Gül Dölen on Rethinking Psychedelics

Gül Dölen

Of mind, it's not really a branch of philosophy or anything. It's just a thing that has drawn the attention of philosophers from a variety of different perspectives. Like you can imagine considering what is the mind from a metaphysical point of view. So what are the things that we count when we say this is what a mind is, this is what a mind is not, then there are other considerations like, well, how do we know mind? Can we know mind just through introspection or is there some empirical way or some way that we can compare different people's descriptions of those things to get at what is mind? And that would be sort of the more epistemological approach to mind. And I was interested in all of those things. There continues to be debate about that. And one of the interesting ideas that I came across was that there was this concept of theory of mind, which is not really a theory in the way that we have a theory of light or a theory of synaptogenesis Or any of the more commonplace theories. It's more like it's a point of view. The shorthand way of explaining what theory of mind is that I like to tell people is it's sort of what you're doing. It's the

Gül Dölen

Of mind, it's not really a branch of philosophy or anything. It's just a thing that has drawn the attention of philosophers from a variety of different perspectives. Like you can imagine considering what is the mind from a metaphysical point of view. So what are the things that we count when we say this is what a mind is, this is what a mind is not, then there are other considerations like, well, how do we know mind? Can we know mind just through introspection or is there some empirical way or some way that we can compare different people's descriptions of those things to get at what is mind? And that would be sort of the more epistemological approach to mind. And I was interested in all of those things. There continues to be debate about that. And one of the interesting ideas that I came across was that there was this concept of theory of mind, which is not really a theory in the way that we have a theory of light or a theory of synaptogenesis Or any of the more commonplace theories. It's more like it's a point of view. The shorthand way of explaining what theory of mind is that I like to tell people is it's sort of what you're doing. It's the neurobiological process that is going on when you're playing poker. It's anticipating what somebody else might be thinking and trying to see the world from their point of view. So in some sense, it's a theory about what somebody else might be thinking.

Gül Dölen

I like this idea because it was a testable hypothesis. And one of the things that I found sort of frustrating about being a philosopher is that the philosophers were always asking the coolest questions, the biggest questions, but just Felt like, you know, they were just going around in circles and never really coming up with an answer that I found to be deeply satisfying. And on the other hand, you know, scientists, neuroscientists, you know, maybe they weren't getting to ask all the really big questions, but man, they were coming up with some concrete Answers that felt tangible and like we were getting somewhere. And so I like this idea that we could test the requirement of theory of mind for consciousness by looking at diseases where that function is impaired and learn something about the relationship Between consciousness and genes that encode different proteins that are required for that theory of mind.

Tim Ferriss

I have many, many follow-up questions. Theory of mind does not seem to be, based on the reading that I've done, entirely human-specific. And is it true that you have observed this in, for instance, and your tapping on the shoulder made me think of it, hunting behavior in octopuses?

Gül Dölen

And on the other hand, you know, scientists, neuroscientists, you know, maybe they weren't getting to ask all the really big questions, but man, they were coming up with some concrete Answers that felt tangible and like we were getting somewhere. And so I like this idea that we could test the requirement of theory of mind for consciousness by looking at diseases where that function is impaired and learn something about the relationship Between consciousness and genes that encode different proteins that are required for that theory of mind.

Tim Ferriss

I have many, many follow-up questions. Theory of mind does not seem to be, based on the reading that I've done, entirely human-specific. And is it true that you have observed this in, for instance, and your tapping on the shoulder made me think of it, hunting behavior in octopuses?

Gül Dölen

Those were actually not my experiments. Those were experiments done by really eminent octopus researcher Roy Caldwell, and he showed me the videos of them. And as soon as I saw the videos of the octopuses hunting, it occurred to me that that is exactly a theory of mind-like behavior in an octopus.

Gül Dölen

They will kill each other. And there are, you know, differences in the amount of aggressiveness that we observe in octopuses. You know, some are so aggressive that we've never even seen the males of the species because when they mate, they like leave their hectocotylus arm, which is their reproductive arm In the mantle of the female and eject it and escape so that they don't get eaten. So we've only ever found their hectocotylus arm. That's how aggressive that species is. Okay. So other species of octopus aren't quite so aggressive, but they're still asocial. And it was interesting because the species of octopus that does that hunting behavior is the only known social species of octopus. It seems like an interesting opportunity to test these ideas about what are the selection pressures that make theory of mind develop across evolution and what are the species specific Advantages to having a theory of mind. But it's interesting also because even though the larger Pacific striped octopus, which is the octopus that does that hunting behavior, is social, it's not using this behavior in A social context. It's using it in a hunting context, which suggests that, you know, maybe

Gül Dölen

So that was really exciting. Something like 26 other labs followed up on that work. And several big pharmaceutical companies said, okay, this is it. This is the mechanism-based therapy that we've been looking for, and ran several very large-scale human clinical trials for that metabotropic glutamate receptor modulator that We thought would correct the imbalance in Fragile X. And when they did those studies, everybody was hugely disappointed because we were expecting, you know, the drugs to work and to cure the disease. And we really got very little evidence to support that view. And I think at the time, all the people who were doing human research and clinical trials were just willing to throw their hands up and say, well, see, we told you a mouse is not a human. And that's why the trials didn't work because all of the human trials were based on mouse studies and this was just where we went wrong. But a few of us kind of took a more circumspect view and said well yeah okay mice aren't humans but there were a lot of other differences between the human trials and the mouse trials and

Gül Dölen

Believe, I mean, it's been a long time since I was in medical school, but last time I was, I looked into that, I believe it was still the case that FMR1 was rare enough that it wasn't worth It to do the screening test to try and find it because, you know, you have to balance doing a screening test against the possibility that the test itself is going to cause problems with The pregnancy. And so there is a sort of a judgment call there. And unless you had a family history of Fragile X, I think that it's still the case that people don't actually test for it beforehand. It's not like Down syndrome also, where there's any strong indication that in Down syndrome, you know, there seems to be, there is a correlation between the age of the mother and the Likelihood of getting Down syndrome. For schizophrenia, there seems to be a correlation between the age of the father and getting schizophrenia. But for autism, as far as I know, there is no age-dependent correlation with your likelihood of getting it. And all of the causes of autism are each individually so rare that there's no screening test that is generally applicable that would be worth doing.

Tim Ferriss

Let's just revisit, as promised, the reopening of the critical period.

Gül Dölen

The idea of critical periods first came in 1935 by Conrad Lorenz, who is a ethologist who was studying imprinting behavior in snow geese. So this is the

Gül Dölen

Of critical periods first came in 1935 by Conrad Lorenz, who is a ethologist who was studying imprinting behavior in snow geese. So this is the behavior that shortly after hatching, the animals will form a long lasting attachment typically to their mother. But if the mother isn't around and instead it's, you know, sort of a motorized airplane or the scientist in that case, Conrad Lorenz himself, then they'll form that attachment to that Other moving object in their vicinity. And, you know, there are all these funny pictures online of Conrad Lorenz being followed around by little snow geese, right? Because they formed this attachment.

Tim Ferriss

Wait, what are snow geese?

Gül Dölen

They're just a type of geese.

Tim Ferriss

Okay, there we go. Just wanted to figure out. Sounds like a little Scandinavian dwarf or something. No, no, no, they're just like type of geese. Type of geese, birds, okay?

Gül Dölen

So they're just followed around by these birds. They're really cute pictures. And this imprinting behavior, though, if you wait, so if you wait until 48 hours after hatching, then they don't form this behavior, right? So this attachment is only possible within the first 48 hours of hatching. And Conrad Lorenz called that period of time when the animals are extremely sensitive to their environment and can form these long-lasting

Gül Dölen

Of critical periods first came in 1935 by Conrad Lorenz, who is a ethologist who was studying imprinting behavior in snow geese. So this is the behavior that shortly after hatching, the animals will form a long lasting attachment typically to their mother. But if the mother isn't around and instead it's, you know, sort of a motorized airplane or the scientist in that case, Conrad Lorenz himself, then they'll form that attachment to that Other moving object in their vicinity. And, you know, there are all these funny pictures online of Conrad Lorenz being followed around by little snow geese, right? Because they formed this attachment.

Tim Ferriss

Wait, what are snow geese?

Gül Dölen

They're just a type of geese.

Tim Ferriss

Okay, there we go. Just wanted to figure out. Sounds like a little Scandinavian dwarf or something. No, no, no, they're just like type of geese. Type of geese, birds, okay?

Gül Dölen

So they're just followed around by these birds. They're really cute pictures. And this imprinting behavior, though, if you wait, so if you wait until 48 hours after hatching, then they don't form this behavior, right? So this attachment is only possible within the first 48 hours of hatching. And Conrad Lorenz called that period of time when the animals are extremely sensitive to their environment and can form these long-lasting memories, he called that window of time The critical period. And critical periods since then have been described for so many different things. So probably the one that most people will be familiar with is the critical period for language learning.

Gül Dölen

Trying to figure out how you fit in. And sometimes you want to just get on with it. And if the environment that you're in is stable, then you don't need to necessarily be adapting or adjusting your model of the world every single move that you make. And so that's why we think that critical periods close. But then another question is, why does the brain have a sort of ready-made mechanism that psychedelics can tap into for reopening critical periods, right? Like, why can we reopen them so easily if the brain wasn't already built to do this? And this is, you know, really me speculating, but I suspect it's because when we have these habits, they're adaptive so long as the environment is stable. But then there's a radical shift in the environment. Then you can imagine that it would be adaptive to be able to reopen critical periods and relearn from your environment. So going back to the language example, you know, as long as everybody around you speaks English, it's probably not all that adaptive to be learning Spanish. But if you move to Spain or you move to Central America, then suddenly nobody's speaking English and you want to be able to learn the language that everybody's speaking around

Gül Dölen

There's evidence for this, that this deprivation induced, you know, can also reopen our social critical period. So here's another rule that kind of applies across critical periods is that deprivation is a technique. And so this might be the explanation, for example, for why it's easier to learn Spanish if you go to Guatemala than if you go to Costa Rica, because in Costa Rica, everybody speaks Spanish, But everybody also speaks English, right? So it's very hard. You're not deprived of English. You're just exposed to Spanish. Whereas in Guatemala, almost nobody speaks English. And so you're deprived and you get the language. So that's one idea that we have. We haven't proven it. But the other part of that is that it's interesting to note that historically, religious practices across many, many different cultures have used deprivation techniques to get to That mystical state that people talk about. Zen Buddhists call it beginner's mind. If you were looking for a neurobiological description of beginner's mind, reopening critical periods would be it.

Tim Ferriss

How do strokes fit into this?

Gül Dölen

For a long time now, clinically, we have known that right after you have a stroke, you have this very short window of time, really, really closed by three months, but really you want to Get in there within six weeks to two months or so, where physical therapy is going to have its maximal effect or benefit for helping you to recover the motor function that you lost because Of the stroke. Okay. And that window of time, you know, we don't exactly know why it closes, but it seems to be that it's not that the damaged part of the brain suddenly re-sprouts neurons. It's that the brain regions immediately adjacent to the damaged part of the brain become flexible again and able to perform or control the motor functions that were lost by the brain Region immediately next to it. And that window closes, just like all other critical periods close. And so far, the best way that we have for reopening that critical period is to give another stroke. But nobody wants to cure stroke by giving another stroke. That's just not a clinically useful way. Hard to sell. Hard to sell that.

Tim Ferriss

Yeah, definitely hard to sell.

Gül Dölen

Even harder. And so we like the idea that maybe we could branch out into other critical periods like this one to see whether or not psychedelics can reopen that critical period for stroke. And we have a collaboration with Steve Zeiler,

Gül Dölen

Is sort of venturing off into politics, which is a hobby, not my area of expertise. But I would certainly say that if we look at the percentage of taxpayer money, well, first of all, in the 50s and 60s, we collected a lot more taxes. Today, we give away more in tax breaks than the entire discretionary budget, back to big corporations as incentives and tax breaks. But really, most of those corporations, the thing that they are making and selling right now, especially in the tech industry, are possible because the taxpayers in the 50s and 60s Made those investments in the science and technology areas to develop all of the computing and software building science and research that that stuff was built upon. Facebook and all of these tech ventures that we and Google and cell phones and computers, they didn't just happen to arise out of America for no reason.

Gül Dölen

Did we wander into this political sphere? Probably the ones that I have gifted the most is a book called Invisible Women by Carolyn Criado Perez. You know, I really love it because I think it's a book of feminism that is accessible and I think resonates with people whether or not you're a man or a woman. It's just data. It's like, all right, well, you know, here's how much it costs to keep ignoring women. And if you fix it, your city can save a million dollars a year. It's all about the structural stuff. It's not about your feelings about whether women deserve to be in the kitchen or not. It's not about that. It's just here's how ignoring data about women's body sizes, women's travel patterns, ends up costing society at large. And I think it's an excellent way of kind of getting that. And then the other book that I love the most, it's a very grandiose title. It's called The Dawn of Everything, A New History of Humanity by David Graber. I actually love everything that that guy wrote. I started with this book called Bullshit Jobs, which, you know, I was dealing with like the bureaucracy of academia and feeling very frustrated. And I read that book and it was very cathartic. And then I just kind of went down the rabbit hole and have enjoyed all the other books. But The Dawn of Everything, it's a big book and it's pretty thick, but the last chapter has some really cool stuff about psychedelic uses in other cultures. And then the third one that I really love is The Immortality Key by Brian Marescu. I love that book so much. I designed my entire Halloween decoration this year all around that book.