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Dr. Gül Dölen

lines on the record: 110
first: 2023-04-19
most recent: 2023-04-19
sittings or episodes: 1
sources: podcast

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“God, I can't think of it. I think this has been one of the most fun meandering conversations. I feel like we covered everything. I look forward to doing it again sometime because I really do think that in the next few years, we're going to have some pretty ground shifting stories coming out. And I would love to come back and share them with you.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Well, I loved that book also because my family's from Turkey and one of the places that he mentioned is Ephesus, which is, you know, an hour and a half drive away from my mom's house. And, you know, I'm definitely, next time I go to Turkey, I'm visiting Ephesus to try and figure out those hecate carvings and maybe take a little soil sample.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Entire Halloween decoration this year, all around that book. And, you know, I send pictures of it to Brian and he was like, oh my God, you nailed it. I got to up my Halloween game. So yeah, those are the three books that I would recommend.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“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 Graeber. I actually love everything that that guy wrote. I started with this book called Bullshit Jobs, which, you know, I was dealing with 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. Like I designed my”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“How 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.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“And all of these tech ventures that we and Google and cell phones and computers, they didn't just tap into arise out of America for no reason. They came because the United States for years understood that this was an investment for the Weiwei future. And so I think changing our tax structure to sort of reinvest in the future of science, it's either going to happen or it's not. It's going to move to other countries and places like China that are investing in science and technology and this sort of non-goal-directed just throw money at it and eventually something cool will pop out attitude. I mean, that's just my two cents. So I hope I don't insult like half your audience, but that's what I think.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“I'm just wondering This 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.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Curiosity. And I would say every person who becomes a scientist at one point or another had that as their motivation and the strain of the funding crisis is essentially what has forced people to get more and more and more conservative. So I don't think I'm unique for wanting to just see what happens when you give octopuses MDMA. In fact, I think the reason that everybody responded to that paper so well worldwide is because every single one of us has that curiosity, has that, I wonder what would happen, you know. And it resonated with people. And I just think mostly gets beaten out of us because of funding constraints.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Required for that test is made by those bacteria that live in those weird thermal vents. And so I think this non-goal-directed curiosity-based science, it doesn't show any usefulness for 40, 50 years. So it takes that long for something meaningful to come out of that kind of discovery-based, curiosity-based science. And I think that the way that funding constraints and the way that tech and even private foundations are very goal-oriented, right? It's like, well, how can we sell this? How can we market this? And, you know, the private foundations have names like Cure Autism Now. They're very goal-directed. And I think that that sort of kills the motivation or the impetus to just do the weird stuff that's just for fun.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Scientists are seeing less and less of that kind of crazy stuff is really the funding. I mean, the funding, just to give a sense of this, I think this is a really missed point, especially with tech. So in the 50s and 60s, the NSF, the National Science Foundation, and the NIH were sort of funding all kinds of crazy stuff that they just never thought would ever be useful or have a goal. They were just funding it. And so when Thomas Brock was like, there are these weird bacteria that live in these thermal vents in Yellowstone National Park. Give me some money to go figure out how they can survive those temperatures. NSF was like, yeah, sure, here you go. If they hadn't given him that money, the PCR test that we all learned about during the pandemic would not be possible because that enzyme that is...”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“First of all, I don't want to oversell how big of a risk it was for me to do that experiment. We were already working on MDMA. We already had reasonable response from nature about the MDMA critical period experiment. The octopus thing was really kind of like, well, we had the MDMA around and I've always been curious and I just wanted to see what would happen. And then a collaborator was like, well, we have seven octopuses that we can lend you for a week. And I was like, come on down. He flew down. He slept on my couch. We stayed up until like two o'clock in the morning every night, like just doing it mad scientists because we had to send the octopuses back by the end of the week. And, you know, it's just like this mad scientist fun time, right? And so how do I preserve that? Well, I guess part of, I think, the reason that we as”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Just out of curiosity. I just want to know what happens. And then it worked and it revived my sense of play and joy and feeling like you can do those crazy experiments that everybody thinks are crazy and have fun with it.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“I've always wanted to study evolution. I've always wanted to do something to do with marine neuroscience. I have this opportunity to look at what happens to this behavior in an octopus. I'm just going to go for it and it'll be fun. And even if it doesn't work, even if it is not useful for my career in any way at all. Like, I mean, I would go to these meetings, faculty meetings and meetings with my department chair and I'd tell them we were planning to do this octopus stuff and he'd be like, cool, what are you doing? We hired you to cure autism. What is this octopus stuff? Like what? And I just be like, look, you got to back off. This is what I want to do. This is what's going to make me feel like science is fun. Like I'm doing it, not in a goal-directed way, in a kind of playful.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“And I was like, I can't do this. I thought I was becoming a scientist because I was going to get to pursue these big questions and be creative and steer my own ship. That's what I had worked so hard for as a graduate student, as a postdoc, and as a medical student, that was the dream that I was sold. And I was pretty devastated by how many rejections I got. And so In that moment, when I was like, all right, I'm going to try a couple more times, but if I don't get it, that's it. I'm out as soon as I, you know, my department was very supportive. They're like, you'll get there, you'll get there, you'll get there. We'll cover you. Don't worry. Don't fire anybody. You're good. But still, it's a blow to your ego if you can't convince your peers at the NIH to give you that money. And so going out on my own terms, I was just like, look.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“With the different whatever, very conservative kind of rinse and repeat type of experiments. And over my scientific career, I have seen that situation essentially reversed. So people over the age of 65 are getting most of the NIH grants. Junior people are really struggling. And there have been some attempts to correct that. They just haven't worked and it's just incredibly difficult to get funding. And then if you add on top of that, the funding has gotten so conservative that basically the way that I write NIH grants right now is like.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“You start your own lab, you get a bunch of money and that startup package is great to kind of get you started, hire some people, buy some equipment, get your lab established without having to worry too much about the funding. But when I started my lab, I got a nice startup package. I immediately got a couple of private foundation grants, which were very helpful to help me establish the lab. you know, you really can't in academia survive unless you can also get funding from the NIH. And these big NIH grants have, in my career, in my lifetime, have gotten harder and harder to get. And it used to be that people who were young and had a lot of creative ideas had much higher success rates than people who were older and kind of just redoing the same experiments.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Going to be the key. And so I think if we can get people on psychedelics plus put them in this motor play context, then we can maximally recapitulate the conditions that we learn how to do motor function when we're developing as children.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Is much more sort of goal undirected kind of play wandering, don't care if I fall down a million times. I mean, there's this great idea that children walk when they're learning how to walk will walk the equivalent of seven football fields in an hour. Now, the only time I've ever seen an adult do that is on MDMA. So they will just dance and they don't care if they look like fools. They don't care if they're not good dancers. It's not goal directed. They're just enjoying the play of doing the motion. And so what I like about Steve and John's approach to motor rehabilitation sort of without psychedelics is that their virtual reality system that they've built is very much capitalizing on this non-goal-directed play-like behavior. And I think that's.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“No, no, no. It would be concurrent, but I would say it's not going to be practice-based. So one of the things that I would want to emphasize is part of the reason that I paired up with Steve Zeiler and John Krakower at Hopkins is that their approach for treating stroke during the normal period is already open, right, is that they've said, well, you know, most of the physical therapy that patients receive is very goal-directed. I need to learn how to zip my pants with the other hand. I need to learn how to comb my hair with the other hand. And so it's very much practical solving the problem another way. Whereas the way that we learn those motor patterns when we're children”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“To reopen them for as long as you possibly can to get the maximal effect. And, you know, we'll have to work out how to do them back to back to back. But that's sort of how I'm thinking about it there. The second sort of thing I want to unpack about your question is that you mentioned for the stroke that you were imagining that we would be giving the psychedelic and the person would be practicing a bunch of things in a very specific directed way. And actually that's not how I'm imagining that this will work.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Antidepressives or SSRIs. What we really need to be thinking of these as is more like surgery. If you have a heart attack, you go and you have open heart surgery. It lasts for eight hours. You have maybe two or three weeks afterwards where you are required to be on bed rest and take things easy. But then you're cured, right? And so who wouldn't rather be cured of a heart attack than have to be on a medicine for the rest of their lives? I think most people see that as the major promise of psychedelics. So in terms of the therapeutic approach, I think the way I'm framing this stroke trial is really like I'm not worried about the fact that they're going to have to do a psychedelic and potentially the maximum benefit is going to be from these long acting psychedelics because I think that these motor critical periods are pretty strong closes and so you want”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Four weeks or four months, we're not sure. But it's not the case, for example, and then, you know, psilocybin, MDMA, and LST are in the middle there between those two extremes. But it's not the case that if you double the dose of LSD, then you can get LSD to open the critical period longer, for example. And so that dosing business, I think, is going to be a little bit of a heartbreak for all of the pharmaceutical companies out there that are essentially trying to engineer out the psychedelic effects by shortening the duration of the psychedelic effects to get less side effects in a shorter journey that will be easier to manage in a clinical setting. And again, what can you do? Nature is nature. But I do think that it changes the model of how we approach these. Rather than thinking of these as next generation anxiolytics or next generation.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“There are two questions in there. Let me just pull them apart for a second. So, the dose issue are studies that we've done so far suggest that there's a pretty narrow dose response for reopening critical periods that matches what we see in humans for the acute subjective effects. But we don't see any evidence that increasing the dose necessarily increases the opening of the critical period or how long the duration of the critical period over.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Interdirected trip with a lot of psychotherapy makes a lot of sense for PTSD and addiction and depression, it's probably the wrong context for stroke, whereas doing a lot of physical therapy and movement and playing virtual reality motion games might be the right context for giving the psychedelic for stroke for allergy maybe the right context is snuggling up to that horse or that dog or that cat that you're allergic to, right? And so I think the future, the therapeutic potential for this, the opportunity is huge, but the devil is going to be in the details in terms of identifying the right context and figuring out how to get activation of the right neural circuit that's relevant for the sort of brain transformation that you want to see happen.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“That context is really what matters. So, for example, the clinical trials where context is sort of secondary, where the psychotherapy is essentially there in case somebody has a bad trip, but it's not really front and center to the intervention. Then I think those trials for psilocybin, for example, aren't working as well as the trials where, you know, it's really seen as an adjunct to the primary therapy, which is the psychotherapy. Now, if we're right in the critical period reopening explanation is this shift in the framework for how we understand these therapeutic effects, then in 10 years from now, the way that psychedelics are going to be used is going to be trying to identify that right context for the right disease. So while an”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“If this ends up being true, then it's going to be a pretty big paradigm shift for neuropsychiatric treatments. Because let me just back up and say I have to give a little bit of credit to maps here because Maps did a lot of really hard work to convince the FDA that the way to design clinical trials around psychedelics was to abandon the sort of one variable at a time test model and say, look, we really need to pair these drugs with psychotherapy because the drugs are not doing the magic by themselves. It's really this combination that's working. And so that I think was a big shift in the way that the FDA wants us to test drugs in clinical trials. I think that we're beginning to see more and more evidence.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Of the ritual might be actually really important to how these drugs are working therapeutically. And unless we understand it from our context, we won't be able to readily adapt.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“But include things like face painting and social touch and the whole community is involved for this three-day long trip that a person goes from one house to another, right? And it turns out that a lot of those elements that we might not necessarily recognize as important that we might dismiss as ritual in a mouse, we can recapitulate, right? We know that MDMA's ability to reopen the social critical period is social context dependent, right? If we give it in isolation, then it doesn't reopen. So it turns out that there are all of these elements that go beyond just the molecule, and we can't just import, take the thing that we decide is the most important element, the molecule, and import it into our medicinal practices and our cultural history without understanding it because many of those elements”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Let me just riff on that for a second because, you know, I think that that's a really important point about the context. So the context of disease is also different in this culture versus other cultures and how a disease is defined as different across cultures and how you might approach a disease is defined differently across cultures. And so a good example is the way that IBAN is used traditionally. You know, in these cultures that using IBAN for traditional healing practices, it's not just that the person taking it has a disease and they're being treated. It's sort of a mix between they have a disease, but they also have something to share with the rest of their community. And the whole IBAN experience is encapsulated in a bunch of things that we as Western doctors might dismiss as just ritual.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“But I think that if this ends up being true that this mechanistic explanation can really open up whole new avenues that people hadn't been thinking of before, then I think that that's a testament to the importance of always keep an open mind, always look for more answers, more questions, and keep searching.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“I'm just curious what MDMA will do in an octopus. It was totally curiosity based science. And to see it evolve into something that can potentially help so many people is as a scientist just super gratifying. It's pretty rare. Nobody really gets to have those kinds of woohoo success stories. And so that's very gratifying to me on a personal level, but also I think that for all of the psychedelics enthusiasts out there, it's a lesson in how important it is to never stop learning, never stop questioning. You know, I think there was an intuition a few years ago that, well, Indigenous people have been using psychedelics forever. We don't really need to understand their mechanisms. We don't really need to dig into how it is these things work because we know they're going to work because they've got this long history behind them.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Yeah, definitely hard to tell. Even harder, you know, 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, who's a neurologist at Johns Hopkins, who has developed a rodent model for that critical period of motor recovery following stroke. And he also has a stroke clinic at Hopkins. And so we're working closely with them to see whether or not this idea really can help these patients, which basically it's a 400,000 patients a year in the United States who have debilitating, lasting impairments because of stroke. So it's a huge number of people. And it's super exciting because, you know, here's something that we started out with.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“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.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“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. 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 resprouts 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 regent immediately.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Access to the truth. But now I really know. And so for a scientist, that's pretty dangerous. For a scientist, you always want to be able to have a little bit of skepticism about what it is that you have discovered. You always want to keep your ideas as sort of provisional until, you know, the next test comes along, until, you know, it should always be a working model, never a this is the Ten Commandments of Neuroscience. That's not the way that we do science. And so the Noetic property, I think, does mean that that experiment where you take a bunch of bacteria and give yourself ulcers is a little bit harder to justify in this nursing psychedelics. So that's how I.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Scientists were just like rapt attention, right? Because this is it, like this is what we all dream of as neuroscientists is to have some manipulation that we can give in this case a drug that is dramatically altering the way that the brain is functioning and interpreting the world around it. And here is this chemist sort of”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“I got to tell you a funny story when he came to visit MIT when I was a graduate student. It was sort of the opening party for the new building. And I won't name any names, but there were, you know, everybody had invited a bunch of Nobel Prize winners who had discovered every cool thing in biology. And they all got up there and not necessarily knew anything about neuroscience. They were all sort of older. And they kind of gave a little biography and then sat back down. And then Sasha got up on stage and he was just basically the same age as everybody else, the only person without a Nobel Prize on that stage. And yet, he was so alert and so adept. And he was like, oh, and then we added this methyl group over here and this happened and, you know, the behavioral response. And then we did this and we got ego this. And we put that on there. And all of the nurse.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Historically, it has been thought to be a signal to the cell that says pull in the receptors. I really loved the idea that even though not all psychedelics bind to the serotonin 2A, most of them You could imagine a scenario where they were triggering beta arrest and signaling over G protein coupled signaling and that if you knocked out the beta arrestin protein that you could block the ability of psychedelics to reopen critical periods. And while that was true for some of the psychedelics, it turned out not to be the universal mechanism that spans across all of the psychedelics. So that was a little bit of a bummer, I have to say, because I thought, all right, we'll solve it. It'll be done. And, you know, I can rest easy, but it didn't work out that simple. Mother Nature always likes to trip us up like that.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“gonna be a long night exactly And that's the half off. So only half of it comes off in four and a half hours, right? And so this was like a really important insight into why it is the LSD's effects last so long. But when it sits in that receptor for too long, instead of signaling through the normal G-protein coupled signaling pathway, what happens is it starts sending signal to the cell, no, instead of G protein, you need to hit a different biochemical pathway. We need to trigger beta arrestin. And beta arrestin is just another biochemical pathway that gets triggered by that receptor being activated too long. And what is thought that beta arrestin does is rather than do the second messenger signaling, it says to the cell, pull that receptor out, we're about to get toxic damage from too much receptor activation. So beta arrest and signaling.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Now that's just how they normally signal. But when a drug like LSD binds to the serotonin 2A receptor, Brian Roth's group has shown that when it sits in its receptor, it has an unusually long off rate. So normally when transmitters get in their receptor, they jump in and they jump right back out. So they pop in, pop out really, really fast, okay, less than a second time scale. LSD, when it sits in the serotonin 2A receptor binding pocket, a little lid kind of comes down and locks it into place. And when that lid locks the LSD into place, it's off-rate goes to four and a half hours, which is like insane.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“So basically, most of the psychedelic drugs, except for ketamine and PCP, are acting at what are called G-protein-coupled receptors. Okay, so when I was talking about NMDA receptors versus mgluR receptors, the difference is M gluRs or G-protein coupled receptors and NMDA receptors are ion channels, so they're inotropic receptors, right? So metabotropic inotropic, it has to do with how they're coupled to internal signaling. So all of the G protein coupled receptors, including almost all of the serotonin receptors, they work by when the drug binds to their binding pocket, they induce a series of biochemical events, either excitatory or inhibitory biochemical changes downstream that are sort of the second messengers, if you will, of the receptor binding.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Because it's not very pleasurable. You know, nobody wants to take it. I don't want to overstep the capa opioid stuff. The reason that we got interested in it is because IBAN also has high affinity for Cappa opioid receptors, but it also acts as serotonin transporters. So I really don't know what the answer is there. I thought the beta arrestin story was going to nicely sew everything up and it just didn't.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“I mean, people have been excited about cappa opioids because it sort of thought to be that's going to be the one that's going to make you not be addicted to it. And it's not very pleasurable. But because it's...”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“And we don't have strong evidence to support this, but this is our working model involves calling in all of the receptors, internalizing them, cleaning up the”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“We're coming upon is that it's not the receptor, it's not even one step downstream of that. People have been excited about the possibility that changes in biochemical signaling at the level of beta arrestin might be the next step after the receptor that might be common. We don't see that to be the case in our studies. And what it seems to be is downstream of that even more, which is regulation of the extracellular matrix, which we think is sort of the final common pathway that happens. And the working model that we have is that psychedelics bind to their receptor. And when they sit in that receptor for too long, it signals to the cell, oh no, oh no, excited toxicity is coming. Hit the reset button. And what that does through a variety of different mechanisms is we think.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Context dependent long term therapeutic effects of psychedelics that we see in humans. And so I think it's up for debate whether or not the serotonin 2A receptor is required. But what we do know is that psychedelics that have primary binding at NMDA receptors, serotonin transporters, serotonin 2A receptors, kappa opioid receptors, ones that span the diversity of receptors all show some therapeutic effect. And so our lab has really been focused in trying to understand, well, what's the commonality across all of those receptors? And so to kind of in a long-winded way, get back to your original question, what we wanted to know is what's downstream of those receptors that's common to all of those psychedelics? We don't have the complete answer yet, but the answer that”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“And I begain and ketamine from the definition of classical psychedelics. But I personally feel that this is putting the cart before the horse because we don't know that that is necessarily a good boundary for defining psychedelics. First of all, because we know that most of the psychedelics are very promiscuous in their binding. Second of all, we don't really understand whether or not the 2A receptor is required for the therapeutic properties, right? So there is some evidence that there are antidepressive properties that may or may not be blocked by serotonin receptor antagonists. There's two papers that have exactly opposite results about this right now. I am not entirely convinced that those antidepressive properties that they're measuring have anything to do with the durable.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“People are now trying to call the classical serotonin psychedelics like LSD, mescaline, psilocybin, DMT, and then also the weird ones like MDMA and IBAN. And most Snyder and Alexander Shulgin consider all of those drugs to be psychedelics. More recently, there has been this push mostly led by the chemists to say, oh, no, no, no, no. If we look at the receptor binding properties of these drugs, the classical psychedelics, the hallucinogenic psychedelics, they're all serotonin 2A receptor binding. And even though they're promiscuous, even though they're binding to a bunch of different receptors, the psychedelic effects seem to be mediated by this receptor using pharmacology studies in humans. And they are really pushing hard to kind of exclude MDMA.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Let me back up for a second and just explain that there's sort of a debate going on in the field right now because there are, if you look back in the textbooks written in the 70s and 80s about psychedelics, textbooks written by people like Solomon Snyder who started my department at Johns Hopkins and discovered almost every neurotransmitter receptor you've ever heard of, including by the way the serotonin 2A receptor. Their definition of what a psychedelic is was very broad, right? So they basically said, you know, it's anything that causes this altered state of consciousness, altered perception of time, space, body, self. These were all sort of things that psychedelics do, and they included psychedelics ranging from ketamine, PCP, what”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT
“Bring him up Yeah, and I mean, I love the idea because I actually kind of wanted to be a veterinarian, but I'm allergic to horses, dogs, and cats. So I would love to take psychedelics and cure myself of those allergies. And while I love this idea, I don't believe it enough yet to, you know, take a bunch of psychedelics and go snuggle up to a horse because I think, you know, we could be looking at anaphylactic shock in that situation. So I don't believe it yet, but I like the idea as something that we could test.”
2023-04-19 · The Tim Ferriss Show · #667: Dr. Gül Dölen on Rethinking Psychedelics, New Applications (Autism, Stroke, and Allergies), The Neurobiology of Beginner’s Mind, Octopuses on MDMA, and The Master Key of Metaplasticity · IDENTIFIED FROM THE TRANSCRIPT