Brian Johnson, thanks for being here.
Yeah, it's good to see you.
How are you feeling? Maybe just share with us what you did a few days ago.
Yeah, I did 5-MeO-DMT, which is the most powerful psychedelic on the planet. It's somewhere between five and 10 times more powerful than DMT. And so, yeah, it's been 48 hours. I'm still learning how to talk about it.
You know what many of the biggest tech CEOs and VCs have in common? They sleep on the Pod by Eight Sleep. It's become tech's favorite way to sleep, and for good reason. A cover that goes on any mattress, cools it down to 55 degrees, and uses AI to adjust your temperature all night. Up to 34% more deep sleep. No wearable needed. Go to eight.com/allin and use code all-in for up to $350 off your pod purchase today.
Before we get into your experience, why did you choose to do it?
Two things. One, mostly as a longevity experiment. So when I started this project five years ago, 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 for effect size, and we just went down the list from top performing on down. So, of course, you start with exercise, nutrition, 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 being used in ritualistic practices or being pointed at things like depression and anxiety in certain trials, but it was never understood as a rejuvenation protocol, something that was for anti-aging. And so we found pre-clinical 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 25 milligrams of psilocybin.
Which are pretty high doses.
It's a clinical dose, very close to a hero dose, and we found that we think it's a longevity therapy.
Let's get to that data in a minute. But then you decided to try 5-MeO this weekend. Walk me through the experience because you televised the whole thing. It was live streamed. You looked amazingly calm going into it and going through the process. Walk us through your experience.
Yeah, I think those who have done 5-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 basically experience raw consciousness and raw intelligence. So whatever when I say these words, take these words that I committed to you, take that idea, multiply it by a thousand, and then move out infinite depth, infinite width, and then dimensions. And that gives you kind of like a rough map of like the size and space that you deal with. And it was incredibly hard because you get blasted into this space that is so foreign you don't even know what's happening.
Like you inhale it. I did 9 milligrams of intramuscular and then 18 of vaporized, and it hits you within 10 seconds. You're out. And so, but what happens is you get in that space and then...
Very little visual. Like you see on DMT, it's a very visual, you'll meet the elves or whatever else. This is not a visual experience, but you 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 stream of existence is just going to tear you to shreds. It's going to shard you. And if you give up, like break your brain. Yeah. You feel like it's going to threaten your sanity. Like is it going to chop you up into little pieces? And so in that moment, you have to say, do I try to wrestle this and I need to just wait it out until it's over, or you just relent and you say yes. And you have to in that moment, you have to say yes so thoroughly. You have to release all attachment, all preconditions, all want, all desire. You have to release self, ego, control. You just have to relent entirely. And then when you do that, it opened up this unimaginable bliss and euphoria. And again, this is like a V1 of trying to explain this, but if I list out the most dynamic experiences I've had as a human, you know, like certain accomplishments or getting married or having a child or overcoming a difficulty, or you know, state your list of things. This is without question the most dynamic experience I've ever experienced as a human.
Does the internal chatter, the internal monologue of the ego turn off?
So you can't hear yourself speaking, how do you rationalize what's going on if you don't have a dialogue going on?
It's this visceral feeling like you're hyper aware of what's happening. It's not like you block out in the first, like when you 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, you're in the depths of existence like this. It's just the most majestic experience achievable by intelligent life. I just can't imagine anything more miraculous.
You've studied the biology, the biochemistry. What goes on in the brain as this molecule hits your neurons?
Yeah. I mean, one, it completely dissolves your default mode network.
So it's the engine that constructs self and ego. And so as you ruminate, you know, like you're going through thinking through your day, what's next? How am I feeling? What should I be doing right now? Constant conversation. Do I feel bad about myself? Am I shy? Do I feel bad about whatever? Like you're doing this rumination stuff. Kids don't have this rumination loop. Their default mode network 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 in their patterns, like how open a child is to say very random things. And as adults, you're just very 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 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 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 around the world. So it's just all scrambled so that the traffic patterns aren't the same, and then over time, the neurons don't physically move, but the activity shifts around.
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 coming out of these therapeutics. Is that a fair way to describe it?
Exactly right. So you look at my brain on psilocybin from Kernel, you see my patterns before like the New York-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.
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?
Yeah. 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.
Yeah, it was. 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? Inflammation is the killer. So if you can lower inflammation, a very good sign. If you can do something that makes the brain more youthful and takes down those big ruts, that's also useful. What we found with psilocybin though is we found a first-in-human observation, it had this metabolic reset in the brain where my blood glucose before this was in the top 99.5 percentile of all the population. After, it went to the top 99.9 percentile. To move my blood glucose from that level is very, very hard. But it basically, not like metformin where you're doing something on blood glucose, this just had a reset across the body, also changed my microbiome. So we saw a full-on effect. So then we said okay, if that had that consequence, 5-MeO may have some similar characteristics.
No one had done this in 5-MeO before.
Exactly. So there's some animal evidence, but it's the similar dynamics of like can you take the brain and can you basically smooth out the barnacles that accumulate? And 5-MeO-DMT compared to psilocybin, like just absolutely blasted clean my default mode network. It felt like psilocybin dampens it, like it softens it, but this thing just annihilated my default mode network.
Turned it off completely.
Yeah, it just doesn't run the same way. And like for an example, this morning I woke up 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 and like that is a characteristic of a child. And so you are restored to this childlike state. And I mean the past couple days I have felt childlike. You know, yesterday morning I felt that emergent excitement, the bubbling of like today is so exciting. I'm going to do new things. I'm going to have new experiences. That you're just excited about all things. I haven't felt that. I don't even know when, for so many years. So like it really was profound on every layer. And I see I'm stumbling through this because I don't even know how to talk about it yet.
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?
Yeah, definitely a change. Like I was with my partner Kate yesterday and I did something that made her upset. And so like in that situation, you know, like 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. 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, right? I'm going to move the chess pieces and like try to leverage this. Or they store it up like a snake in one of those things that pops out all the snakes later, you know? It's like package it all up. Exactly. And so like we had this and I just felt absolutely like no need to escalate or to defend, 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 more funny, you know, like my ability to make quips that are just immediate. 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?
And did you do that recreationally or therapeutically?
It was mostly therapeutic in that I had sold my company Braintree. 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. Like I did ketamine at Kernel. So one of our first studies at Kernel is we said ketamine was an 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 Kernel before, during, and after. And so that was interesting, it has some kind of transient effect, but that's like a little league relative to 5-MeO.
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. And tell us a little bit about what you've learned 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 real-time EEG capture.
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, right? And then electrical actions that are measured by an electrical device.
So we basically, I 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. And so 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, the wave pattern form. So it's a very high fidelity quantification. And so we'll see what the data comes out. I'm very excited, yeah.
You did this on psilocybin as well, right? You mapped the brain over time. What did you learn there?
Dramatic restoration of youthful brain patterns.
Yeah. Right. And what comes after 5-MeO? I mean how far do you take this?
Yeah. Honestly, I am so encouraged by psychedelics. You know, like 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 do various explorations, but never in the world of longevity. It's never been understood as that thing. And now after seeing the data, 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 needs to be done properly with a licensed professional. It needs to be done carefully. The person needs to be in the right state. It is not to be taken lightly. But I am more interested than ever in psychedelic compounds. They're just uniquely powerful.
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. That's right. 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 nonzero percentage of people that suffer these consequences.
Yep. I agree. And also people who have really bad trips that leave them scarred. So 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 weighs 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 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 people. Some people just 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 with less of the risk. But definitely I agree with you, it deserves all the caution in the world.
Do you think it's like neurogenic, neuroplasticity, trauma resolution? And 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 carrying all the risks and burdens that it does today.
I mean if I just subjectively compare my experience with 5-MeO to you having a better diet and exercising every day and sleeping well and doing the sauna and doing hyper 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 like for this molecule to have such a gigantic impact now, like how long will it last? What's the decay curve like? Will I find I become the former Brian within 30 days, 60 days? Do I have to repeat this again? I don't know. But it really is, you know, when you sleep well, you feel great. When you exercise, great. But like nothing like what 5-MeO did in terms of the reset of me as a human.
So let's just talk about the consequences outside of the physiological, which is life. There are lots of stories and friends that I have 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 partner. Make such dramatic life changes because their perspective has been shifted so much that they re-evaluate what matters in life to such a degree that they give up a lot of the things that mattered before. 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, etc. 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.
I've seen the same thing and 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 risk profile. It's a thing.
In your deal, in an investment in you.
No, I just spoke because I've been doing this, people bring this up as a topic of conversation, right? 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, everyone's high and dry. And so they were telling me that they put into deal docs that they can't do this for the duration of the company. And so it is a thing. And you know, I have nothing to say about it other than I know it happens. 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 and setting. So it's a different thing. But I will say like, 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. I don't have a desire to go off in the woods, you know, and live that kind of life. It emboldened me to work on these things, but no question about it. You do have a dramatic shift in perspective, and it's very hard to get.
It begs a very important philosophical question. Who am I? If I'm defined by my experiences, it roughly equates to my neurons are wired in a way. 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? 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. Are you a different person now? And what does that say about are we ever a persistent person?
Right. Yeah, your question is spot on. Probably the most dramatic reconstruction of your 60 plus trillion cells than anything you can do in life. Yeah. Like maybe like a near-death experience would maybe be close, but it's a dramatic rewiring of you as a human.
Your values can change, too.
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? I think is another important question that comes out of all this.
I agree. And like you now think about that, that's been 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? 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, like you may want psychedelics as your ally to say, as a human, I'm struggling to move with the change.
Yeah. And so there's potentially where it flips from a liability to an asset where like now I do want that restructure changing even though you have some tail risk of like maybe my priorities will shift. I think you have profound what I would call psychoflexibility 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 neural link 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? 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 can rewire you as a different person?
Yes. Is there a limit to what you would try?
Oh, interesting. Where do you think that comes from?
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. That's really my...
Did you always have it or are you responding to childhood suppression of those?
It's probably an overcompensation 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.
And so, yeah, maybe it's probably just I'm now a flip in the opposite. And so, I mean, that's like probably true that I really don't trust my internal generation of reality. You know, I know I'm always making things up. I've got 188 cognitive biases like all humans do. So I'm just 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 a company is like you just open up a toolkit and say like what can I build and how do I modify. So I agree with you, I do have a strong proclivity towards openness of play.
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?
Yeah, I have three kids and so I do think about them a lot and 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 social group that just says go and play. There's really no one in my life that tries to claw me back. There's no Velcro. It's just all encouraging. And so 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 5-MeO. I mean, my partner Kate, she's got a ton of risk. Like what if it goes poorly? What if I change my perspectives? What if something bad happens?
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?
That's right. That's right.
I mean, yeah, that's right. That's a consequence. But let's shift topics to other modalities for longevity. 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 with interventions. Are there other things that are on the horizon that you're either excited about or that you're considering yourself?
Yeah. I mean, two of the ones that we've spoken about, cell therapy and gene therapy. They're all in the pipeline. So, they're not ready yet. 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. 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 which is incredible. And I'm a big, big, big believer in this course of therapeutic modality that no one has even recognized.
I agree. We have our first mitochondrial therapy lined up. So how are you going to do it? You're like 99.9%. You need someone who's like 48.7% to try the mitochondrial.
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 certain metrics. For you it's like 99.9 to what?
Yeah, I have the mitochondria of a 48-year-old, right? So like what if I...
