I'd like to ask you about another area where you really have seemed to see around corners. And this is one that actually carried with it significant risk. Not necessarily risk to health and to life, but risk in terms of outside perceptions. And that's psychedelics. As you know, I've substantially changed my view on this.

We don't need to go into my former stance on it. And I talked about that when you were gracious enough to host me on your podcast for a second time, done some psychedelics recreationally as a kid. It was correlated with not so great times in my life, stayed away from them, then eventually revisited MDMA in particular from a therapeutic standpoint, found tremendous benefit.

Again, therapeutically with a medical doctor. Again, these drugs are illegal, soon to change perhaps, hopefully. And we'll talk about that. But it's becoming clear from the controlled studies by Robin Carter Harris. There are many others, Nolan Williams, others, that these drugs have enormous potential to help relieve depression, trauma, help people explore their psyche, their mind, for sake of feeling better, doing better in the world, for leaning into life, not tune in, drop out, but to really lean into life with more purpose and more satisfaction.

In some cases, they've really have saved lives, I think. What was your mindset around psychedelics when you first started exploring them? What led you to overcome the inevitable fear gap there? Because you do seem like somebody who takes value in your health, right? You're not reckless. You may have been more adventurous in the past with things like, I hate the word, but biohacking and self-experimentation than you are now, but you obviously have some self-preservation mechanism intact.

- We learn, we learn. - We learn. What was your mindset around it at the time? And then I want to get to what you've learned from it. And frankly, the tremendous efforts that you've put that are now translating to tremendous value for really millions of people. And ultimately, I think it's going to be billions of people by establishing funding for the pioneering research in this area, helping to promote the movement of these compounds from illegal to legal in the therapeutic setting, so on and so on.

So take us back to your first thoughtful exploration of psychedelics. What'd that look like? You're like, oh, mushrooms, I'll eat them. Was that it or was it a dedicated research process? And who'd you talk to? What was it all about? - So let's go way back to my undergrad experience.

And there were many reasons that I ended up going to Princeton. I think I was very lucky to get in. My SAT scores, because I could never finish the damn test. I was so much of a perfectionist. I'd get stuck and ended up not doing terribly well, but through essays and other things, ultimately was able to go.

Part of the draw for me-- - Well, let me interrupt you and just say, I think at this point we can say they were lucky to have you. - Well, thank you for saying that. Thank you for saying that. - Great institution. And you've done great. And you're a great poster on the wall for them.

- Oh, really? - I hope so. - Really, really. Yeah, I just want to say it, 'cause you're not going to. And I think it's important that these are great institutions that great minds go through there. And Einstein went through there. And their success rests not just on the Einsteins, but also on the student body and what they go out into the world and do, and not just in the realm of science.

So really, they're lucky to have had you. - Yeah, thank you, Andrew. I studied Chinese in a room where Einstein used to teach. It's pretty cool to set foot and spend time weekly in a space that was shared by some of these people. - Amazing. - It really gets the imagination firing.

If we go back to that chapter in my life, I was initially a psychology major with a focus on neuroscience. So I wanted to be a neuroscientist. And there are many reasons for that. I have neurodegenerative disease on both sides of my family, so Parkinson's and Alzheimer's. So that was certainly a personal driving interest in terms of looking at mechanisms, understanding what therapeutics existed or did not exist, how things were developing in the research.

And while I was there, which later I ended up switching gears and transferring to focus on language acquisition and East Asian studies, hence the Chinese that I mentioned earlier and Japanese and Korean. But on the neuroscience side, there were a lot of cool breakthroughs also that came out of Princeton around that time, looking at the amazing discovery of, say, neuronal, I don't wanna say regenesis, but neurogenesis in the hippocampus.

- Yeah, Ms. Gould's work. - Exactly, exactly. So there was quite a bit happening at that time. I was a subject. I loved volunteering for studies just to try to get an inside look at how things were done in some of Daniel Kahneman's experiments. So it was a cool time to be there.

And within the first two years, I wanna say, I had my first experience recreationally with mushrooms. And looking back now, I'm horrified by the lack of control, and meaning not control, but lack of supervision, right? I mean, the setting, the set and setting ended up being fine. Nothing terrible happened, but there were a lot of ways it could have gone sideways.

But that first experience, and I must have consumed in retrospect just a dizzying amount of mushrooms. - This would be in excess of five grams. - It would have been more, yeah. Just knowing what I know now, it would have been pretty-- - Kids don't do this at all.

- Don't do that. - I'm not gonna say don't do it at home. Don't do it at all. - Yeah, yeah. - Please, I actually don't think the young developing brain should be exposed to psychedelics. - We can talk about that. - We can talk about that. - Yeah, we can talk about that.

- I'm gonna take my stance. I'm gonna take my stance for now. - Yeah, I mean, in the world in which we live, in the US, I would totally agree with you. There are some interesting cultural exceptions in other places where things are more set up to provide for that type of use, but I certainly would not recommend it.

But coming back to my recreational experience, my subjective experience was so bizarre, and my experience of time so nonlinear, my experience of self so different from anything I had experienced up to that point, and therefore my construction of reality being so completely unlike anything I had experienced was enough to make me want to learn about these compounds.

And very early on, I still have a scan of it somewhere. I think it was in 1998 or '99, I actually wrote a paper. One of my junior papers was focused on examining potential similarities between REM sleep and LSD, LSD-25, and looking at some of the patterns of neural activity.

Of course, we can do a lot more now with the tools that we have available, but from a scientific perspective, I was very curious about how much we knew and how much we didn't know. And I would say that latter category gets me more excited in a way. And I'm like, okay, how much room is there for growth here?

Because if we're just putting on the finishing touches with marginal, incremental improvements on something that we feel like we've largely figured out, that's less interesting to me than something that baffles most people examining them on some level. And there was a professor named Barry Jacobs who was doing some very interesting work.

He did a lot of work looking at the serotonergic systems and did a lot of work with cats. Ultimately, I could not do personally the animal work required of the sort of indentured servitude that I would take home. - I think you wrote someplace once, you said when confronted with the prospect of installing a computer printer into the head of a cat.

- A printer jack. - A printer jack. - On the back of a cat head. - On the back of a cat head. - They literally had those little VGA ports on the back of these cats' heads, because cats sleep a lot and so they're interesting to study. - Very few laboratories work on cats any longer.

It's mostly a mouse, still some non-human primate work. My laboratory is essentially shut down or is in the process of shutting down even our mouse work. I much prefer to work on humans. They can give consent and they house themselves. The animal research thing is tough. For any sentient being, it's tough.

- For what it's worth, the cats seem pretty happy. They were just sleeping. I mean, the ports were for tracking. So the cats were pretty, I mean, they were just normal cats. The cats were fine, but I would have been, we would have been injecting retroviruses into rats and then perfusing them, which means bleeding them to death to avoid bruising of the tissue, because then if you're gonna take thin slices and scans, you didn't want to have bruising.

And I just couldn't do it. I think it's important. I do think, I do think there's a place for it, but I couldn't do it. So that's why I transferred out. But the point I was trying to make is that I had the experience and then I had that drive, the scientific interest.

And then I had probably one experience per year for a few years after that. And what I noticed for myself personally, because I suffered from major depressive disorder and extended depressive episodes, let's just say on average three to four a year. And by extended- - Even before you had started all of this.

- Oh, even before, yeah. - From a young age. - Yeah, from a very young age. And I would say, so let's just call it three to four on average a year. Those could last each a few weeks or a few months. I mean, this is a very high percentage of my total year.

And when I had these higher dose experiences with mushrooms, so we're talking about psilocybin mushrooms. And then if we're looking at the molecule that's being examined scientifically, psilocybin, I noticed this afterglow effect that was really durable. And that was an antidepressant effect or a mood elevating effect that lasted far longer than the half-life could explain.

Four to six hours, you're kind of on the other side. And I would experience this afterglow effect for three to six months. And that raised all sorts of interesting questions. What the hell is going on here? Is it the content? Is it some structural change? There were a lot of unanswered questions for me.

And then I had a very, very scary experience that led me to completely stop use of psychedelics where, again, uncontrolled environment, ended up in rural New York, coming out of my trip, standing in the middle of the road in the middle of the night with headlights coming at me.

- Goodness gracious. - So you don't wanna do that. And I was like, okay, too dangerous. - Were you taking them alone? Is that how that is? - I was taking them with two friends and my two friends, without telling me, just went for a walk and left me alone.

So don't do that. - It points to the, I mean, these are powerful compounds. - Yeah, you're playing with nuclear power. Like these are the, this is the nuclear power of psychological or psycho-emotional surgery is the way I encourage people to think about them. And I stopped using any psychedelics completely.

I was still very interested in them, but I basically hit pause. And I didn't revisit that until, let's call it 2012, 2013, where I was still struggling with major depressive disorder. And I saw my girlfriend at the time completely transformed by supervised facilitated use of, in this case, ayahuasca, which was not quite as common as it is in conversation at the time.

And she did that in South America, but she not only explained her experience, but I was able to see the transformation in her that seemed to have some durability over time. And that is when I started stepping back into researching psychedelics, looking at what had been published in the last, let's just call it 10 years as of that point in time.

And thinking about how I would approach it systematically with safeguards, with proper supervision, and basically approaching it the way I would have approached any of the topics in the 4-Hour Body. And that is what led me back into, along with a number of other interventions, I should say, so I wasn't betting the farm on psychedelics.

I also started TM at that point. I was-- - Excuse yourself. Some people might, Transcendental Meditation. These are like four to 10 day meditation retreats. - This was actually much shorter. It was a two or three day training. And you're visiting the instructor, I wanna say it's once or twice a day, probably once a day, and getting up to speed.

And I did this because I was going through a period of acute stress. This was finishing the 4-Hour Chef. This was actually probably in the years preceding that. And I had one friend who I'd seen really change from let's just call hyperkinetic high anxiety to low anxiety. And he said, "You have the time, you have the money, "pay for the course, just take it." Yes, there are all these criticisms of TM.

Yes, there are all these weird historical anecdotes of people trying to levitate and all this weirdness. Just ignore that. - Trying to levitate, nothing against that. If you actually levitate, then we gotta have a discussion. But trying to levitate seems like it. - Why not? - Every kid tries all sorts of things.

- Give it a go. He's like, "Just put that aside." Because I kept coming up with pushback. And he's like, "Look, all I'm saying is "it's like a warm bath for your mind "that you take twice a day "and it'll chill you the fuck out. "So try it." And I was like, "Okay, fine." - That's a good endorsement.

- I was like, at this point, I had been burning the candle at both ends so intensely. It's like, "Okay." So there was TM, and then I began examining how I might approach. Notice I didn't just jump into using them. I was like, "How could I approach taking psychedelics "in a logical sequence with proper protections, "with safety assurances?" And that took me probably a month or two.

And I was right in the middle of things. Northern California, you have access to a lot. And only then did I start looking at having my own experiences. And lo and behold, I mean, I'll cut to the chase, but the personal outcome, and there are many different benefits and risks I should make very clear.

These things can be extremely dangerous in certain ways. Generally, not physiologically, but they can be dangerous. I would say instead of three to four times per year on average, I probably have one depressive episode every two years. - That's a significant improvement. - Right. I mean, from a quality of life perspective, those are two different people.

And that then led me to, and as I did with all my workouts, right, I took copious notes over the span. I mean, now we're looking at 10 plus years. So if I were to ever write another book, it would probably be related to all of the really fine details of the experiments and my learnings, including some of the more bizarre things over the last 10 years.

But it would be just a beast to create. - With psychedelics, experiences with psychedelics. - Psychedelics and sort of psychedelic adjacent, non-ordinary experiences of consciousness, which I think often are touching at edges of the same thing, which is gonna be controversial for some folks. But to come back to the storyline, just to put a bow on that, when I saw the personal outcomes for me, the anecdata from friends who are facilitators who have worked with thousands of people, right, which is a pretty good sample size.

Still anecdote, but these are people who are very smart, who keep records. And I believe that these people have spotted patterns that are only going to be possible to test and verify over the next five to 10 years. So I, at least as a means of generating hypotheses, I take these people very seriously.

And then I started to connect with scientists whose work I had read, like Roland Griffiths at Johns Hopkins, began looking at the most compelling data related to say MDMA-assisted psychotherapy and complex PTSD. I made the commitment to myself that as soon as I had enough money to move the dial, 'cause I really felt like these tools were so outside of the normal paradigm of psychiatry and pharmacology.

And that made me very excited because it was uncrowded. There was very little funding coming into the space. It was high leverage. And I looked at it just as I've looked at my many startup investments. Limited downside risk, really high upside potential. And I should say before that, I'd already been funding in a very small way science.

So the first check I ever wrote was personally to Adam Ghazali's lab at UCSF. - Yeah, great lab. - Which at the time was looking at software. He's not gonna like this description, but I'm gonna simplify it. Software that might attenuate or reverse age-related cognitive impairment, specifically related to various aspects of attention.

And that was my first foray into funding early stage science, which was very analogous to me to funding early stage startups. And then later on, to touch on the reputational thing, I know this is a TED Talk, so thank you for listening. - No, this is great. Please, you're always so gracious on your podcast.

This is what people want. This is certainly what I wanna hear. - So on the reputational side, you're right that at the time, especially, let's just call it 2013 to 2015, this was not a comfortable national conversation of any type. - Yeah, I wouldn't have had this conversation back then.

- No way. - I don't know that I would have lost my job. It just would have raised a lot of eyebrows. Now such studies are happening at Stanford. - Yeah, the perception was that these are a professional third rail, at the very least, right? Also illegal, therefore, if I talk about them, am I giving someone probable cause?

Am I gonna get myself in some type of really tricky legal situation, et cetera? There are a lot of considerations. But I tested that, just like I was saying, I like to capture my assumptions on paper so I can stress this. And I was like, okay, I think that might be true.

Most people I know think that is true. But is it true? How could we test to see if that is true or not? And I decided to crowdfund for a Hopkins pilot study looking at psilocybin for treatment-resistant depression. And I thought to myself, okay, we have a couple of things falling in our favor here.

Number one, depression does not discriminate. So across socioeconomic classes, across gender, across race, this is a problem. Almost everyone knows someone who takes antidepressants who is still depressed. Okay, treatment-resistant depression, therefore, is the indication, psilocybin is the intervention. Let me crowdfund, and I did that throughout the time, CrowdRise, which was co-founded by Edward Norton, who had become a friend and was-- - The actor, Edward Norton.

- The actor, who's very smart, very, very, very smart. Also one of the best investors I've ever met, which a lot of people don't know. Very bright guy. And so crowdfunded, and I also like to put my money where my mouth is. I said, okay, guys, I'm gonna seed this.

I'm putting in X, the goal is to raise, I think it was 80,000, something like that, for the following study. And then I was like, let's see, let's see what happens. And there was basically zero negative blowback. And not only was there no discernible negative blowback, a number of people, and this was deliberate, I wanted to see this, a number of people came out of the woodwork to support in a bigger way.

And I was like, oh, okay, I see you. A handful of folks I knew, and I was like, oh, interesting. Okay, there are at least a half a dozen folks who are studying the same thing, who are paying attention to the same thing. And then I just got bolder.

I was like, okay, if I tested that, let me push, and then let's see what happens, and I'll wait. And lo and behold, I realized that the perception did not match the reality. The reality was, if you're talking about indications that cause an incredible amount of suffering for a very large number of people, even those who are anti-drug, per se, just say no to drugs, want solutions.

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