The Tim Ferriss Show - #507: Dr. Adam Gazzaley, UCSF — Brain Optimization and The Future of Psychedelic Medicine

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Starting point is 00:04:16 Optimal minimum. At this altitude, I can run flat out for a half mile before my hands start shaking. Can I answer a personal question? Now would have seemed an appropriate time. What if I did the opposite? I'm a cybernetic organism, living tissue over metal endoskeleton. The Tim Ferriss Show. Hello boys and girls, ladies and germs. This is Tim Ferriss and welcome to another episode of The Tim Ferriss Show, where it is my job to interview world-class performers from all

Starting point is 00:04:49 different disciplines, all different areas, to tease out habits, frameworks, lessons learned, tools that you can use, insights that you might apply to your own life, questions that might enable you in some fashion. My guest today is close friend, Adam Ghazali, MD, PhD. You can find him on Twitter at AdamGhaz, G-A-Z-Z. Adam is the David Dolby Distinguished Professor of Neurology, Physiology, and Psychiatry at the University of California, San Francisco, and the founder and executive director of Neuroscape, a translational neuroscience center engaged in technology development and scientific research of novel brain assessments and optimization tools. Dr. Ghazali is co-founder and chief science advisor of Akili Interactive,

Starting point is 00:05:34 Sensync, and Jazz Venture Partners. He has been a scientific advisor for more than a dozen technology companies, including Apple, GE, Nielsen, and Deloitte. Ghazali has filed multiple patents. Let's try that again. Let's try that. I might keep that one in. Ghazali. Also, I just never refer you to as Ghazali. Anyway, Ghazali. I like it though. Ghazali has filed multiple patents, notably his invention of the first video game cleared by the FDA, authored more than 150 scientific articles, and delivered over 675 invited presentations around the world. God, that makes me exhausted just reading it. He wrote and hosted the nationally televised PBS special, The Distracted Mind with Dr. Adam Ghazali and co-authored The Distracted Mind,

Starting point is 00:06:16 subtitled Ancient Brains in a High-Tech World, winner of the 2017 PROSE Award. Dr. Ghazali has received many awards and honors, including the 2015 Science Educator Award and the 2020 Global Gaming Citizen Honor. You can find him online in several places, ghazali.com, as well as neuroscape.ucsf.edu, and on social, on Facebook, Instagram, Twitter, Adam Gaz. And you can also find him on LinkedIn. He is easy to find. There aren't many Adam Gazalis running around. Adam, welcome back to the show. Thanks so much, Tim. Excited to be here with you. I am excited also because you have what appears to be a professional sports center broadcasting headset. Those who are not watching video can't see it, but I am very reassured that if this neuroscience thing doesn't work out for you, you have a compelling plan B. It was quite a way to overdo the Zoom world that we live in now with this headset, but at least for this podcast, I will be well heard. So thank you.

Starting point is 00:07:17 And thanks to Matt Mullenweg also for his tech enabling. For people who did not join us in the first conversation we had on the podcast, I wanted to mention a few highlights or just a few topics that we brought up. So the first conversation we had, I didn't realize until doing prep for this conversation, because there was a summary of our previous conversation, which said, Kevin and Daria Rose are moving to New York. And I thought to myself, good God, how long ago was that? And it was 2015. So in 2015, it's been a long time and your bio has developed quite a bit since. And the title of that was the Maverick of Brain Optimization. And I'll mention a few reasons for choosing that title. And that was my choice. I don't think you would choose that for yourself.

Starting point is 00:08:08 We discussed many things. And I want to paint a picture of some of the tools and types of development that you have explored in your time as a scientist. And one of those is NeuroRacer, which is a piece of software that was featured on the cover of Nature. The title, as I remember it, was Game Changer. And when you correct me if I'm wrong, I'll just try to summarize this really quickly. But the paper was able to show that a team of scientists could work with video game professionals to build something customized that targets processing the brain that's deficient in a certain population. I'm going to ask you to just give some numbers in a minute. But in this particular case,

Starting point is 00:08:47 it was older adults and their cognitive control abilities. So some might say age-related cognitive decline. And then once you've built the software, you can construct a carefully controlled study, placebo-controlled, with neural measurements to document the mechanisms of effect and show that you can create sustainable and meaningful changes in the brain using a video game. And just as a footnote, that cognitive abilities begin to decline around, or certain cognitive abilities around what, early to mid-20s? That's accurate. So what were some of the outcomes of the study or the paper that was featured on the cover of Nature? Yeah, that was really quite a game changer for me as well. Only time has told how far that technology and that research has gone, and we could dive into what it's become now.

Starting point is 00:09:40 It's fun to think back, you know, that paper was published in 2013, and it took five years of both tech development to build that video game with friends at LucasArts, as well as to do the multiple research studies that went into that paper in Nature. And why it was so exciting was that what we were able to show was that we can improve the ability of these healthy 60-plus-year-olds, not just to play the game, but their ability to sustain their attention in a very boring context, as well as their working memory, holding information in mind for short periods of time. of 20-year-olds. So it was really reversing a lot of the changes that occur with healthy aging. And we could see those changes occurring not just in terms of their performance, but neurally, because we recorded with high-density EEG how they responded to these challenges before and after a month of gameplay. We could then look over time, six months later,

Starting point is 00:10:42 and actually we have a paper that is just being accepted for publication now showing six years later that in these older adults, we see some benefits, not all the benefits retain over that period of time, which is really quite exciting. It opens up the possibility to really push what we can do to lead to these sustainable benefits. What was the age range of subjects, roughly, or the average? They were 60 and over. I think we had one that was a 90-year-old, but mostly 60 and 70-year-olds. And the game, the software, as an intervention, was able to restore or revert some of their cognitive function to the level of 20-somethings.

Starting point is 00:11:27 Is that accurate? Yep, that's accurate. And just to restate what you said, for people who might have missed it, and please again, correct me if I'm wrong, but the durability of effect, in other words, seeing the retention of a lot of these improvements six months later was not because they continued to play this game on a regular basis going forward. Correct. They did not play it at all, even though many of them wanted to after the one month of training. And so that's why when we brought them back just recently, this is not

Starting point is 00:12:01 published, it'll be out soon, six years later, their ability to play that game at a much higher level than they did before was retained without any boosters. And this is not a real-world design because as this becomes a true treatment intervention that we want in the real world, and we could talk about where it's gone, we would not think about that type of durability as the goal. It would be more reasonable to boost those effects over time with doses along the way. Just like if you were going to enhance your physical performance, your strength, your aerobic ability, you wouldn't think, oh, a month in the gym and then I'm good till six years later. So the fact that anything lasted is sort of mind-boggling to me as a neuroscientist, but it's more of a proof of concept that these circuits and

Starting point is 00:12:53 these abilities, when they change, can be enduring. But in the real-world implementation, it would make much more sense to, in a personalized way, boost these effects along the passage of time. For those not involved in scientific research, what would you compare being the cover of nature to? I mean, is it comparable to winning an Oscar for best director or best picture? I mean, that's how I've in some ways thought of it because I don't have perhaps other comparables, but I know you're very self-effacing and humble when we talk and also just in general, but it's a big deal. It is not a small accomplishment. I'm just wondering how you would describe that or compare that to give people an appreciation for what that represents? Yeah, it's sort of around as big a thing can happen as a scientist. And probably,

Starting point is 00:13:55 if it happens, it all will happen once in a lifetime. Having a paper in Nature Science, those are like the pinnacle journals in the world, those two, the Twin Towers. And having a paper in them is incredibly rare and exceptional. And then having a cover story is just a once in a lifetime. And my friend, Mickey Hart, who's a musician, he's the drummer from The Grateful Dead, he always jokes me, I think it's like a Grammy and it's like a mixed feeling about it because you get it and it changes your life. And it did. You're like, oh, that means that that was the pinnacle of my life. And everything after that is just not as good. It's not going to happen again. And I have tried again, and we've had some really great papers over the years, but in all likelihood, that's the only time that's going to happen in my life. Well, never say never. Never say never. That's true. I'm going to try. I'll keep trying now.

Starting point is 00:14:50 So a few other things I'd love to know. The next is that you, I think, are very ambitious and calculated at the same time. So on one hand, you might say that you not just enjoy, but look for risks that you can take, say related to the video game connection, because you don't want to be you personally. And then I think maybe by extension to your lab, this would also apply, but you don't want to be the scientist

Starting point is 00:15:20 who is simply building on whatever came before in an iterative incremental incremental approach? Is it fair to say that you are looking for groundbreaking discoveries or groundbreaking development of tools? Is that a fair statement? I've always been motivated. I mean, since I was a little kid, when I thought about science and thinking about the giants in history whose names you still remember millennia later. Those were my heroes, not the baseball players or musicians. It was always those scientists.

Starting point is 00:15:53 And looking at their accomplishments, what got me so excited about going into science in the first place. When you approach science in that way, you realize that wanting to do it is only a piece of the puzzle of getting there. And even having the ability and skills to do it is still only a piece. It's a convergence of those things and time. Frequently, other events that are outside of your control that all lead to a moment where you get to make a contribution at that level. And that was always my dream, but it doesn't mean it's going to happen. To sort of answer your question directly, in order to get there, I tended to think about the research that I wanted to do from that perspective. And not just because I wanted a big claim to fame, not that that's not, not a great goal, but my real goal is to make, make a meaningful difference in humanity, in the world and help people. And I felt that in order to do that, you really have to sort of step out of the box, so to speak, and not

Starting point is 00:16:58 be iterative and do the thing that takes a little bit more fearlessness and a little higher risk. And it's okay to fail. But if you don't try, then there's no chance that you're going to make a difference at that level. And so that's how I've always approached it along my career. And now that I've had some successes in it, you get even braver, I would say. And I want to give a few more examples of the types of tools and work that you do within your lab. I'll first just read a quote from our first conversation asking, it was in response to me asking what makes your lab unique. And please feel free to fact check

Starting point is 00:17:43 this, but I believe it's accurate. The question you ask yourself is, how can we use our expertise or methodology, our perspectives, to not just understand the brain, but to try to develop novel approaches to enhancing it, and then validating that our approaches are actually effective? That I believe was in the first episode. And in the process of following that question, you've, for instance, studied how electrical currents can enhance brain function in non-invasive approaches with things like TDCS. And this is, I suppose, as good a place as any to segue to a new addition to your bio, which refers to this FDA clearance of a video game. What does that refer to? My goals have always been to not just have a super long CV with lots of recognitions and awards,

Starting point is 00:18:37 which is often what scientists, even my great friends who I respect dearly are building. I wanted to do research that then leapt off the page and became tools that would enter people's lives and make a meaningful difference to them. And I quickly realized that I could not do that within the chambers of academia alone. I had to leave and not necessarily leave, but I had to cross over. I had to find a way to move technologies and invention and discovery from the lab into the real world. In order to do that, it involved working with industry in some way. You don't really produce scalable products in labs, in academic labs. It's just not structured for that. And so the NeuroRacer technology, the video game, and really the methodology behind it,

Starting point is 00:19:33 which was a patent that I filed at UCSF that is now issued. It took six years to issue that. With that technology, I co-founded a company called Akili Interactive with friends from the video game world, Matt Omernek, as well as Eddie Martucci, who was working with a group, Pure Tech Ventures, in Boston. the time that we formed the company, beyond a prototype and an academic exercise that leads to a paper, even a paper as good as a nature paper, that wasn't the goal. The goal was to turn it into a product that would be a medical device that can actually serve as a new form of medicine. Beyond the molecular medicine is what I now think of as an experiential medicine or digital medicine that could lead to improvements in attention in different clinical populations. And so over the last seven years plus, we've now, at Akili, we've built a better version of NeuroRacer. Better meaning that it has higher levels of art and music and story and interactivity

Starting point is 00:20:47 and feedback loops and usability, but preserves the same underlying architecture, the same mechanism that is defined in the patent that was in NeuroRacer is in this game called EndeavorRx. And over these many years, Akili has sponsored research at academic universities to validate this video game, this child of NeuroRacer, as a clinical tool, as a treatment in numerous populations. So studies in autism and depression, ADHD, multiple sclerosis have been published now, all converging on the same conclusion that this game can improve attention abilities in these different populations. So even if there's a different reason why an individual has an attention deficit because they have a sensory processing disorder as a subset of autism, or they have depression,

Starting point is 00:21:46 we see the same benefits, which is really exciting because you get that really broad effect. And so to go back to where you introduced this, a study was done out of Duke. I was not even an investigator on that study, which is, that's the dream, right? That you create the technology and then other colleagues and other independent investigators validate it. So this was a study out of Duke by a really great clinician scientist, Scott Collins. And it was a really unique study methodologically because it was a multi-site, double-blind, placebo-controlled trial with a video game in children with ADHD. So 350 kids, years, millions of dollars, a big, actually not the type of studies I like to do at all, but a big important study. It's called the phase three trial. So it's a pivotal trial. It's the type of study you do that you pre-submit

Starting point is 00:22:38 to the FDA, all your design elements, your outcome measures. It's like a baseball player, you know, sort of pointing into the distance saying, this next shot is going to be this home run and how that's so much more meaningful because you call it in advance. And that's what you do in these studies. You have to like pick your outcome measure and what you expect to see before you even do this study, because that's the most statistically rigorous way to show that this is a true effect. And that's what was done in this study. The hypothesis was that the sustained attention of these children, which is very impaired beforehand, they have ADHD. So sustained attention is vigilance in a really boring environment. It's designed to be boring, this test, that that would improve in response to this video game

Starting point is 00:23:23 compared to another group of children with ADHD that's playing a different video game. And so that study took years, and that hypothesis was confirmed that those children did improve. The other group, the other game didn't change at all, and so it was specific to this game Endeavor Rx. And with that finding, we, as Achille, presented to the FDA the results requesting approval for clearance of a medical device. It's either a drug or a device. One is de novo, meaning it's completely new. There's no predicate. It's essentially establishing a new category of treatment. And the other is the predicate, the 510k pathway, where it rests on a previous history. And so it's much faster to get approved through that pathway than the de novo, the new pathway. And so because there had been no video game and no treatment of this type ever cleared by the FDA, it was a de novo pathway, which made

Starting point is 00:24:32 it a lot longer and more rigorous of a review process. But we found out during COVID, just in the summer of 2020, that the game was cleared. So this was one of those small blessings, as my friend Michael Pollan said, a silver lining in the pandemic blanket. And so what we found was, as we went through this process, the FDA was willing to clear this as a treatment for inattention in 8 to 12-year-olds. That's what the study was done on with ADHD, which was just an amazing result after a decade of journey from NeuroRacer to this, because now what we wound up with was the first ever FDA-cleared digital treatment for children and the first digital treatment for ADHD and the first video game for any clinical condition.

Starting point is 00:25:20 So it was a long journey, and I want to give all the hundreds of people at Achilles and Neuroscape credit, as well as the independent investigators like Scott Collins for all the work and pushing it through. But now we have it's de novo, right? This is a, in a sense, in several senses, sort of establishing and validating a new category, right? I mean, that's a new category of treatment or intervention. One question that pops to mind is what the underlying mechanism is, or if you can explain why the game, Endeavor RX, seems to be effective in multiple populations. You named a few, depression, ADHD, autism, or certain types of autism. Multiple sclerosis, we've now found.

Starting point is 00:26:21 Multiple sclerosis. What is the, even though these conditions manifest and present in very different ways in a bunch of respects, what is the commonality or why is it effective? Why is the intervention effective across these different conditions? Yeah, it's a great question and a complicated, longer answer. It would probably be required to really break it down, but to just give, you know, at least a basic understanding of how that's possible, it really is through the window of cognitive neuroscience that that makes sense. If you look at the pathology of those conditions, it's more confusing and elusive of why they would be connected to have a common treatment

Starting point is 00:27:02 lead to benefits across them. But from a cognitive neuroscience perspective, which is my background over the last couple of decades, is that there are common underlying networks, neural networks in the brain, that subserve different abilities like attention, memory, decision-making, emotional regulation, on and on. And these networks could be damaged, influenced in all sorts of ways by many conditions due to different reasons. When it comes to our attention systems, the networks are so distributed that any insult to the brain, I would say, I'd be as bold to say that any real insult to the brain that leads to any cognitive deficit is going to have a component of attention deficit associated with it.

Starting point is 00:27:50 So if you look across all the neurological and psychiatric conditions that you could think of and put it into PubMed or Google Scholar with the word attention or distraction, you will find research showing that they have impairments in that. And that's just because the act of focusing our limited mental resources on something that is a goal of ours, which is the core of the type of attention we're talking about, sustaining selective focus on something that you choose to, top-down attention, that that process involves so many distributed brain areas that all these different sources of pathology lead to decrements in that ability. And so if you have an intervention like NeuroRacer and EndeavorRx, which challenges cognitive control at a very high level due to

Starting point is 00:28:42 closed-loop systems in a personalized way, like the ultimate trainer, constantly pushing and optimizing those abilities over weeks and even months sometimes. Then what you wind up with is a transfer of benefits to cognitive control challenges outside of the game that's independent of what the cause of those deficits were. I think that gives you a bit of an idea of how you can have a outcome that sort of crosses all these boundaries because the same networks are vulnerable in all these populations. So anything that can optimize them could lead to a benefit across them. Could you, for people who don't have any real perspective or context on UCSF, just describe UCSF? What is UCSF from the perspective of research or looking at it as an institution of science. What is the best way for people to think about

Starting point is 00:29:45 UCSF in the kind of ecosystem of research within the United States? It is a massive and humbling honor for me to be at UCSF myself. It was always a dream to come out here to California and work at this institution. A lot of people don't know UCSF, University of California, San Francisco. They might familiar names like Stanford, Harvard, MIT, largely because UCSF is only a medical and health center. We do not have an undergraduate campus. There's no just engineering department. Everything's bio, bioengineering, biochemistry, but it is one of the world's premier medical centers pretty much across every domain, especially in neuroscience, neurology, neurosurgery, psychiatry.

Starting point is 00:30:30 In those areas, in the brain areas, is UCSF's forte from many perspectives. And so it's always ranked as one of the top in the country and even at world measures when it's put to the test or different evaluations. And from my perspective of being a faculty member here for now 15 years, it's amazing. I mean, every other faculty member I would meet without knowing anything about them, I'm excited because there's something about them, why they're here at UCSF, that I just want to find out. And then, of course, from just a clinical perspective, like I would send anyone in my

Starting point is 00:31:03 family without hesitation. And yeah, it's just a wonderful, wonderful place to be a scientist. Just a quick thanks to one of our sponsors, and we'll be right back to the show. This episode is brought to you by Wealthfront. Did you know if you missed 10 of the best performing days after the 2008 crisis, you would have missed out on 50%, 5-0% of your returns. Don't miss out on the best days in the market. Stay invested in a long-term automated investment portfolio. Wealthfront pioneered the automated investing movement, sometimes referred to as robo-advising, and they currently oversee $20 billion of assets for their clients. Wealthfront

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Starting point is 00:32:13 account. They've really thought of a ton. They've checked a lot of boxes. Smart investing should not feel like a rollercoaster ride. Let the professionals do the work for you. Go to wealthfront.com slash Tim and open a Wealthfront investment account today, and you'll get your first $5,000 managed for free for life. That's wealthfront.com slash Tim. Wealthfront will automate your investments for the long term, and you can get started today at wealthfront.com slash Tim. I want to come back to the risk-taking, the concept of risk-taking for a second, and then we're going to talk about new chapters. We're going to talk about new areas. When I hear you talk about risk-taking and translating science into the world for impact,

Starting point is 00:33:02 it strikes me that on one level, you could look at some of the projects and things that you've done as risky in the sense that there's a possibility that they do not work and they're in many senses not incremental. You're not just adding an extra 5% on top of something that's already been demonstrated. At the same time, when I look at how well you've been able to recruit and how well you've been able to retain and how effectively you've been able to build and grow, this is a leading question, obviously, but would you agree that that ambition and the willingness to take things that one might consider risky on as projects is a critical ingredient in all of those things. I feel like to foster an environment where you can do all of those things,

Starting point is 00:33:53 where people will put in lots of hours and effort over a long, sustained period of time, like you mentioned, the years required for some of these breakthroughs, that that risk taking seems to be a critical ingredient, almost a prerequisite for that type of enthusiasm. That's at least my perception. But what are your thoughts? I agree with you. I think that's part of it. And when you create an entity, I think at the time that we last talked, it was my lab. It was Ghazali Lab. That's a pretty classic way of how labs are named after the PI. And since then, my lab has just exploded. And now it's not a lab anymore.

Starting point is 00:34:32 It's a center where there are multiple faculty. We have now seven faculty members. And I think the reason that that has happened is because of the type of risk-taking that I am willing to do, but also how we build, we, my whole team, builds a system of security in that risk-taking. Because it is a long time to go without a publication when you start one of these type of studies. I mean, it could be five years before you're even writing up a paper. And therefore, in order to jump off of that, you know, that bridge with your bungee on,

Starting point is 00:35:09 you have to have security in the bridge and in the bungee and in the instructors and the person that ties it on. And so it's a whole community effort to create the platform that allows risk to be taken in an appropriate way, right? Because if we were just reckless, who would join that and where would be the means to assemble an all-star team of staff and postdocs and students and faculty? They wouldn't gather. So I agree with you. I think that

Starting point is 00:35:42 that's all tied together of what it means to take a risk, to do something bold, but to do it in a way that's thoughtful and not reckless. And you used a term, just for people who may not recognize it, you said PI. That is not Magnum PI. Oh, sorry. Investigative Principal Investigator, if I'm getting it right. Sorry, so much jargon. Correct. Yeah, which refers to the lead researcher for a grant project.

Starting point is 00:36:09 How many folks do you have within the Neuroscape endeavor on that team? Neuroscape's a center. We just call it Neuroscape. And we have over 40 people on payroll now. And we also work with a lot of contractors and volunteers, and that number's well over 60. So it's a big group. And it's been quite a change for me as a PI, as a principal investigator, to become a director and to really help other scientists upcoming in their careers to spread their wings and to really take those calculated risks as well under this community of Neuroscape that we created.

Starting point is 00:36:48 You know, it's so wild, Adam. I just have to say, to think back to when we first started spending time together, looking at the evolution of the bio, reading it for the podcast, just the change since 2015 and seeing how much you have done since I took also my first step into the world of scientific research from the standpoint of funding with that very first check, whatever it was. Yeah, which I think was like 2012. Yeah, 2012, something along those lines for Gazali Lab. And it just makes me so happy to see how incredibly well you've been able to execute.

Starting point is 00:37:32 And not just execute as an independent soul scientist, but also assemble and retain top talent. It's very impressive to me. I just wanted to say that. Thanks. It's very impressive to me. I just wanted to say that. Thanks. It's also fun. It's always a real pleasure to talk with you, Tim, because we have so much history. Going back over a decade when we met, and I can't help but, like you're doing, is thinking back in those early days when you even joined us for a bit on some brain stimulation work to help us out in the lab and just how much has changed since then. It's fun to think back, not just what the list of papers are, but the actual journey and

Starting point is 00:38:12 what was involved in assembling the people and the uncertainty, even when we were talking over the years where it was not FDA cleared and it was uncertain if it would be because of all the challenges of going through a de novo pathway. So it is really gratifying to talk to you now after all these years and see where we've come. Yeah. I remember trialing very, very early versions of NeuroRacer with the cap on and also having, right exactly, the EG cap on and also having you help, I think it was my middle finger to jump, kind of dance around with the TMS applied to, was it M3? Yeah, yeah, yeah, motor cortex, yeah. Exactly. So it's been a hell of a journey, man. Yeah.

Starting point is 00:39:03 And it's not over. No, not at all. It's been a hell of a journey, man. And it's not over. No, not at all. I think it's fair to say you're in a position where you get to pick your targets. I mean, you have done exceptionally well. You've established incredible defensible credibility. You've had Game Changer, NeuroRacer on the cover of nature. You have this well-developed center, right? You have Neuroscape, which is not just up and running, but really humming, right? I mean, it is a formidable organization. You can really choose what you want to do and what you want to focus on. So I suppose this is as good a place as any. Could you please tell us about what the new undertakings are and I suppose the announcement? And we could start with the announcement and then

Starting point is 00:39:57 go into backstory just to hear how you got to this point. Or we could start with the backstory and then get to the announcement. I agree. Let's not bury the lead. We'll tell what's going on and then we'll break it down so that everyone could enter this conversation with that full knowledge. So over the next couple weeks, we're in the process of announcing, we're going through this right now, announcing a new division within Neuroscape that will focus on psychedelic research. So Neuroscape's psychedelic research division is being launched and we're very, very excited about it. We're also really excited that this division will have at its helm Robin Card Harris, who will be joining us as faculty at Neuroscape and will be the

Starting point is 00:40:47 director of the center. And that's incredibly exciting for me. Robin is a leader in the field of psychedelics, has become a very good and trusted friend, and I'm honored and humbled in many ways that he's willing to travel across the world over from the UK to join us to be the founding director of this division within Neuroscape. He'll also be coming with an incredible position, the Ralph Metzner Distinguished Professor of Neurology and Psychiatry. Incredibly excited for him to start his new journey within UCSF and within Neuroscape and to advance psychedelic research

Starting point is 00:41:26 to the next level. So that's the lead. We can talk about how all that happened. Yeah, let's talk about it. I also want to just note, because I find it so incredibly inspiring, that things happened very quickly. And not just quickly for within the scientific sphere, but quickly, period. If I remember, you look back at email threads and just looking at the sort of time period that transpired after you first connected with Robin and as everything unfolded, it was very fast.

Starting point is 00:42:02 And I think that's extremely inspiring and demonstrates what's possible within universities and teams that are able to embrace this as a direction. I just think it's incredibly impressive. Yeah, I'm really, really pleased with how rapidly we've been able to do this, especially during COVID. Nothing really seems to happen fast during these days. And it's a reflection of the people involved, the university spend time talking about that, those things allowed it to move so rapidly in that it just felt right and made sense from pretty much every perspective. Not that there wasn't a lot of logistics and politics and negotiations, but the core of why this was the right thing to launch this division within Neuroscape, to have Robin lead it, it just makes sense. And so with that force, all the other pieces were able to fall into place.

Starting point is 00:43:16 Yeah, well, with a big enough why, right? A lot of the other things fall in line. How did this come to be? Please share whatever you think might be helpful to paint a picture of how and why this came together. Yeah, it's great. I've never really told this story yet, and I was sort of saving it to tell with you because you were one of the inspirations in it, not just a friend of mine. But if I go back to 2019, which is, you know, not all that long ago, even into the sort of mid and late 2018, conversations that I had with friends, including you, about psychedelics as a medical tool really ignited my imagination. This was sort of converging with my own goals of thinking about what I was going to do next

Starting point is 00:44:03 as a scientist, as an innovator, to not be iterative. I've had the success with video games as a therapeutic tool, and this was before the FDA clearance, and there's so much more work to do in that domain, and we will do it, and it's a lifetime of effort to continue to advance that. But I was thinking about the next decade moving from 2019 into 2020 and beyond. And I was looking for something that was not brand new. I don't want to plant a new tree. I'll have more branches, but I'm not going to start over from the beginning. It had to be within the scope of where I felt my expertise lied, what I enjoyed doing, the methodology and the skills of my team at Neuroscape. So it had a fit in that picture. And I started exploring what that would be.

Starting point is 00:44:51 And when I heard my friends talking about psychedelics, I live in San Francisco, and certainly a lot of people here have for decades- Easy to find a conversation. Easy to find a conversation, exactly. And I never really thought about it from a scientific perspective as a neuroscientist in that way, which is sort of says something. You know, I did an MD and a PhD. I did a full neurology residency. I'm at UCSF. How come never during all of that training was psychedelics ever presented in an academic manner as being a potential tool. Not once, never, which is fascinating. And we know a lot of the political and social reasons why that's true, but it's still mind-blowing when you think about that,

Starting point is 00:45:38 given all of the neuro education that I've had over the last 30 years. But once I started thinking about it, I decided to dive in a little deeper. And the first thing was reading Michael Pollan's book, How to Change Your Mind. I know you're also friends with Michael, and I did not know him at the time. We're close by geographically. He's at UC Berkeley and a professor there. I'm at UCSF, like right across the bay, half an hour away, but we never met each other. And I read that book and something did change in my mind. And it's really clear what it was. It wasn't just that I saw the clinical potential of these compounds. That was obvious. And I knew that already. It was that

Starting point is 00:46:17 what happened when I read that book was that I realized that these are not really molecular treatments. They're not drugs in that classic sense of introduce a molecule, lead to an effect, right? Just pop this in your mouth and your cold is gone, sort of like how in the infectious disease world, how we think about drugs. I realized that these were experiential treatments and experiential medicines in much a similar way to what I was doing with video games, that it is the molecule that initiates a series of events in your brain that leads to an experience, and that experience leads to an outcome. And that outcome could be good or it could be bad, but it doesn't just depend on the drug. It depends on the intersection of that

Starting point is 00:47:02 and you and the context around you and the experience itself. And that was like an epiphany for me. Maybe it was obvious to others, but I just never really thought about it from the same perspective that I was engaging in our work at Neuroscape, which is creating these experiences as medicine. And once I realized that, I was like, oh, this is it. This is the area that I can contribute to in a unique way because of the work that I've done at Neuroscape. And also, I believe, elevate this field because it is the area of psychedelic research and psychedelic science that I think is most efficient and missing in order for it to translate most effectively.

Starting point is 00:47:46 And so with that, I began a journey throughout 2019 and 20 to meet the people that were shaping this field, to read the literature and really understand the potential here. So everyone from Michael Pollan himself to Robin Carr at Harris, I went to, gave a talk at Imperial College in Oxford in the UK, Rick Doblin, you and I talked a lot and you made other introductions and I started expanding my mind about the potential for psychedelic compounds to lead to really profound and transformative outcomes through experience. That was the part that really captured my imagination. And then I started really reading Robin's papers carefully, and he has a lot of them. And he is,

Starting point is 00:48:40 you know, he's the most cited researcher in the field. And, you know, he's the most cited researcher in the field is known as set and setting, how you enter into a treatment, what is your makeup already, what are your intentions, and what occurs during it? What do you hear? Are you listening to music? Are there other elements of safety around you that take you through that experience to a certain outcome? And he's written about this both at their sort of review article level, where he's surveying the field, and then from work that he's done himself with music during treatments. they were therapists or shamans from South America or researchers at Hopkins. Everyone agrees that this element of context, that the experience itself is critical for the outcome, is universally agreed upon. I've never heard really any deviation from that. But the ingredients that go into the recipe of that experience that lead to the most favorable

Starting point is 00:50:06 and enduring outcomes is unknown. Now, there are definitely therapists that have experimented for many years with context and are experts in it. But if you're looking for prospectively designed randomized trials that have started dissecting these elements and learning who they work best for and what conditions, there's almost nothing in the literature that shows that. And so once I really realized that, I said, this is an incredible opportunity to make an impact in a field that already has so much potential and to really fill in that gap that I saw. And then it

Starting point is 00:50:41 was meeting Robin, finding each other, sharing this passion and realizing that we could do more together and that Neuroscape is a perfect environment in order to do this type of work because of the effort we already had in Experiences Medicine. And as you said, it seems like there's quite a bit of basic science that's been done. We have then the clinical trials, so advanced clinical trials, later stage clinical trials. But there is this, in a sense, gap in the middle. And there are people who will have context that they decide or assume or perhaps on some level even test to be effective that they take through trials, but they're not doing,

Starting point is 00:51:30 and this is going to be maybe a primitive way of looking at it, the sort of multivariate testing because they don't have the expertise or the equipment to do so, right? They don't have the team to do so. But you have a multimodal biosensing capabilities, multisensory integration work within Neuroscape. So I'd be curious to hear you speak to what capabilities you're looking forward to exploiting in the exploration and testing of these things. Yeah, let's dive into it. I just want to pause because we may have went over it a little fast. This sits in the middle between what? And I didn't really clarify that. So the reason I say it sits in the middle, and understanding what these compounds, LSD, the elements of psilocybin, what they're doing at the level of the cell. Are they anti-inflammatory? Are they plasticity-inducing? Really just the basic, what receptors they bind to,

Starting point is 00:52:39 an incredible amount of great work in that domain. And then on the other side, let's say the right, there is all the advanced phase two, now approaching phase three clinical trials. So these large multi-site trials with populations in need, like post-traumatic stress disorder and depression, alcoholism, end-of-life treatment, addiction, amazing clinical work showing benefit. And so the middle is all of the stuff that you need to go from the basic science insights into the clinical trials. That is the middle that we're talking about is missing. How do you optimize the delivery? How do you make it personalized to the individual? How do you make it precisely targeted to those neural mechanisms that most need to be improved. That's the area,

Starting point is 00:53:27 that's the middle that I see pretty much completely vacant. And that's the opportunity that excites us at Neuroscape that we want to explore. So I think I defined that area, that opportunity a little better. Let's dive into how do you do that? This is another intersection that I find fascinating and have for a long time is the role of technology in neuroscience and not just in the research, but in its translation. A perfect example is a video game as a technology that we have now used as a research tool and now have cleared as a therapeutic. How can technology play a role in understanding the middle, the role of set and setting in inducing a positive outcome? So there are really two ways that I'm excited about proceeding with that. And our team at Neuroscape is already proficient in

Starting point is 00:54:18 that. So we're quite prepared for Robin to land and then, you know, sort of hit the ground running, hit the ground running. Hit the ground running. And we're writing grants, we're buying equipment, we're already running, even though he hasn't arrived here yet. And so let's think about it this way. Here you are, you could imagine yourself going through a treatment like this at a university

Starting point is 00:54:40 and you're taking a compound, maybe you're familiar with it, maybe you're not, let's say psilocybin. and it's a reasonably high dose, you're going to have a pretty strong experience. And our goal is that you end up on the other side of the experience in at least the same place, hopefully a better place. Now, right now, if you were in a study with that design at a university anywhere in the world, you would likely be laying down with therapists. You would have already had several sessions, so you would have been well prepped. There would be that element of set of going into this. You would have been screened

Starting point is 00:55:16 for conditions that might interact unfavorably with this treatment, like schizophrenia and other conditions that are avoided, at least for now. And you would then ingest this and have usually a blindfold on, an eye mask, so it was more internal. You weren't seeing things. And you'd be listening to music. And that music would vary across site. It may not even be music that you actually like. But that is the design right now.

Starting point is 00:55:41 And then after, you would have the support during the session. And after the session, you would have several other therapist-led meetings to help process and integrate what you went through and then follow up. And that's the basic design. And it's a good one. And it's one that we've been really using for decades, even in the 60s, similar designs to this. And it's good methodology and it's getting better and better. What I see missing there in understanding the middle part is the first thing is we don't really know what's going on with a participant during the treatment itself. You're sort of a black box. Now, an extremely good therapist that has done this for 40 years is picking up subtle verbalizations or body movements or changes in your facial

Starting point is 00:56:26 expression. And they're able to protect you if you need it or help just sit with you as you go through some challenges. And that's as good as it gets. But that's not really scalable at any level because you can't have as many experts as there are people in need of a treatment like this. So that's the first opportunity. And I'm going to talk about that in a moment. And the other opportunity is a blindfold and a mask.

Starting point is 00:56:51 The best option is music. Really ideal? And what type of music? And what about all the other senses that we have, how we smell and feel and other aspects of hearing that are not being used during these treatments. Unknown. So used in the real world of therapy, but not really studied. We don't know who they're best in. So that's the second domain. So let's split those off. So the first domain is recording. So we have a system at UCSF we call multimodal biosensing. And my hypothesis is that with enough sensor technologies, not just looking at brain activity, but looking across the whole spectrum of physiology and behavior. So high density EEG, facial expression, electrodermal activity, heart rate and its variability,

Starting point is 00:57:39 looking at facial expressions, body movements, doing experience sampling either through vocalizations or using joysticks so that there is some degree of communication. My hypothesis is that not one single of those signals are going to tell us about the state of that individual during a treatment. But if we can collect them rapidly in real time and integrate them, use machine learning approaches so that we can look for the patterns of what's the most meaningful data, we will be able to plot the experience landscape of an individual traveling through a treatment like this.

Starting point is 00:58:16 We won't know the content. We won't necessarily know that they're picturing the details of a traumatic event in their lives. But I believe that we will be able to tell their level of arousal, the valence of it, is it positive or negative? So putting that together, their stress, the state of stress, their attention, whether their attention is internally directed or externally directed, as well as hopefully even a sense of their awareness of what's going on. So real-time state recording as implemented through multimodal biosensing. That's a very high-tech endeavor, but it is possible right now. It takes a real multidisciplinary team. So you're talking neuroscientists as well as people on the clinical side, biosensor technology experts, signal processing, machine learning.

Starting point is 00:59:08 It is a real challenge and it has not been accomplished yet anywhere in the world at any level that allows us to really track state. So that's the first challenge that we want to really tackle is using technology to understand the state of the person while they go through a treatment. The other side of it is starting to manipulate all of these levers of context of the setting and the set. So how do we position them through different information that presented different environments before the treatment? And then during the treatment, not just think about music with eyes closed. Sure, we will do that. That is the standard approach right now. But what is it like to look around you, to see either light or abstract views or views of nature, to smell a forest when

Starting point is 01:00:00 you see it and when you hear it, what we call multisensory integration, to feel low-frequency vibrations through your bodies as you enter into these different environments, all of that is unexplored. And so by putting these things together, we start understanding the journey, the journey within the treatment itself, how these little, you know, not little to the individual, but these discrete moments in time, these micro experiences along the way, how they're influenced by the context of the environment that we're able to control around the participant, and then how all of these elements add up to an outcome, to a sense of well-being or joy or mystical perspective that occurs after. So how do we connect the events that occur during the treatment with the outcomes? All of that is

Starting point is 01:00:54 unexplored. And that's basically what we're going to be focusing on. There is so much room for experimentation. So many variables. There's a lifetime there. I always say to Rob and I was like, we will die before all that that you just heard is figured out. There's so much. It's incredibly exciting to me for many reasons. And just to give a snapshot of personal experience here that raises questions, I think, related to those that you'll be exploring in a very methodical, tech-enabled way so that you can actually measure, capture, and quantify these discrete events, discrete changes. I recall the first time I did a five-session series of infusions.

Starting point is 01:01:43 This is intravenous infusions of ketamine. And in this case, I wasn't using it because I was suffering from acute depression nor chronic pain. Those are two indications. But I wanted to be able to speak to the effects and possible side effects, after effects of ketamine treatment if I were asked, which I knew I would be asked. And what really stuck out to me, among other things, in this ketamine treatment, that it was the first And I was able to choose a DVD that I then used as a constant throughout my sessions. I didn't change the video because I didn't want that to be an uncontrolled variable. And I'm not pretending that these are really tightly controlled, but I was trying to minimize the number of variables. So I kept this constant as this video. And I'd never in a deep psychedelic experience, which you can certainly have with

Starting point is 01:03:01 ketamine at sufficient enough doses, even though it is a bit bizarre as a dissociative anesthetic. I'd never had the experience of attempting, even attempting to watch video in these days. So to observe how the imagery, and this isn't, I suppose, on some level surprising because internally generated imagery can certainly have a tremendous effect. But to observe how the imagery affected the experience, how the music on the video affected the experience, how closing my eyes or opening my eyes while being exposed to this external stimulus affected my experience was very new, right? It was very novel to me. That's not what usually happens. If you are in a supervised setting, certainly within a university context, right? It was very novel to me. That's not what usually happens if you are in

Starting point is 01:03:45 a supervised setting, certainly within a university context, right? It's more or less what you described. It's like, okay, I fold on, lay down. We have pretty good evidence to suggest that this at least doesn't interfere with reasonably good outcomes, but there's so much fine-tuning and assumption testing that can be done and that you will be doing. It's incredibly exciting to me. That's great to hear. Yeah. When I first started putting the meat on the bones and saying, okay, this is something

Starting point is 01:04:15 exciting. Robin's interested. My leadership at UCSF is behind me creating this. I felt nervous because this is a new field to me, and it has a lot of history, right? There's a lot of therapists that have been doing this for decades, and obviously, the indigenous cultures around the world have used these as not just mental health tools, but as religious and spiritual. And I wanted to dive into that part and determine if anything that I have just said to you is offensive to them. I just was curious how it would be received because it is very, very different than

Starting point is 01:04:55 how these experiences are often delivered throughout history. And I was really surprised to find that, especially on the multisensory stimulation side, therapists that I talk with were really receptive to it, that they thought that this is actually what they mean when they say shamanism. It is this act of environment tuning and creating to help guide that journey. And they feel that they're maybe pretty good at it because they've been doing it for a long time, but they were certainly open to having data that they could reach for that would give them more fine tuning and also recognizing how hard it is to train people that are new to this. And that if there was a library of stimuli and evidence of who it works and how it works, and also

Starting point is 01:05:48 their ability to know what's really happening inside an individual's mind, they were very, very activated by that. Now, I'm sure that won't be true for everyone, but that was really reassuring. And the last point I want to make on this was my big goal here is not to say we don't need therapists anymore. We don't need humans in the loop. We have enough technological advancements in terms of sensor technology and machine learning and artificial intelligence that we're good. We just need you to take this step into the box and come out fixed. And I really actually do not believe that that is the future we will or should have. I think that what we're doing here is building a set of tools, really sophisticated, informed, data-driven tools that will allow a therapist or any practitioner in the space to be more effective at helping their patient.

Starting point is 01:06:47 That is what I hope and believe will come from this long journey. And that technology will be what it always should be. Is it just another human tool? So that's where I hope and do believe that we will end when we go through this research approach. Looking at Akili and Endeavor RX for a moment, because I'm tying these things together in my own mind, I'd love for you to stress test what I'm about to say in treating not just children with ADHD, but patient populations or populations with autism, with depression, these different conditions, and talking about how it is possible

Starting point is 01:07:27 that a single intervention can be efficacious across multiple conditions. This conversation or related questions translates quite well to the study of psychedelics. And certainly Robin Carr at Harris talks a lot about the default mode network and how and why it appears that some of these compounds are therapeutically effective, or at least appear to be. The data suggests that they are effective across a pretty wide range of conditions that most or many people would assume are not related at face value. So you have different types of addiction, including alcohol use disorder, opiate use disorder. That's opiate use disorder forthcoming at Hopkins. And then you have PTSD.

Starting point is 01:08:18 You have treatment-resistant depression, as well as major depressive disorder. There are people looking at OCD. And the assumptions of which, or one of the assumptions underlying the cross-efficacy is that perhaps there's this commonality, this common kind of neurological correlate with the default mode network, that there's a rigidity associated with these various behaviors that is attenuated with psychedelics. So I'm just, in my own mind, observing a similarity between the software development and then the testing within psychedelics we'll be doing. The question that I have is, do you envision looking at how much is automatically achieved with software, there's an adaptive component where you are able to determine over time for a single subject,

Starting point is 01:09:19 a sequence of experiences that is adaptive in some way. Does that make sense? Yes, it makes total sense. You mentioned this earlier, and just in case some listeners didn't catch it, Endeavor RX adapts to the user, right? It's kind of like a personal trainer who increases the weights in certain movements over time. So you have progressive resistance and therefore greater adaptation. Do you think that that is an area you'll be exploring or that you would like to explore how you can adapt a series of psychedelic experiences for an individual to be customized?

Starting point is 01:09:57 Undoubtedly. It was really, really a great statement and question that I want to just take a moment and unpack from my perspective, because I think as we've had this conversation, people could be lost of, wait, are you building video games? You're working on psychedelics? Where are the threads here? It is the same thing that we're talking about all along. This is the power of experience to change the brain, what in neuroscience would be known as experience-dependent plasticity. Whether that experience occurs with or without a molecule, it has the power to transform you in an incredibly profound way. And it could be positive or it could be negative. That is what PTSD is, right? You could just witness something so horrendous that your brain functions differently from there on out, right? That is the negative side of this story. That is what I've been working on, how to build

Starting point is 01:10:57 experiences. We do a lot of work with virtual reality now, multisensory experiences, I believe will have even more profound outcomes and more transformative effects. And we don't put any compounds on board, right? That's what Neuroscape basically does now. Now, expand the conversation. And we're talking about these psychedelic compounds, and there's a broad array of them. So we won't break them all down, and they're all different in some way in the effects they have. But they really have these two features that are most fascinating to me. One is that they shuffle the deck, right, in many ways. They break down the rigid sort of frameworks that you go into the experience with.

Starting point is 01:11:43 And that is a combination of changes in default network. And also, there are many networks in the brain, big, large-scale networks, and their interaction leads to you and leads to your consciousness. And so, those are shifted, leading to the opportunity to reform them. Adam, let me just pause you for a second. When you say they lead to you, that means your conception of self? Like when I say, I am Tim, is that what you mean? Yeah. From every level, your ego, your reflection of your identity, but also your position in space and in time and your relation to other elements of the universe and the world around you, all of that is fluid, more fluid. And that is because these networks that may

Starting point is 01:12:28 dictate your own reflection of who you are or how time is passing or how you perceive light or sound or touch are distorted from the norm, thus allowing a complete rediscovery of you and the world around you. That's one very profound piece of it. And the other is that they induce neuroplasticity. And Robin talks about this all the time when he presents his work. And that is also incredibly fascinating because it's not just that these compounds enrich or change an experience, which they clearly do, they also are plasticity-inducing, meaning that the changes that occur have a greater potential to endure. Now, this would be really a bad thing if you have a negative experience, which is, I think, part of what has occurred over the last half century is realizing that in an uncontrolled environment that you may be threatened while on a compound

Starting point is 01:13:32 like these, the effects can be way worse than if you were not on them. So this is the yin and yang, the plus and minus that everything has, is that we now realize that the experience, since that is what evokes the outcome, needs to be positive, or at least, not that suffering can occur, but at least needs to be nurturing in a way that leads to a positive outcome. So I just wanted to make that connection is that it's really about experience and large-scale neural networks that cross multiple domains and plasticity. And that is the common feature that unites all the work that we do at Neuroscape, whether it's non-invasive brain stimulation, new approaches to neurofeedback, video,

Starting point is 01:14:16 closed-loop video game technology, or now psychedelics. So just to put that together, because you made the leap between Endeavor RX and this work. And now to just answer your question more specifically about closed loop systems. So let's just pause and just make sure that everyone's on the same page with that. So probably what makes Endeavor RX so unique, as well as the dozen other video game technologies that we have at Neuroscape, from MetaTrain to Engage, Labyrinth, we just had a paper on, Body Brain Trainer, they're all closed loop. And what that means is that real-time data about your state, and it may be very simple data like your performance data, how fast or accurate

Starting point is 01:14:57 you are, feeds into a processor, a computer that records that data, makes a decision about it, and then updates your environment, the challenges that you're experiencing, the stimuli, the rewards that you're being exposed to. And it goes on and on, constantly adapting. That's why I made the analogy to a personal trainer. Imagine going to a gym and having a trainer that has access to every aspect about you in the moment and also this ability to change things so subtly to just push you to the know, some of them are eyes closed, meditative experiences. Others are rapid, fast paced action experiences, but that's what we do. Now let's talk about psychedelics. So I described to you a system where technology enables multimodal biosensing. So we can understand your state in real time. And I described us having the ability to change what you see, hear, smell, and feel. And so we have the two sides.

Starting point is 01:16:13 We have the ability to know what's going on with you, and we have the ability to shape your environment. What we didn't talk about is what you just said, creating a closed-loop psychedelic experience. That is the goal here, that we can have, let's say, a therapist sitting in front of a patient or a participant in a research study, having access to this data. Maybe they have to, if you want to be science fiction here, picture them in virtual reality watching a four-dimensional representation of your experience,

Starting point is 01:16:42 of their patient's experience unfold to see, are they in high stress? Are they suffering now? Okay, it's okay for them to suffer, but only for 15 minutes because our data shows that after that, then it starts becoming more likely to cause harm than to help. And so they're watching this unfold and then they have these tools, right? They can say, oh, this is the time where it's worth to move out of this high stress, deep internal attention, high arousal, high awareness moment, and bring it out. And in order to do that, what I'm going to do is move them into a forest where they could smell pine and hear a waterfall and feel low frequency vibration across their body. And that will ease

Starting point is 01:17:27 them out. And then we'll have another day where we can go deep again. This is the closed loop. We're using real-time data, and it can be done just with machine learning itself and a processor or a human on board like I just described. That's how we could create personalized experiences that are targeting those aspects of their brain function that need to be improved whether they're suffering and they have a pathology or they're just trying to enhance and elevate their minds just imagining an electro facilitator with a within some type of minority report, like virtual reality, grabbing stimuli, adding them or subtracting them, combining them, like the Swedish chef adding ingredients. It's quite a picture. It's quite a picture. And you say science fiction, but I think these things may end up being closer than people anticipate.

Starting point is 01:18:26 And furthermore, I just want to say that the research you'll be doing, the experimentation brings up, I find this tremendously exciting, so many challenging questions. I'm not going to say problems, but so many challenging questions. For instance, you just alluded to this, but when does it make sense to increase or expose someone to increased stress? Speaking just end of one, actually it's more than end of one because I have friends who would share this opinion that many of, I'll just speak for myself, many of my most positively impactful experiences with psychedelics that had positive, durable effects were very challenging experiences in safe environments. And so determining what the appropriate dose of distress is, if there is one, is such a fascinating question. Because there is a point where the dose makes the poison and all of a sudden someone comes out and they're destabilized for two weeks or potentially longer longer right so where how do you thread that needle it's very

Starting point is 01:19:46 hard to even if sorry to to run around but please go but even if an experienced say indigenous healer could intuit that and do it effectively while that is incredibly impressive, it does not increase the availability of psychedelics as a therapeutic tool because that is a spider sense or some innate or trained ability that takes a very long time to develop. So you can't just copy and paste it. But if all of a sudden, like you said, you have this library of data, you have evidence to suggest where the tipping point is and when you should introduce that forest, I mean, even repeat it. You said it perfectly. It would be silly. I mean, that is exactly what has excited me here. And then when I found out that those therapists and indigenous shaman, they were like, yeah, we would like to know that data too, you know, like even the experts. really lit up by is talking to those individuals, allying with them and saying, and I've done this several times now, and it's so much fun to say, okay, you've been doing this for 40 years. When you're sitting in front of someone, how do you know if they're suffering? And when do you decide to help them out, to lay hands on them or to introduce some sense, which is what they do?

Starting point is 01:21:24 And they will talk about, and I'm taking notes, they'll be like, well, I could see their face change. I'm like, perfect. I could record facial expressions pretty easily with either a camera or an electrode. They'll be like, well, sometimes they vocalize. Also very, very accessible to us right now. And so that's what's really fun about designing these research studies is not doing it from some academic halls and even resting on the scientific literature itself, because a lot of this is not recorded in papers. But it's out there in the world in true life wisdom and expertise that's been accumulated over sometimes centuries. But finding those nuggets and then using the tools that I described

Starting point is 01:22:07 and doing very carefully controlled research studies that would be accepted by even the most conservative of regulatory agencies or professionals out there to move this forward. And as you said, to make it accessible, there is not nearly enough experts in the world for all the people in need. I mean, not even by an order of magnitude. So we have to figure this out or this is just going to be a tool for the elite, right? And just won't have the access that we need it to. One thing I really appreciate about you is, and with respect to this area, I wouldn't

Starting point is 01:22:42 say in particular, but it's a good example. You've spent an incredible amount of time, and I know this because we've had so many conversations over the last few years, with practitioners who operate with different compounds in many different environments, with different populations, in different geographies, who have stylistically different approaches. And you have, as you mentioned, not sequestered yourself in this ivory tower of literature as your sole source of input. And one challenge within the psychedelic community is that there's no such thing as a psychedelic community. There are, in fact, what I would consider factions, in a sense. I mean, you have kind of the scientific group. Now, by scientific, let me qualify. You have

Starting point is 01:23:33 scientists, people who are actually doing the work. You have well-educated folks who are secular, who succumb to a certain degree of scientism, I'm not sure what you would call it, but those who aren't really scientifically literate but view it dogmatically almost like a religion. Then you go all the way to the other side. You have people who might embrace indigenous traditions or some hybrid, say, neo-shamanic approach along the lines of, or Western psychotherapeutic approach along the lines of, say, a Leo Zeff or a Stan Grof. And there's a lot of friction amongst these groups. I'm not surprised on one level because humans are humans and there's a lot of kind of tribal impulse readily available at any moment. But to what would you attribute people thus far in your experience

Starting point is 01:24:27 from these many different worlds? And there's a whole spectrum. Being open and interested in the work that you're doing. Because my experience has been that very often, the scientists don't really want to embrace indigenous or facilitator wisdom and view it as hocus-pocus, hand-wavy, woo-woo, superstition. And then on the flip side, you have the people who are on the not necessarily indigenous side. I actually find a lot of the indigenous people who have a lineage of this quite open-minded, but sort of in the neo-shamanic space, are very dismissive of scientists and view it as overly reductionist and missing the point on some level. Long question, but why do you think people have responded so positively to you? I think because at the fundamental level, everyone recognizes that this is experiential medicine. And that is how I start the conversation. I don't know the

Starting point is 01:25:26 best experience to lead to the best outcome. And I'm not approaching this in a very rigid way of, this is the approach that I think is going to lead to the best outcomes. I'm just suggesting that thinking about this as a drug from the point of view of molecule leads to effect. You take this antibiotic, the biote is killed, you're better. That's not what we're talking about here. We're talking about the creation of an experience that is undoubtedly induced or accelerated or enhanced by these compounds. But the nature of the experience leading to outcomes, I think everyone agrees upon that basic framework. So if you enter the conversation with that as the ground truth, I think that there is a lot more likelihood of reaching at least a commonality of view that,

Starting point is 01:26:28 don't we want to understand the experience more? Don't we want to be able to guide? Some of it's just language. The word control, which we, okay, but the word guide is a lot more favorable. Now, we're sort of many times, not all times, talking about similar things there. We're not talking about pushing you into this place. We're talking about presenting you with options to enter this place. And so some of it is just being really very careful about language, understanding the person's perspective that you're talking to, being respectful of the amount of time and expertise they have. And then just returning to the ground truth that this is an experiential medicine and there's so much more we could learn in order to help more people. And that is where I find that there's a great commonality. Well, Adam, I couldn't be more excited. I'm going to ask you in a minute

Starting point is 01:27:34 what the future looks like and how people can help, certainly, and where they can find you. And I have those notes in front of me, so not that you would need me to remind you of your own URLs. But before we sort of wind to a close for this conversation, is there anything else that you would like to say to my audience, to a request of listeners, question you would like to pose, anything at all that you would like to say before we get to the question of next steps and how people can help if they would like to help? Yeah. I mean, just at a high level, I would just like to remind everyone that to keep an open mind. You might have heard things that we've talked about that are completely in your wheelhouse, that you're just so fired up. That's exactly what I love, and others that

Starting point is 01:28:32 might feel threatened by it or that it's distorting the real value of these medicines. But I just encourage you to keep an open mind and realize that the underlying goal here is that there is so much suffering in the world, and we have done such an atrocious job of addressing that. If you look across the fields of cardiac health and infectious disease, despite the fact that we're in a pandemic now, we've done so much better than we have in terms of mental suffering. And the idea that there's a magic brain pill out there that's going to fix it is just not going to happen. It's not true of these compounds either. We have to be really creative in how we think about treatments and

Starting point is 01:29:15 how we use science and technology to get there. So I just encourage people to keep an open mind. You don't have to agree with everything you've heard, but the need is great and the opportunity is here now. So I thank you for your patience in listening and going on this journey with Tim and I. Neuroscape.ucsf.edu. Just to reiterate, I'm so optimistic about this new chapter within Neuroscape and for you also. I mean, this is a big commitment for you for a multitude of reasons. And I think a lot of people will be similarly excited and galvanized by this. So you have UCSF, which is from a science medicine research perspective, as blue chip

Starting point is 01:30:03 as it comes, it is not an institution that has been heavily associated with psychedelics in any way previously. Your lab has also not been associated with psychedelics previously. And I think that it will hopefully inspire many people to take a close look at these tools, these medicines and research associated with it.

Starting point is 01:30:27 I think it's going to be incredibly validating for the space. And for that, I'm incredibly grateful. How can people help? What are some of the next steps? Are you looking for financial support? What are you looking to do and what do you need to do it? Yeah. We need a lot of help, right? It takes a village and we have great people on board already. Jenny Mitchells is leading a site for the MAPS trial at Neuroscape in our division right now.

Starting point is 01:30:54 So we already have some early momentum. Robin, of course, is coming on board and couldn't be more excited by what he's going to add to this. So we have a great team and we have UCSF support, but we need a little bit more of everything. So there may be listeners that have experience with the perspective that I just shared in terms of the experiential, the set and setting. They might have it from personal experience. They might have it as a

Starting point is 01:31:23 practitioner or as a scientist. From any viewpoint, I want to hear about it. We want to be informed. And as we talked about, Tim, not just based upon a literature, but based upon all of this real-world data that has accumulated over time. And so that is one need right there. Just educate us. How would you like to hear about it?

Starting point is 01:31:44 Is hitting you on Twitter, is there an email that is not going to bury you forever? Yeah. Well, on gazali.com, there's a contact site and that would be a great way and I'll share with my team. And so, yeah, so, you know, we want to be educated. And one of my sort of tenets is not to just think that we know everything. And in this case, none of us want to be educated. And one of my sort of tenants is not to just think that we know everything. And in this case, none of us do, no one. And so the contact information on there and the way to offer that perspective to us is open. We probably won't be able to reply to everyone, but you will be heard and that information will be shared and it could

Starting point is 01:32:20 help inspire research and our own perspectives. So website, gazaley.com. Correct. The next is financial support. We have done well. We have over $6 million in funding, which is enough to get Robin here and supported and to build out our first set of studies and to hire some great postdocs and bring on some junior faculty. But it doesn't go

Starting point is 01:32:45 that far when you're talking about the type of division that I just described to you and the research objectives we have. So there's lots of opportunity. We want to build a new cutting-edge facility at Neuroscape with multiple laboratories so that we can do more research more rapidly. And so philanthropic support is always welcome at any level. And again, you could contact me through there. There's also contact on Neuroscape's site if that's more palatable to you. Whatever way you want to reach out and let us know

Starting point is 01:33:18 if you would like to be part of the funding of this endeavor would be incredibly appreciated. Do you have a target raise amount that you're able to disclose, or would you prefer not to have any specific number as a target? When I first formulated this and then put the team together and we brainstormed about what we wanted to accomplish over the next five years in terms of building the team, in terms of having the research tools that we need, in terms of building the facilities, because we have space to actually create some new labs, very cutting edge labs that bring this type of technology, but not in an intrusive way to maintain the natural feel and the warmth. That's tricky.

Starting point is 01:34:04 So there's design challenges. In order to accomplish that, our goal was $20 million. So we have a ways to go. Now, adding $10 million right now would allow us to actually build the facility. That will unlock a massive amount. So that's sort of what I've been keeping in my mind when I look towards what I hope that we'll accomplish over the course of this year. believer, huge believer in you, Adam, and Neuroscape and have been for a very long time. So I am also, through my foundation, contributing some capital. And I would imagine that people can donate appreciated securities, i.e. stocks and possibly other things. Do you know if UCSF is able to receive cryptocurrencies of any type? It's a great question.

Starting point is 01:35:06 This would be a good time to investigate that. Yeah, that is a great, great question. And I will find out later today. Wonderful. And I know that you and I have the mutual acquaintance of Rick Doblin. MAPS has in the past figured out ways to accept cryptocurrency. And in fact, some of their largest donations have come from Mr. Apple, maybe Mr. Pineapple, as he is known, through, I believe it was Bitcoin, but through cryptocurrency. So this would be good to investigate.

Starting point is 01:35:38 And if you are able to do that, or if there's an approach to that, we can put it in the show notes at Tim Knott blog slash podcast for people who may be interested. This just in, breaking news. Yes, UCSF can now accept cryptocurrencies for Neuroscape and the work that Adam will be doing. I believe this could be a first for a major university. It's a very big deal. And I'm supporting his work. If you would like to support his work through cryptocurrency, you can do that. And all you need to do is email neuroscape at ucsf.edu. That's N-E-U-R-O-S-C-A-P-E at ucsf.edu. And they can provide you with instructions for how to do this. And now back to our conversation.

Starting point is 01:36:26 Adam, I'm excited for you. I'm excited for the our conversation. Adam, I'm excited for you. I'm excited for the future of this field. I'm excited for your team. I'm excited for Robin and the people not yet determined who may contribute or join the team in some fashion. And I really appreciate you taking the time to hop on the phone, especially looking like old man time. You have a big beard right now, which suits you. I like it. I like it. And for those who are wondering about the visual, Adam has been, I don't know how long you've been the silver fox. I mean, you have- Since college, pretty much. Since college. I mean, you look kind of like, I mean, not exactly, but like Storm from the X-Men. You have perfectly white hair, luscious locks of white hair, and now you have in this, your support over the years,

Starting point is 01:37:30 not just financially, but in every way. You've been a great friend and a great colleague to have on this journey. And it's just, I'm buzzing right now at how much fun I had just going down memory lane and then looking to the future. So just, I know your listeners already appreciate what you bring. And I have my own perspective as being a longtime friend. And I just want to thank you for always giving all of my ideas an outlet and your attention and then helping to share it with your listeners. So thank you so much. Oh, thanks, Adam. I love you and your family very much.

Starting point is 01:38:02 I can't wait to give you a proper hug in meat space. This virtual shit is for the birds. I'm just saying. I agree. We'll get there eventually, and hopefully in a few months, in fact. And I can't wait until we can actually break bread and have a drink together. I look forward to that, too. Thanks again for taking the time.

Starting point is 01:38:26 And to everybody listening, this is exciting stuff. Check Adam out, gazali.com, as mentioned, G-A-Z-Z-A-L-E-Y.com, Neuroscape, which honestly, even if you have zero interest in psychedelics, just for the other work that they've done, neuroscape.ucsf.edu is well worth checking out. It is a glimpse of the future. As far as I'm concerned, you can find them on Twitter at AdamGazz, G-A-Z-Z, which is also the handle on Instagram and Facebook. We will have show notes for everything, including hopefully an update on whether or not Neuroscape and Adam can accept cryptocurrencies because

Starting point is 01:39:05 Adam makes and his team make incredibly capital efficient use of funds. They are like a lean, fast-growing, well-executed startup. That is part of the reason I've been so enthusiastically supportive and I encourage people to take a look. And so we'll have links to everything at Tim.blog forward slash podcast. And thanks for tuning in. Hey guys, this is Tim again. Just a few more things before you take off. Number one, this is Five Bullet Friday. Do you want to get a short email from me? And would you enjoy getting a short email from me every Friday that provides a little morsel of fun for the weekend?

Starting point is 01:39:49 And Five Bullet Friday is a very short email where I share the coolest things I've found or that I've been pondering over the week. That could include favorite new albums that I've discovered. It could include gizmos and gadgets and all sorts of weird shit that I've somehow dug up in the world of the esoteric as I do. It could include favorite articles that I've read and that I've shared

Starting point is 01:40:12 with my close friends, for instance. And it's very short. It's just a little tiny bite of goodness before you head off for the weekend. So if you want to receive that, check it out. Just go to 4hourworkweek.com. That's 4hourworkweek.com all spelled out and just drop in your email and you will get the very next one. And if you sign up, I hope you enjoy it. This episode is brought to you by Allform. If you've been listening to this podcast for a while, you've probably heard me talk about Helix Sleep and their mattresses, which I've been using since 2017. I have two of them upstairs from where I'm sitting at this moment. And now Helix has gone beyond the bedroom and

Starting point is 01:40:49 started making sofas. They just launched a new company called Allform, A-L-L-F-O-R-M, and they're making premium, customizable sofas and chairs shipped right to your door at a fraction of the cost of traditional stores. So I'm sitting in my living room right now and it's entirely Allform furniture. I've got two chairs, I've got an ottoman, and I have an L-sectional couch. And I'll come back to that. You can pick your fabric. They're all spill, stain, and scratch resistant. The soap color, the color of the legs, the soap size, the shape to make sure it's perfect for you in your home. Also, Allform arrives in just three to seven days and you can assemble it all yourself in a few minutes. No tools needed. I was quite astonished by how modular and easy these things fit together, kind of like Lego pieces. They've got armchairs, love seats,

Starting point is 01:41:34 all the way up to an eight seat sectional. So there's something for everyone. You can also start small and kind of build on top of it if you wanted to get a smaller couch and then build out on it, which is actually in a way what I did because I can turn my L-sectional couch into a normal straight couch and then with a separate ottoman in a matter of about 60 seconds. It's pretty rad. So I mentioned I have all these different things in this room. I use the natural leg finish, which is their lightest color, and I dig it. I mean, I've been using these things hours and hours and hours every single day. So I am using what I am sharing with you guys. And if getting a sofa without trying it in-store sounds risky, you don't need to worry. All Form sofas are delivered directly to your home with fast, free shipping, and you get

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Starting point is 01:42:51 That's allform.com slash Tim and use code Tim at checkout. This episode is brought to you by ExpressVPN. What is VPN? Virtual Private Network. It's an app that you run on your computer or your mobile device. It secures your internet connection, hides your public IP address, and lets you bypass regional restrictions on content. And I actually asked my followers on Twitter, 1.5 or 1.6 million of you, for VPN recommendations, your favorites. Many wrote back that ExpressVPN was their favorite, including a number of people who've been on this podcast. So I gave it a shot and it is ridiculously fast to the extent that I thought

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The Tim Ferriss Show - #507: Dr. Adam Gazzaley, UCSF — Brain Optimization and The Future of Psychedelic Medicine

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The Tim Ferriss Show - #507: Dr. Adam Gazzaley, UCSF — Brain Optimization and The Future of Psychedelic Medicine

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