period, you know, MDMA, because it has this prosocial property, might be just the one.
Dr. Dolen:And so we gave MDMA to our mice in adulthood when the critical period was already closed. And then we measured two days later. So we weren't looking we weren't after the sort of acute subjective effects of MDMA. We wanted to know what happened 48 later after the MDMA had had worn off. What did that do to the social reward learning?
Dr. Dolen:And what we discovered is is that it brought social reward learning back. And so suddenly, these adults were able to learn from their social environment in the same way that juveniles do. And when we ended that paper, so that was a paper that we published in 2019 in nature. We kinda finished that paper by saying, okay. We figured out why MDMA is so therapeutically useful for PTSD, and and it's basically enabling this social interaction that allows for the therapeutic alliance between the person who's being treated and and the therapist.
Dr. Dolen:We knew already that there was a little bit of a problem with that interpretation, which was the fact that when we gave MDMA in a social context, we were able to reopen this social critical period. But if we gave MDMA in an isolation context, then suddenly we weren't able to reopen this critical period. So what it suggested, that result was, first of all, it was satisfying because it provided an explanation for why the therapeutic context matters so much. You know, I always joke that you can't take MDMA and go to a rave and expect to cure your PTSD. You really have to pair it with the therapeutic context.
Dr. Dolen:So, like, if you take MDMA in a social context, you're much more likely to be social. But, you know, if you take it by yourself and sit on a couch, then you just wanna melt into the couch.
Kurt:So is the idea to is it has to be paired with the right kind of environment?
Dr. Dolen:Right. And, you know, recreational psychedelics users have known about this forever. They call it the set and setting, referring to the mindset and the situational setting. You know, as a neuroscientist, I call that context. But what it suggested is is that, you know, it wasn't necessarily about the prosocial properties of MDMA that there was something else going on.
Dr. Dolen:And so to test that idea, we compared this critical period reopening with a bunch of other drugs that were similar to MDMA. So first, we looked at cocaine, which is also a psychostimulant. And cocaine did not reopen this critical period, which was really, really important to us because that suggested that this is really a critical period, that this is really reopening, and that it's not just about having a nice party and reminding the animals how much they like being with their peers. Right? It's not about that.
Dr. Dolen:It's something else. So then we looked at other psychedelics. So we looked at ketamine. We looked at psilocybin, which is magic mushrooms. We looked at LSD.
Dr. Dolen:We looked at ibogaine, which is a sort of unique psychedelic that comes from Africa. And we discovered that every single one of the psychedelics, whether they had any of those acute prosocial effects or not, reopened this critical period. So the take home message is nobody's doing a 30 person cuddle puddle on LSD, and yet it was able to reopen this social critical period. And we've, you know, subsequently discovered that, you know, the context dependence also applies for ketamine. There's another group that has recently just shown, it's a paper up on bioRxiv, that psilocybin's effects are also if you pair them with isolation, they they fail to reopen the critical period.
Kurt:And there's a there's a an association, isn't there, between the effect of the experience and the link to the effect of the critical period reopening?
Dr. Dolen:Yeah. Yeah. So that was another, like, very cool sort of surprise to us. You know, I think my intuition going into those experiments that it would be the intensity of the trip that determined which whether or not the critical period was open and how long it was open. But instead, it turned out that there was it was the duration.
Dr. Dolen:So if you have a a psychedelic that causes a very short trip, so imagine ketamine, it's thirty minutes to two hours max duration of the trip. And there, the critical period only stays open for about forty eight hours. By four days, it's closed again. And on the other extreme, we have Ibogaine, which the trip lasts, you know, thirty six to seventy two hours. And now that drug is able to keep the critical period open for at least four weeks, but probably longer.
Dr. Dolen:And so that relationship between the open state of the critical period and the duration of the acute subjective effects, I think really convinced me that there's a mechanistic relationship between the trip and the and the opening of the critical period. And it also suggests that, you know, what it feels like to be in that open state of the critical period is just what it feels like to be in the altered state of consciousness induced by psychedelics. This finding actually has a lot of, you know, implications for how we implement psychedelics in a clinical setting. So the first is is that, you know, most of the clinical trials to date have really been focused on supporting the patients. You know, during the trip, people are focused on, you know, making sure that the patients feel safe, that they, you know, have the therapeutic guidance to get them to explore their trauma and that they feel supported and able to do that.
Dr. Dolen:And then afterwards, you know, there's there's some amount of emphasis on integration and and, you know, keeping a journal and exploring your new insights. But, you know, the the emphasis was really on the day of the trip has been traditionally. But I think that, you know, our studies showing that, for example, MDMA keeps that critical period open for about two weeks after the trip really suggests that unless we are, you know, engaging with the patients during that time and really getting them to integrate and create new habits of behavior around their insights from the day of the trip, it's a missed therapeutic opportunity unless we're really focusing on that. At the same time, on the on the sort of flip side of that, it also is a caution because, you know, I think that if you take people and you return them to this vulnerable juvenile state and then you, you know, kinda put them back into their busy lives, or at worse, you expose them to, you know, somebody who's gonna be a bad influence on them or who's their traumatizer, then you could make things worse. And so I think that we really do need to be more careful about the way we treat people after the trip is over, sort of in the same way as we, you know, we would never, after somebody had a heart attack, you know, send them home and tell them that they can go ahead and climb Mount Everest tomorrow.
Dr. Dolen:We're very careful and, you know, ask that they recognize that the heart is in this very vulnerable state and that it's, you know, susceptible to tearing in this recovery period and that they really need to be, you know, resting and and not producing not allowing themselves to get stressed out too much while they are while the heart muscles are being reconfigured and reconstituted.
Kurt:I myself am in the still fairly early days of recovery from a spine surgery a little more than a month ago. So they say, you know, that three months, you've got to watch out. You know, a lot has happened. So I know exactly what you mean. And so the cautionary note is probably useful.
Kurt:I mean, people could get overly excited about this and think, oh my god, I want redo too. You know, hard reboot. I'm having a hard time. But it might not have that expected outcome, you know, especially in a sort of, you know, uncontrolled environment or without certain precautions and safety nets.
Dr. Dolen:Yeah. So I would say that, you know, just like I mean, we have a tendency to wanna fix things quickly and be done with it, and especially if you are in pain, psychological pain is no different. You know, you want that pain to go away as quickly as possible. But learning doesn't happen overnight even for children in that natural open state of the critical period. And we need to be aware of the fact that, you know, time matters.
Dr. Dolen:And that if we don't give people enough time to integrate their insights into their lives, then, you know, the durability of the effects that we're most excited about. Right? So, I mean, you know, it's an opportunity to give people three medications and then have durable effects that last a year or longer. Right? As opposed to the current standard of care, which is that you have to take pills for possibly the rest of your life.
Dr. Dolen:But I really think that the durability comes from what it is that you learn during that the trip itself and in the weeks after the the trip is over and you're still in that open state of the critical period.
Kurt:Many psychiatric problems, just for example, are fairly long term problems. I mean, you know, that can be treated. I mean, I'm I'm always sort of boosting the effectiveness of the things that we have. I I wanna keep doing that. But we're also treating here a lot of folks that have not necessarily benefited from the things that help a lot of people.
Kurt:So there's a lot of people who are still suffering with things, post traumatic stress disorder, things that happen in early childhood, especially tend to be longer term things. So this is a, I would imagine for you an an exciting area of possibility in in this in this arena. I sort of wonder what what are you most excited about in the future directions of research in this critical period area?
Dr. Dolen:Yeah. So, I mean, when I first started working on this, there was a little bit of skepticism in the field because it was like, you know, people are saying psychedelics for everything. Right? Like, what does PTSD have to do with addiction? What does addiction have to do with depression?
Dr. Dolen:What does what does all of that have to do with you know, how is it that one class of drugs, which seems to be working through different receptors, how are they all doing the same thing? And I think that there was some skepticism that this was just, you know, placebo effects or wishful thinking on the part of the psychedelic community that it was gonna be so useful. And, really, I think that the critical period explanation does a good job of accounting for this diversity of diseases because if you think about it, every single one of them is a disorder that, you know, has a a learning component to it. Right? We've learned some set of behaviors that was adaptive at the time of, say, if it was PTSD, you know, was adaptive from during the the moment to to survive the injury, but over time are less and less adaptive.
Dr. Dolen:And so to be able to unlearn that is, you know, the psychedelic assisted psychotherapy, you know, the critical period explanation really, I think, does a good job of that. What it also suggests is this that there are a lot of other critical periods that are not kind of under the umbrella of psychiatry. So neurological diseases, there are plenty of neurological diseases that have learned components. And so what we are most excited about and what we're focused on next is motor learning following stroke. And so we have a clinical trial that is getting started soon, hopefully, that is gonna be looking at people who had a stroke over a year ago and their critical period is already closed.
Dr. Dolen:They're no longer getting benefit from physical therapy or occupational therapy. And so we wanna go back for those patients, give them psychedelics, and this time, instead of pairing it with psychotherapy, we'll pair it with occupational therapy and sort of somatic techniques for preparation and see if we can get them to that pairing to produce, you know, rehabilitative benefits in terms of their motor learning.
Kurt:That's so interesting. Mean, because the critical period reopening you've been talking about most has been this social reward learning critical period reopening. But that would be a different critical period entirely. Right? So there's some hope that maybe these these this category of medicines broadly considered might open other critical periods also?
Dr. Dolen:Yeah. So, I mean, we have my lab, you know, we're really focused on social behavior. But I will say that since our 2019 paper describing this critical period idea first, you know, there have been three other papers published showing that different psychedelics can reopen the ocular dominance critical period. I know two others that are, you know, in progress that are looking at, you know, the somatosensory critical period and and another one looking at the visual critical period. We have partnered with Steve Zeiler, who's a neurologist who's really, you know, pioneered, you know, developing a mouse model of motor learning after stroke.
Dr. Dolen:And so we're we're examining whether or not we can reopen those critical periods.
Kurt:I I'm gonna tell you, that's one of the most exciting things I think I've ever heard about in in in medicine and development. I mean, am I am I am I getting it wrong? Should I be as excited as I feel for the state of the research?
Dr. Dolen:Yeah. No. I I think it is exciting, and I and I'm trying to spread the excitement because I think that one of the things that happened last summer when the FDA failed to approve the drug application from Lycos, the company that was developing MDMA assisted psychotherapy is is that, you know, the the people on the scientific advisory committee to the FDA took one look at this data and they were like, this is too good to be true. You're either you messed it up or you're cheating in some way. This can't be you can't have an effect that is double the size of standard of care that just doesn't happen in psychiatry.
Dr. Dolen:But see, for those of us who have been studying critical periods our whole lives and who, you know, have been predicting that anything that could reopen them should be able to boost, you know, these types of learning behaviors, doubling them. This was exactly the kind of result that we would expect. So I want to kind of impress upon people that this mechanism, if it ends up being the one that explains psychedelics effects, you know, is predicted to have these massive effects and should generalize across a lot of different types of behaviors, because and that's why neuroscientists have been obsessed with them for the last hundred years.
Kurt:And sometimes, you know, I know people are skeptical of things that seem too good to be true. But but also if you look at the history of, you know, discoveries in in and out of medicine, I mean, they sometimes move forward in these kinds of leaps, you know, many people involved. But all of a sudden, there's, you know, there's penicillin. All of a sudden, there's vaccines. All of a sudden, there's that.
Kurt:Right? I mean, almost living memory, we have these things. Right? I mean but so why not again? Right?
Kurt:Yeah.
Dr. Dolen:I'm I'm very excited about it. And I think that, you know, those people who have used a lot of psychedelics, you know, find that this explanation is very intuitive for the way that they have experienced it. But, you know, that is not enough for me because psychedelics in general have, you know, a noetic property and they are, you know, very suggestible. And so if people have heard about this and then they experience psychedelics, they may be more inclined to interpret their experience through this lens because just because of the what the drugs are doing. And so for me, the most gratifying part of it is getting this result in mice.
Dr. Dolen:The mice, they're sort of a natural double blind placebo control. Right? Like, they don't
Kurt:They know precious little about Timothy Leary or something. Right?
Dr. Dolen:Exactly. They know precious little
Kurt:about Timothy Leary.
Dr. Dolen:And so, you know, to be able to get this objective measure and now to have several labs finding exactly the same thing for different critical periods that their expertise on, you know, is very gratifying. But, you know, I think that if we if we manage to show improvement in stroke, then that will be, you know, a major leap forward because I think it will shift the conversation, which is right now very much focused on do we need therapy or do we not need therapy? And it's all about psychiatric illnesses. But if we can demonstrate it with stroke where, you know, in neurology, the notion of having therapy is already, you know, very well established. Nobody would tell a person who has a stroke, you know, sorry, we we cleared your blood clot, but therapy is too expensive.
Dr. Dolen:You go on home. That would just never happen in neurology. And so I think that if we can demonstrate this principle, this proof of concept in a disease a therapeutic setting that where therapy is already well established as as necessary and an important component of how you get recovery, then I think it will shift the conversation in a in a big way.
Kurt:Well, doctor Dolan, I've I've kept you from your research long enough and and should maybe feel guilty about Maybe the state of the field is an hour behind now. But I'm I'm grateful, and I think our listeners will be too. So thank you. Thank you so, so much.
Dr. Dolen:Thank you very much for having me. It's been a pleasure.
Mary:Wow. What a really interesting conversation. The idea that there could be these master keys that could unlock these critical periods that we once thought were closed forever could just have wide ranging impacts in so many different fields.
Kurt:I know. From from stroke to mental health to who knows what I mean, I I'm more excited about this kind of research than anything I've heard of in years. If if this pans out, this is gonna blow the lid off of a lot of science and could be really profoundly transformative. Really interesting kind of amazing stuff. I just sort of of want to abide in that wonder of this possibility of where where this very serious research might go.
Mary:Yeah. And she has a whole body of work, and her research is ongoing. So if you'd like to learn more about it, we've put a link, in the show notes to the Dolan Lab.
Kurt:Yeah. Lots of wonderful information there, and there's some other interviews and things like that that she's done. We can link to those. Some of them get into a lot more detail about the psychedelic angle of this and everything else. But I I certainly am gonna to keep these critical periods in mind, and maybe I can one day get some sort of treatment.
Kurt:It'll make it easier for me to learn Italian. Wouldn't that
Mary:be great? I
Kurt:can almost hear her saying, don't hold your breath. We're working on stroke.
Mary:Right. It's more serious issues.
Kurt:Unraveling is brought to you by Brattleboro Retreat. Our producers at Charts and Leisure are Andrew Adkin, Hans Beuteau, and Jason Oberholzer.
Mary:And you can find us on social media by searching Brattleboro Retreat. Brattleboro Retreat is committed to exploring diverse perspectives on mental health. While we invite hosts and guests to share their insights, the views expressed are their own and do not necessarily reflect the policies or positions of the hospital or its staff.