Bryan Johnson: I Just Took the Most Powerful Dose of DMT in the World... Here's What It Was Like

(0:00) David Friedberg intros Bryan Johnson (0:54) Why Bryan Johnson did 5-MeO-DMT (12:56) What brain scans actually show (18:36) Psychosis, bad trips, and life-altering decisions (26:23) The next frontier: organoids and gene therapy (33:26) GLP-1s, abundance, and human optimization (35:35) The longevity drug nobody's talking about? Thanks to our partner for making this happen! The Pod by Eight Sleep cools your bed to 55°F and uses Autopilot to optimize your sleep, all night. Use code ALLIN at https://www.eightsleep.com/allin for up to $350 off. Follow Bryan: https://x.com/bryan_johnson https://www.youtube.com/BryanJohnson Follow the besties: https://x.com/chamath https://x.com/Jason https://x.com/DavidSacks https://x.com/friedberg Follow on X: https://x.com/theallinpod Follow on Instagram: https://www.instagram.com/theallinpod Follow on TikTok: https://www.tiktok.com/@theallinpod Follow on LinkedIn: https://www.linkedin.com/company/allinpod Intro Music Credit: https://rb.gy/tppkzl https://x.com/yung_spielburg Intro Video Credit: https://x.com/TheZachEffect

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00David Friedberg?

  Brian Johnson, thanks for being here.

• 0:01Speaker 01

  Yeah, it's good to see you.

• 0:02David Friedberg?

  How are you feeling? Maybe just share with us what you did a few days ago.

• 0:05Speaker 01

  Yeah, I did a, I did five MEO DMT, which is the most powerful psychedelic on the planet. Somewhere between five and 10 times more powerful than DMT. And so, yeah, it's, so it's been 48 hours. I'm still learning how to talk about it.

• 0:29David Friedberg?

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• 0:54David Friedberg?

  Before we get into your experience, why did you choose to do it?

• 0:58Speaker 01

  Two things. One, mostly as a longevity experiment. So when we, when I started this project five years ago, the, the approach we had was go through all the scientific evidence ever published on health and longevity. Try to find the interventions that have the best evidence. And for effect size, and we just went down the list from top performing on down. So of course, you start with exercise, nutrition, you know, sleep. And you work your way down to things like hyperbaric oxygen therapy and sauna, and then rapamycin metformin. And so we never actually had on our radar psychedelics. They were always either an ancient medicine, you know, being used in ritualistic practices, or being pointed at things like depression and anxiety in certain trials.

• 1:42Speaker 01

  But it was never understood as a rejuvenation protocol, something that was for anti-aging. And so we found a preclinical evidence in mice on psilocybin. We thought, that's interesting. And so we did the world's most studied, the most quantified experiment doing psilocybin, three doses at 25mg of psilocybin.

• 2:00David Friedberg?

  Which are pretty high doses.

• 2:01Speaker 01

  Yeah, it's a clinical dose, a very, very close to a hero dose. And we found that we think it's a longevity therapy.

• 2:08David Friedberg?

  Let's get to that data in a minute. But then you decided to try five MEO this weekend.

• 2:13Speaker 01

  Yes.

• 2:14David Friedberg?

  Walk me through the experience, because you televised the whole thing. It was livestreamed. You looked amazingly calm going into it and going through the process. Walk us through your experience.

• 2:26Speaker 01

  Yeah, I think those who have done five MEO would probably relate with me that it feels like an impossible task to explain what it's like. So that caveat said, I'll give it a go. I'm stunned, absolutely floored, speechless. You, you basically experience raw consciousness and raw intelligence. It's this, so whatever, when I say these words, take these words that I commit to you, take that idea, multiply it by a thousand, and then move out infinite depth, infinite width, or width and depth, and then dimensions. And like, that gives you kind of like

• 3:08Speaker 01

  a rough map of like, the size and space that you deal with. And it was incredibly hard, because you, you get blasted into this space that is so foreign, you don't even know what's happening. It happens very quickly. Like, you inhale it. I did nine milligrams of intramuscular, and then seventeen, eighteen of it vaporized, and it hits you within ten seconds. You're just, you're out. And so, but what happens is you, you get in that space, and then Visual changes. Very, very little visual. Like, you see, on DMT, it's very visual, you'll meet the, you know, like the elves, or whatever else. This is not a visual experience. But you, you

• 3:51Speaker 01

  get in this world, and you lock in to basically, you either panic, because you feel like the gates of hell are going to open, that the, the stream of existence is just gonna just tear you to shreds, it's gonna shard you. And if you give up Like, break your brain. Yeah, if you feel like it's gonna like, threaten your sanity, like, is it gonna chop you up into little pieces? And so in that moment, you have to say, do I try to wrestle this, and I, I need to just like, wait it out until it's over, or you just relent, you say yes. And you have to, in that moment, you have to say yes, so thoroughly. You have to

• 4:32Speaker 01

  release all attachment, all preconditions, all want, all desire, you have to release self, ego, control, you just have to just relent entirely. And then when you do that,

• 4:46Speaker 01

  It opened up this unimaginable bliss and euphoria. And I, again, this is like a V1 of trying to explain this, but if I list out the, the most

• 5:01Speaker 01

  dynamic experiences I've had of a human, you know, uh, like certain accomplishments or getting married or having a child or overcoming a difficulty or like, you know, state your list of things. This is without question the most dynamic experience I've ever experienced as a human.

• 5:19David Friedberg?

  Does the internal chatter, the internal monologue of the ego turn off?

• 5:24Speaker 01

  Does.

• 5:24David Friedberg?

  So you can't hear yourself speaking? How do you rationalize what's going on if you don't have a dialogue going on?

• 5:30Speaker 01

  It's this visceral feeling, like you're, you're hyper aware of what's happening. It's not like you, you block out in the first like, we take a very high dose. You don't really know what's happening the first few minutes, but then you kind of come to and you're hyper aware of everything. It's not visual, but it's this, um,

• 5:50Speaker 01

  you're in the depths of existence, like this.

• 5:59Speaker 01

  It's just the most majestic

• 6:03Speaker 01

  experience achievable by a human, by, by intelligent life. I just can't imagine anything more miraculous.

• 6:11David Friedberg?

  You've studied the biology, the biochemistry, what goes on in the brain as this molecule hits your neurons?

• 6:18Speaker 01

  Yeah. So I mean, like it, um, I mean, one, it completely dissolves your default mode network.

• 6:25David Friedberg?

  Describe what that is.

• 6:26Speaker 01

  So like, um, it's, this is the engine that constructs self and ego. And so as you ruminate, you know, like you're going through.

• 6:35David Friedberg?

  Thinking through your day, what's next?

• 6:37Speaker 01

  Exactly.

• 6:37David Friedberg?

  How am I feeling?

• 6:38Speaker 01

  Yeah.

• 6:38David Friedberg?

  What should I be doing right now?

• 6:40Speaker 01

  Yeah.

• 6:40David Friedberg?

  Constant conversation.

• 6:41Speaker 01

  Yeah. Do I feel bad about myself? Do I feel, you know, like I, am I shy? Am I like, do I feel bad about whatever? Like you're doing this rumination stuff. Uh, kids don't have this rumination loop. Their, their default mode network is, is quiet. And as you age, you basically build up this default mode network into more stiffer patterns. And so as you age, your experience of reality becomes increasingly narrow. You have these big ruts that form. And so you can just see people and their patterns, like how open a child is to say like very random things. And as adults, you're just very, you're shut in. Like when I did psilocybin. One of the reasons why we did it is because it does have this effect where it dampens the default mode network. And we could pick this up with Kernel, the brain interface. You can see how the default mode network weakens. So basically, think of the brain

• 7:25Speaker 01

  like a globe with airports scattered about, and you have certain traffic patterns like New York to London. You have a certain number of flights every day. That's like a very strong connection. But New York to some small town in Arkansas has a very low traffic map. And so when you do something like psilocybin, it basically takes the airports, picks them up, and then repositions them in the world. So it's all scrambled. So the traffic patterns aren't the same. And then over time-

• 7:52David Friedberg?

  The neurons don't physically move, but the activity shifts around.

• 7:57Speaker 01

  Exactly.

• 7:57David Friedberg?

  Right? The neurons are a little bit more random than they normally would be, which arguably drives neuroplasticity, causes those neurons to reach out for new connections. And when new connections are made, new behaviors, new ways of thinking emerge-

• 8:11Speaker 01

  Exactly right.

• 8:11David Friedberg?

  -coming out of these therapeutics. Is that a fair way to describe it?

• 8:14Speaker 01

  Exactly right. So you look at my brain on psilocybin from Kernel, you see my patterns before, like the New York to London connection. You see my brain afterwards, and it's exactly what you said. New patterns are emergent. The old ones have quieted down. It's like a new map of connectivity. And so we saw that happen, and that does generate a lot of neuroplasticity.

• 8:32David Friedberg?

  And obviously, this neuroplasticity rewiring these connections in the brain is what allows trauma victims or folks that have a certain wiring that they keep repeating in their brain, which causes the trauma and the anxiety in their lives to get rewired. And then that trauma and that anxiety feels like it dissolves or melts away. Is that a fair-

• 8:51Speaker 01

  Exactly right.

• 8:52David Friedberg?

  Yeah.

• 8:53Speaker 01

  Yeah.

• 8:53David Friedberg?

  And so this has been documented in psilocybin. It's kind of well-understood. How did you connect that psilocybin data to an effort in longevity? Or was this just like a random idea? Let's try it out?

• 9:05Speaker 01

  Yeah. So we saw some mouse data that it had these effects. It also showed reduced inflammation. So we said, like, this is interesting, because most longevity therapies do something with inflammation, right? Like, inflammation is the killer. So if you can lower inflammation, a very good sign. You can do something that makes the brain more youthful and takes down those those big ruts. That's also useful. What we found at psilocybin, though, is that it had, we found a first in human observation. It had this this metabolic reset in the brain where my blood glucose before this was in the top ninety nine point five percentile of all the population.

• 9:42David Friedberg?

  Okay.

• 9:43Speaker 01

  After it went to the top ninety nine point nine percentile, like to move my blood glucose to that level is very, very hard. But basically, like, not like metformin where you're doing something on blood glucose. This just had a reset across the body, also changed my microbiome. Uh, so we saw full on effects. So then we said, okay, if that had that consequence, five M E O may have some similar characteristics.

• 10:04David Friedberg?

  And so no one had done this in five M E O before.

• 10:06Speaker 01

  Exactly. So there's like, there's, there's animal evidence. But it's the the similar dynamics of like, can you take the brain? And can you basically like smooth out the barnacles that accumulate? And five M E O D M T compared to psilocybin, like, just absolutely like blasted clean. My default mode network. It felt like psilocybin dampens it, like it softens it, but this thing just annihilated my default.

• 10:34David Friedberg?

  Turned it off completely. Yeah. It just, it just doesn't run the same way.

• 10:38Speaker 01

  Like, for an example, like, uh, this morning I woke up, uh, catching myself laughing in a dream. I have not laughed in a dream. I don't even know when I've ever laughed in a dream. But that is, after I woke up, I was like, that's really weird. Like, I don't remember laughing. I looked it up. Like, that is a characteristic of a child.

• 10:55David Friedberg?

  Right.

• 10:56Speaker 01

  And so you are restored to this childlike state. And I mean, the past couple of days, I have felt childlike, you know, yesterday morning, I felt that, you know, that emergent excitement, the bubbling of like, today's so exciting. I'm going to do new things. I'm going to have new experiences. Um, that you're just excited about all things. I haven't felt that. I don't even know when, you know, for so many years. So like, it really was, um, profound on every layer. And I see, and I'm stumbling too, because I didn't even talk about it yet.

• 11:27David Friedberg?

  During the day, you're hanging out, you're walking around. Is your brain having the same normal chatter that it did before? Or do you think that there's a persistent change in that default mode network?

• 11:38Speaker 01

  Yeah, definitely a change. Like, I was with my partner Kate yesterday and we, um, I did something that. Made her upset. And so like in that situation, you know, like when when couples are in that moment, you have like this negotiation, how do I sort this? And it all just became so clear to me, like when children have a fight, you have it out and it's just like done. Yeah. And you move on. But then adults take that and they like package it up and like they want to weaponize it be like, I got something on you. And I'm like move it. I'm going to move the chess pieces and like try to leverage this and and. Or they stored up like a snake in one of those things that pops out all the snakes later. Exactly. Package it all up.

• 12:19Speaker 01

  Exactly. And so like we had this and I I just felt absolutely like no need to escalate or to defend or to like, it was just easy. And it was a breakthrough in our relationship where I was able to communicate with her in a way. And so it's like laughing in my sleep. It's how I deal with my partner when I walk around. I just feel so much I I feel so much more funny, you know, like my ability to make quips that are just immediate. You know, like, so yeah, I just feel renewed as a person in a way that I just really didn't imagine. Have you tried hallucinogenics before you started your longevity path a couple of years ago? Yeah.

• 13:04Speaker 01

  And did you do that recreationally or therapeutically? It was mostly therapeutic in that. Yep. I I had sold my company, Branche of M O. I got a divorce. I left the Mormon church. And I was trying to remap like, what is life? Who am I? What do I do? So I was in that rebuilding stage where I just dabbled of like, you know, I did I did ketamine at Colonel. So when one of our first studies at Colonel is we said ketamine was a up and coming therapy for depression. And we posed the question, what happens when you do ketamine? And so we did the world's most extensive measurement of ketamine with Colonel before, during and after. And so that was interesting, like, and it had some kind of, you know, transient effect, but that's like a

• 13:44Speaker 01

  like a little league relative to. 5MEO.

• 13:47David Friedberg?

  And so as you've gone through this, maybe share a little bit of the MRI data that you're gathering and the other data mapping neurological effects.

• 13:54Speaker 01

  Yeah.

• 13:55David Friedberg?

  And tell us a little bit about what you've learned.

• 13:57Speaker 01

  So far, nothing. I have my subjective experience to share, but we have a structural brain MRI. We have a functional brain MRI. We did Kernel, which is like an optical interface. And then I did a real-time EEG capture.

• 14:10David Friedberg?

  And we should just talk about, I think it's important, structural, you can see the physical brain. Functional, you can see the activity in the brain. So neurons firing and neurons that are not firing.

• 14:22Speaker 01

  Yes.

• 14:22David Friedberg?

  Right?

• 14:22Speaker 01

  Yeah.

• 14:23David Friedberg?

  And then electrical actions that are measured by an electrical device.

• 14:27Speaker 01

  So we basically like wanted, because the brain is very, so we've had a lot of success rejuvenating my heart and my lungs and muscle and body fat. But rejuvenating the brain is very hard.

• 14:38David Friedberg?

  Right.

• 14:39Speaker 01

  And so we, this is why this is such a promising therapy. So we wanted to look at the brain through every modality possible. We wanted to look at blood flow, structural, molecular, you know, the wave pattern form. So it's a, it's a very high fidelity quantification. And so we'll see what the data comes out. I'm very excited. Yeah.

• 14:57David Friedberg?

  You did this on psilocybin as well, right?

• 14:58Speaker 01

  Yes.

• 14:58David Friedberg?

  You mapped the brain over time. What did you learn there?

• 15:01Speaker 01

  Dramatic restoration of youthful brain patterns.

• 15:06David Friedberg?

  Yeah, right.

• 15:06Speaker 01

  Yeah.

• 15:07David Friedberg?

  And what comes after 5MEO? I mean, how far do you take this?

• 15:14Speaker 01

  Yeah. Honestly, I am so encouraged by psychedelics. I, you know, again, in the community where I hang out, psychedelics have always been understood as, you know, it's like a retreat or it's like a ritual or you go to like do various explorations, but never in the world of longevity. It's never been understood as that thing. And now after seeing the data, now I am.

• 15:44Speaker 01

  And of course, you have to be very careful when talking about psychedelics because they're extremely powerful. It's not like go out and do them everybody, right? It's like it needs to be done properly with a licensed professional. It needs to be done carefully. The person needs to be in the right state. Like it is not to be taken lightly, but I am more interested than ever in psychedelic compounds. They're just uniquely powerful.

• 16:04David Friedberg?

  There's some arguments to be made that psychedelics can induce permanent psychosis, cause functional changes and drive some people that might be predisposed into schizophrenic states.

• 16:17Speaker 01

  That's right.

• 16:17David Friedberg?

  How did you get over those risks? Because for a lot of people, that would turn them off to trying psychedelics. And it's not a non-zero percentage of people that suffer these consequences.

• 16:28Speaker 01

  Yep, I agree. And also people who have really bad trips that leave them scarred. So it's, it really is. And I think in part of it is what could be contributing to this is people who, for example, who have tried magic mushrooms, you know, it's in a social situation. Someone's got a bag. You pull out some mushrooms. It's like, yeah, like ways blank. And they pop it in, but they have no idea what kind of mushroom strain they're eating. They don't know what the dose of psilocybin is. So it's like unquantified, unsupervised, wrong sentence setting. And so much of it, I think you can, the risk persists. But I don't think we've approached psychedelics with the appropriate rigor that we should to make it safe. And so it's not to say that we can solve for the safety issues for all

• 17:10Speaker 01

  people. Some people may not be the appropriate candidate for it. But I think if we do create a safety structure around it, they could deliver the benefits people want without, you know, with less of the risk. But definitely, I agree with you. Like it's, again, it deserves all the caution in the world.

• 17:27David Friedberg?

  Do you think it's like neurogenic, neuroplasticity, trauma resolution? I mean, what is the way that this is going to be allowed to become, call it a medical therapeutic that can be more broadly trialed and then eventually figure out how to bring it to people without it being, carrying all the risks and burdens that it does today?

• 17:46Speaker 01

  I mean, if I just subjectively compare my experience with 5MEO to having a better diet and exercising every day and sleeping well and doing the sauna and doing hyper red oxygen therapy. This was more efficacious than all of them in terms of the reset of me as a human. It just is incomparable. And I guess I'm really left pondering for this molecule to have such a gigantic impact. Now, like, how long will it last? What's the decay curve like? You know, will I find I I become the former Brian within 30 days, 60 days? I have to repeat this again? I don't know. But it really is, you know, when you sleep well, you feel great. You exercise, great.

• 18:30Speaker 01

  But like, nothing like what 5Mio did in terms of of like the reset of me as a human.

• 18:35David Friedberg?

  So let's just talk about the consequences outside of the physiological, which is life.

• 18:41Speaker 01

  Yeah.

• 18:42David Friedberg?

  There are lots of stories and friends that I have that and people that I know that have tried a heavy psychedelic, like an ayahuasca or something. They were the CEO of a company and then they quit their company and they go off to the jungle, leave their family, divorce their their partner. Makes such dramatic life changes because their perspective has been shifted so much that they reevaluate what matters in life to such a degree that they give up a lot of the things that mattered before.

• 19:11Speaker 01

  Yeah.

• 19:12David Friedberg?

  In the wake of that, there are people that feel they're a victim of that behavioral shift. The investors in the company, the employees, the family members, et cetera.

• 19:23Speaker 01

  Yeah.

• 19:24David Friedberg?

  Can you just talk a little bit about those broad risks? Because we've seen it and I don't know if you've seen the same. But friends that have kind of like said, I have this new perspective. I'm giving up my life.

• 19:34Speaker 01

  I've seen the same thing. And I, um, one investor told me that he even put it in the deal docs. That, you know, if we invest, you're not going to do these psychedelics. Because they wanted to minimize the the risk profile. It's a thing.

• 19:47David Friedberg?

  In your deal, in an investment in you?

• 19:48Speaker 01

  No, I just spoke because I've been doing this.

• 19:52Speaker 01

  People bring this up as a topic of conversation.

• 19:54David Friedberg?

  Right.

• 19:55Speaker 01

  And so they say like, I see you're doing this for longevity, but you know, like I've seen so many examples where people put money in, then you lose the founder. Like they're off.

• 20:04David Friedberg?

  They're gone.

• 20:05Speaker 01

  Everyone's high and dry. And so they were telling me that they put into DILTOX that they can't do this for the duration of the company. And so it is a thing and you know, I, I have nothing to say about it other than I know what happens. Um, also I would say that most people in the tech world that I'm familiar with, again, they've done this in retreat centers or in social environments. It's not quantified, it's not set in setting, it's, so it's a different thing. But I will say like, you know, I, I guess me as a person, what I'm trying to focus on, I came back even more motivated to do what I'm doing now. Uh, I don't have a desire to go off in the woods, you know, and like, and live that kind of life.

• 20:48Speaker 01

  It, it, it emboldened me to work on these things, but no question about it. You, you do have a dramatic shift in perspective and it's, it's very hard to get.

• 20:57David Friedberg?

  It begs a very important philosophical question. Who am I?

• 21:01Speaker 01

  Yes.

• 21:03David Friedberg?

  If I'm defined by my experiences, it roughly equates to my neurons are wired in a way.

• 21:12Speaker 01

  Yes.

• 21:13David Friedberg?

  That's a consequence of my experiences. And if I go in and take a drug and in a few hours rewire all my neurons, am I the same person?

• 21:21Speaker 01

  Yeah.

• 21:21David Friedberg?

  What makes Brian Brian? You can maybe recall some memories of Brian prior to taking the psychedelic, but Brian as a person has been rewired.

• 21:31Speaker 01

  Yes.

• 21:31David Friedberg?

  Are you a different person now? And what does that say about, are we ever a persistent person?

• 21:36Speaker 01

  Yeah.

• 21:37David Friedberg?

  Right?

• 21:37Speaker 01

  Yeah. Your question is spot on. Probably the most dramatic reconstruction of your 60 plus trillion cells than anything you can do in life. You know, like maybe like a near death experience, you know, would, would maybe be close, but it's a dramatic rewiring of you as a, as a human.

• 21:55David Friedberg?

  Your values can change too.

• 21:56Speaker 01

  That's right.

• 21:57David Friedberg?

  And you could judge the values pre and post, right? You could judge values ascribed to you by a religion, or perhaps values ascribed to you by responsibility to family members, children, spouses, partners, what have you. You abandon them after you go through this change. So your values have changed. Is it right or wrong?

• 22:16Speaker 01

  That's right.

• 22:17David Friedberg?

  I think it's another important question that comes out of all this.

• 22:19Speaker 01

  I agree. And like you now, like you now think about that. That's through the frame where the world changes at a certain speed. Now you take the world where it's changing faster. So we now know that it's hard to predict what's going to happen two weeks from now or a month, right? Like, things are changing very quickly. And so now you come up with this practical question. Can humans change fast enough in the world where AI is the dominant engine of innovation? And so in that case, you may want psychedelics as your ally to say, as a human, I'm struggling to move with the change.

• 22:54David Friedberg?

  Yeah.

• 22:55Speaker 01

  And so there's potentially where it flips from a liability to an asset where now I do want that restructure changing, even though you have some tail risk of like, maybe my priorities will shift.

• 23:06David Friedberg?

  I think you have profound, what I would call psycho flexibility. And I think most people don't. They have either a disinterest in changing who they are overnight or they're fearful of the ramifications or the experience and that they wouldn't go through it. How far would you take it? Would you wire yourself up to a Neuralink or neural enhancement device that would give you the ability to have information on demand and maybe change your personality and capacity as a human through an implant? Would you consider doing something like that? You would? Would you consider a transgenic system where you basically take a plasmid, which would then express a set of proteins in your body and change gene expression profiles and cells in your body and basically could rewire you as a different person?

• 23:51Speaker 01

  Yes.

• 23:51David Friedberg?

  Yes. Is there a limit to what you would try?

• 23:53Speaker 01

  No.

• 23:53David Friedberg?

  Interesting. Where do you think that comes from?

• 23:55Speaker 01

  I think I find it to be the most exciting configuration of life. The ability to play on the frontier. Novelty and expedition and challenge.

• 24:08Speaker 01

  That's really my.

• 24:09David Friedberg?

  Did you always have it or are you responding to childhood suppression of those?

• 24:15Speaker 01

  It's probably it's probably an overcompensation of of trauma response like most things are. And so, you know, as a child, I lived in a very structured religious environment where things were cemented. Like, here's the story, here's the plan, here's what you do and what you don't do.

• 24:28David Friedberg?

  Yeah.

• 24:29Speaker 01

  And so, yeah, maybe it's probably just I'm now flipped in the opposite.

• 24:33David Friedberg?

  Yeah.

• 24:33Speaker 01

  And so, I mean, that's probably true that I really, I don't trust my internal generation of reality.

• 24:40David Friedberg?

  Yeah.

• 24:40Speaker 01

  You know, I know I'm always making things up. I've got one hundred and eighty eight chronicle biases like all humans do. So I'm just, I'm generally suspicious of all things all time and I don't take myself very seriously. So I just find the frontier play space to be like, right now, I mean, you know, what you're doing in building companies? Like, you just open up a toolkit and say, like, what can I build? And how do I modify? And so I agree with you, I do have a strong proclivity towards openness play.

• 25:06David Friedberg?

  Do you find that you've been challenged in maintaining, I would call it, external responsibility? As you explore and enhance yourself so much? Do you give up the responsibility to others around you who maybe are dependent on you or in need of you?

• 25:19Speaker 01

  Yeah, I have three kids. And so I do think about them a lot. And I, being a father is a really important thing to me and it's an important part of my identity. And so that has not changed. So I've never vacillated on that or changed my disposition towards that. For those around me, I guess fortunately I have a a social group that just says, go and play. There's, there's really no one in my life that tries to claw me back. There's no Velcro.

• 25:47David Friedberg?

  Yeah.

• 25:48Speaker 01

  It's just all encouraging. And so that, I guess I feel very fortunate that everyone around me, and they're willing to take the risks. I mean, this is, when I sat down for five MEO, I mean, my partner Kate, like, she's got. A ton of risk. Like, what if it goes poorly? What if I change my perspectives? What if something bad happens? So.

• 26:05David Friedberg?

  Well, one could make an argument that taking that degree of risk where something could have gone wrong, the people around you are enabling versus being supportive, right?

• 26:13Speaker 01

  That's right. That's right.

• 26:14David Friedberg?

  I mean, that's a consequence, but let's shift topics to other

• 26:20David Friedberg?

  modalities for longevity.

• 26:22Speaker 01

  Yeah.

• 26:23David Friedberg?

  What else is on the horizon? So you've had this profound set of experiences with psychedelics. You've documented in a very extraordinary and exquisite fashion, all of the other things that you've been doing. The interventions, are there other things that are on the horizon that you're either excited about or that you're considering yourself?

• 26:39Speaker 01

  Yeah, I mean, two of the ones that we've spoken about, cell therapy and gene therapy.

• 26:42David Friedberg?

  Yeah.

• 26:43Speaker 01

  Yeah, they they're all in the pipeline, so they're not ready yet. We've we've knocked out all the stuff you can do today. Like, we've gone through it all, done it all. The next gen therapies are just not there yet. So we're looking at mitochondrial rejuvenation.

• 26:57David Friedberg?

  I think that's incredible. I think mitochondrial augmentation therapy. And there was a paper I saw where in order to get the mitochondria in the cell, they coated the mitochondria in effectively a red blood cell envelope, which made it more transportable into cells and less attacked by the immune system.

• 27:13Speaker 01

  Exactly.

• 27:13David Friedberg?

  Which is incredible. And I'm a big, big, big believer in this this this course of therapy. I mean, this is going to be a whole therapeutic modality that no one has even recognized.

• 27:22Speaker 01

  I agree. We have our first mitochondrial therapy lined up, so.

• 27:25David Friedberg?

  How are you going to do it? You're like 99.9%. You need someone who's like 48.7% to try the mitochondrial.

• 27:32Speaker 01

  I agree with you.

• 27:33David Friedberg?

  Particularly like, you know, I think they tried it in Parkinson's patients, Alzheimer's patients. That's where you could really see profound shifts in in certain metrics. For you, it's like 99.9% to what?

• 27:43Speaker 01

  Like, yeah, I have the mitochondria, you know, of a 48-year-old, right? So like, what if I?

• 27:48David Friedberg?

  That's right.

• 27:49Speaker 01

  What if I could? Yes.

• 27:50David Friedberg?

  You could go to your sibling's child because the mitochondria is passed maternally.

• 27:55Speaker 01

  Yeah.

• 27:56David Friedberg?

  Because it's in the egg cell.

• 27:57Speaker 01

  Yeah.

• 27:57David Friedberg?

  So it's the mother's mitochondria. So if you go down the mother's line maternally, if you have a sister who has a kid, they're going to have very young mitochondria. You can take a little blood sample and then grow their mitochondria extensively and use that as a biological match to you.

• 28:12Speaker 01

  This is a perfect extension. I've had a blood boy as a son.

• 28:15David Friedberg?

  Yeah.

• 28:16Speaker 01

  So now I'm just going to go to the extended family and be like, guys, it's a family project.

• 28:21David Friedberg?

  Yeah, family project.

• 28:21Speaker 01

  Yeah, exactly.

• 28:22David Friedberg?

  Yeah. Well, that one's super interesting.

• 28:24Speaker 01

  We also have one that we're doing. I'm now building.

• 28:27David Friedberg?

  Sorry, are you going to do your own mitochondrial transplantation? You're going to build a bioreactor or are you working with one of the third parties?

• 28:32Speaker 01

  Yeah, a third company. Yeah, so I'll do a blood draw in the next week or two. They'll spin up.

• 28:37David Friedberg?

  They'll do it?

• 28:37Speaker 01

  Yeah.

• 28:38David Friedberg?

  Okay.

• 28:38Speaker 01

  Yep.

• 28:39David Friedberg?

  So you're going to get your mitochondria, which have some, you know, the problem with mitochondria, as you know, is mitochondrial DNA degradation over time, right? It accelerates for certain people, but that way, if you go back to a young person, you have young mitochondria.

• 28:52Speaker 01

  Exactly right.

• 28:53David Friedberg?

  Then you're going to multiply yours out.

• 28:54Speaker 01

  Yes.

• 28:55David Friedberg?

  And probably select a little bit or healthier ones?

• 28:57Speaker 01

  Exactly right.

• 28:58David Friedberg?

  Right, okay. And then put it back in.

• 28:59Speaker 01

  It's very explorative. We don't know. We're one of the first. They're in phase two now.

• 29:04David Friedberg?

  Do you sprint?

• 29:05Speaker 01

  Yeah, I do.

• 29:06David Friedberg?

  So you could probably score if you did it intramuscular, like mitochondrial there. You could sprint and see your score.

• 29:11Speaker 01

  That's a great idea.

• 29:12David Friedberg?

  Yeah, thank you.

• 29:13Speaker 01

  Yeah.

• 29:13David Friedberg?

  That would be a great way to measure it rather than just a basic biomarker perspective. Be really interesting to see.

• 29:20Speaker 01

  Yeah. Sprinting is one of the most underappreciated longevity therapies.

• 29:23David Friedberg?

  Yeah, I don't do it.

• 29:25Speaker 01

  Oh, man.

• 29:25David Friedberg?

  I've got the age of a 74-year-old, roughly.

• 29:29Speaker 01

  Is that right?

• 29:32David Friedberg?

  I'm definitely not keeping track with you. Would you consider, or have you looked at any plasmids where you take a gene as DNA, put it in your body, and then that gene makes a protein in your body that does something?

• 29:44Speaker 01

  Like the one we were looking at in the Foxal3 expression? Yeah, exactly. So the mesocellular stem cells packaged up with the Foxal3 delivery, that showed that over 50% of tissues getting that rejuvenation.

• 29:54David Friedberg?

  It's unbelievable.

• 29:55Speaker 01

  It's like the.

• 29:55David Friedberg?

  Unbelievable.

• 29:56Speaker 01

  It's the best demonstration in the entire world.

• 29:58David Friedberg?

  That's perfect for tissue regeneration, like as a particular application set, tissue regeneration, using that sort of system.

• 30:03Speaker 01

  Seems like a no brainer.

• 30:04David Friedberg?

  It's like, yeah.

• 30:05Speaker 01

  It's safe, right? Yes, I reached out to that Chinese professor. I'm really interested in seeing it replicating. I would love.

• 30:12David Friedberg?

  You reached out to the Chinese professor?

• 30:14Speaker 01

  Yeah.

• 30:14David Friedberg?

  That's awesome. We sent that paper.

• 30:16Speaker 01

  Yeah, yeah, exactly.

• 30:17David Friedberg?

  Yeah, that's awesome.

• 30:18Speaker 01

  So.

• 30:19David Friedberg?

  Did he respond?

• 30:19Speaker 01

  Uh, yeah.

• 30:20David Friedberg?

  Awesome.

• 30:20Speaker 01

  Yeah.

• 30:21David Friedberg?

  Good.

• 30:22Speaker 01

  So we, I'd love to do that. I'd love to actually build it ourselves.

• 30:26David Friedberg?

  Yeah.

• 30:26Speaker 01

  But that's like a two year project, so.

• 30:29David Friedberg?

  AI can help make it faster.

• 30:30Speaker 01

  That's true.

• 30:31David Friedberg?

  Yeah.

• 30:31Speaker 01

  Actually, that's true.

• 30:31David Friedberg?

  AI as a project manager for these sorts of programs is.

• 30:34Speaker 01

  You know, that's true. We, we spoke about this six months ago.

• 30:37David Friedberg?

  Yeah. And things are so different.

• 30:38Speaker 01

  So different now, six months later, and in terms of stand that up. So that was cool. So I think that's a good, good option. But also I'm doing Brian Johnson organoids. So we took my IPSEs. We now have them.

• 30:49David Friedberg?

  Infused pluripotent stem cells.

• 30:50Speaker 01

  Exactly.

• 30:51David Friedberg?

  So you took your cells, turn them into stem cells.

• 30:53Speaker 01

  Yep.

• 30:53David Friedberg?

  Yeah.

• 30:53Speaker 01

  So now we're doing in dish. So now we have like a Brian Johnson heart, liver, lungs. And now we're going to try molecules on me and in.

• 31:00David Friedberg?

  So you have a plot. So, so let me just walk the audience through this. So you take cells off of your skin or something.

• 31:04Speaker 01

  Blood.

• 31:05David Friedberg?

  Blood. And then you put these yamanaka factor proteins on those cells. Causes those cells to become stem cells, which means they can then turn into any other cell.

• 31:12Speaker 01

  Yeah.

• 31:12David Friedberg?

  And then you put other proteins on them to turn them into a heart cell or a eye cell or what have you. And now you've got a store of these tissue specific Brian Johnson cells.

• 31:23Speaker 01

  Yes.

• 31:23David Friedberg?

  That you then use for.

• 31:25Speaker 01

  Like you can say, okay, what if you get Brian Johnson blank, you know, drug? What is, what happens? Is it good? Is it bad? What are the side effects?

• 31:33David Friedberg?

  In the PT dish, you put the drug in there.

• 31:35Speaker 01

  Exactly.

• 31:35David Friedberg?

  See what happens.

• 31:35Speaker 01

  Yeah.

• 31:36David Friedberg?

  Okay.

• 31:36Speaker 01

  So you're like, you can simulate all these experiments. So now you, you get the advantage of time, of acceleration of like what to take, why, what dose.

• 31:43David Friedberg?

  That's awesome.

• 31:44Speaker 01

  What combinatorial things to consider.

• 31:45David Friedberg?

  Yeah.

• 31:46Speaker 01

  And so we, we have the organoids stood up. We haven't done our first takes yet.

• 31:48David Friedberg?

  Yeah.

• 31:49Speaker 01

  So that's interesting because now I have to do this old school methodology, like put it in my body, wait to see what happens. Is it good? Is it bad? What, you know, how does it affect everything else?

• 31:58David Friedberg?

  Yeah, totally.

• 31:59Speaker 01

  That's a good one. But I mean, I don't know. We'll see. It's cool in concept. I mean, TBD if it actually works, so we'll see.

• 32:05David Friedberg?

  Have you tracked any of the alternatives to Yamanaka factors, the factor discovery work that's going on? And do you think there's anything worth testing at this stage?

• 32:13Speaker 01

  Yeah, I'm an investor in New Limit, so I've talked to them about where they're at.

• 32:17David Friedberg?

  Blake and Brian's company.

• 32:19Speaker 01

  They've done, I mean, they've made remarkable progress.

• 32:22David Friedberg?

  Yeah.

• 32:23Speaker 01

  They figured out how to computationally solve the discovery process.

• 32:27David Friedberg?

  Yeah.

• 32:27Speaker 01

  And so they're much faster than they initially thought, and so that's very encouraging.

• 32:31David Friedberg?

  You know, the big challenge with Yamanaka factors is always dosing. If you overdose a cell, a one cell, that cell can become a cancer cell and take off as a tumor.

• 32:41Speaker 01

  Yeah.

• 32:41David Friedberg?

  So the sensitivity that you need to have to get the right number of the factors, which is a protein into the cell, needs to be perfectly tuned.

• 32:49Speaker 01

  Yep.

• 32:49David Friedberg?

  So I have a theory that this will end up being solved by cellular switches. That will end up putting machinery into the cells that can turn on or off the protein synthesis at the right dosing, based on the measurement of gene expression in the cell.

• 33:03Speaker 01

  Yeah.

• 33:04David Friedberg?

  That's my theory on where this will end up.

• 33:06Speaker 01

  That makes a lot of sense. Any other control mechanism will be inadequate.

• 33:09David Friedberg?

  That's right.

• 33:09Speaker 01

  The feedback loop just...

• 33:10David Friedberg?

  All you need is one error and you're trouble.

• 33:12Speaker 01

  Yeah.

• 33:13David Friedberg?

  But it is, it is the most profound, I think, technology that humanity is dealing with today besides AI. We're not quite there with fusion, which I would argue is probably a distant third, but it is very powerful.

• 33:22Speaker 01

  I agree.

• 33:22David Friedberg?

  What's possible.

• 33:23Speaker 01

  And in the future, like, I think we'll look back and we'll see GLP-1s as the first big drop.

• 33:28David Friedberg?

  Yeah.

• 33:28Speaker 01

  Of like, what, I can just inject myself and like it solves hunger and...

• 33:31David Friedberg?

  Totally.

• 33:31Speaker 01

  Yeah, and then the second will probably be something like New Limit or one of these fox, one of these plasma-based FoxO3 therapies where it will show real life, like dramatic changes.

• 33:41David Friedberg?

  Totally.

• 33:42Speaker 01

  And then humanity will shift as like longevity being a vision of sci-fi, you know, rich people pursuit to like something that is truly, I mean, go back to like the conversation on, on the temptation towards socialism. Right? Like if you can feel robust in your ability to pursue life and be healthy and vibrant and in control, I think these things would have dramatic changes to society, not just in health, but like...

• 34:09David Friedberg?

  Well, any form of abundance, whether it's abundance in food, in energy, in housing, in mobility, in lifespan. The more abundance people get, the happier they are.

• 34:17Speaker 01

  Yes.

• 34:18David Friedberg?

  And the more you're improving abundance in the world, the better we are going to live as a group of people together on planet Earth.

• 34:25Speaker 01

  Exactly.

• 34:25David Friedberg?

  The happier we will all be with each other.

• 34:27Speaker 01

  I think honestly, like a lot of the.

• 34:29David Friedberg?

  External conflict only comes from internal unhappiness.

• 34:32Speaker 01

  Hundred percent. So if you look at the general malaise of like American society, like no wonder uh things are shitty, right? Like you've got 84% of people have metabolic disorder. More than 40% of people are obese. Like we're just in really poor health. Nobody's sleeping. Everyone's on their phone. We have mental health issues. Like no wonder you have the proclivity towards these kinds of outcomes. Like so if you could get the health in check, it changes the psychological disposition of you, your community, your country. Like you have much more of a can do attitude. Like I can take on the world and I can do hard things. But when you're not feeling well, like it's just, everything is just so much harder.

• 35:06David Friedberg?

  Yeah, 100%. And so in light of all of these new therapeutic modalities and these new opportunities that seem to be biologically proven and have these profound effects, why continue to tinker with psychedelics? Like are they as profound or are they a compliment? Or like, how do you think about fitting all of this portfolio of things that you're looking at together?

• 35:24Speaker 01

  Yeah. I mean, I guess the question is, um, I forget on the Foxhole 3 study. I don't know if they saw brain rejuvenation.

• 35:29David Friedberg?

  Didn't see that. I did not see that. And I don't, I don't remember. I mean, it is a very complicated organ.

• 35:35Speaker 01

  Yeah, exactly.

• 35:36David Friedberg?

  It's insane.

• 35:37Speaker 01

  It's very hard to reach.

• 35:38David Friedberg?

  You know, you can grow muscle tissue back and you can grow skin tissue back. And it's kind of like, okay, I grew a little X. Like if you grow the neurons back, maybe in the wrong way, like we don't know.

• 35:49Speaker 01

  Yeah.

• 35:50David Friedberg?

  Because it's never been done before.

• 35:51Speaker 01

  Yeah.

• 35:52David Friedberg?

  So understanding the consequence of neuro regeneration is like.

• 35:57Speaker 01

  So I wonder like if the role in my play, like, you know, maybe psilocybin and 5-MEO won't be um, you know, meaningful for like basic functions of the body. But maybe it's the uh, the outperformer in usefulness of your, of your disposition towards reality. Like one thing I'm apprehensive about is I'm 48. And so as you start climbing to your 50s, 60s, you do really narrow. Like your ambition goes from I can do anything to start, you know, narrowing down further and further and. I worry about using, losing a youthful disposition of a can do attitude of anything is possible.

• 36:40David Friedberg?

  Totally.

• 36:40Speaker 01

  And maybe that's the role psychedelics is you just get awash of like the snap back of like, I can and I can bounce.

• 36:48David Friedberg?

  Yeah.

• 36:48Speaker 01

  That definitely been the case for me. So I think they do probably play a really important role of like, they're probably a set of things that for certain people that will, um,

• 36:59Speaker 01

  basically like, I mean, I felt like it was like thirty, forty years of

• 37:06Speaker 01

  psychological rejuvenation. Like, you know, it's like to transport me back to a childlike state.

• 37:10David Friedberg?

  Yeah.

• 37:10Speaker 01

  That is insane. I don't get that from the sauna.

• 37:12David Friedberg?

  Yeah.

• 37:13Speaker 01

  Or from eating well, or from sleeping well. Like, I'm still.

• 37:15David Friedberg?

  Right.

• 37:16Speaker 01

  So it's just unique.

• 37:18David Friedberg?

  Yeah, amazing. Well, listen, I'm gonna go drink alcohol and eat carbs and stay out late. I don't know. What are you gonna do?

• 37:24Speaker 01

  Yeah, I'm gonna go to bed on time. Yeah.

• 37:26David Friedberg?

  Okay.

• 37:27Speaker 01

  Do my wind down routine.

• 37:28David Friedberg?

  Yeah, you do you.

• 37:29Speaker 01

  Yeah.

• 37:29David Friedberg?

  But.

• 37:29Speaker 01

  You as well. Enjoy it.

• 37:31David Friedberg?

  Yeah. I appreciate it. This has been great. Brian Johnson. Thank you.

• 37:34Speaker 01

  Thanks.

• 37:34David Friedberg?

  Yeah, that was awesome.

• 37:35Speaker 01

  That was great.