Ketamine & Cocaine: Ranking Drugs for Longevity (Part 1)

What happens to the brain when you take ketamine? Think of it like planet Earth with airports. And when you do ketamine, it's like you just pick up all the airports in the world and you scramble them. Before I did ketamine, and I guess I did this actually unknowingly in the office, we're walking to another room for a different meeting, and there was a big wall in between. And instead of walking around the office to get around it, I thought, why don't I just jump over the wall? That makes much more sense. And so I just jumped over the wall and I didn think about it, and my co workers were like, brian, what are you doing? That is really odd. And I thought, oh, you're right. I guess that might be a little odd. I was open to different ideas and I wasn't as trapped. It felt really liberating. Hi, friends. Today we're going to talk about drugs and psychedelics, the ones that actually create risk of harm, and also psychedelics that create some potential benefits. I personally did ketamine. I'm going to walk you through the data of what we saw in my brain and also talk you through the Don't Die kit. Everybody should have to make sure that people are safe for unexpected circumstances. We should do the podcast on mdma.

I'd be happy to do a whole podcast on mdma.

We should do sauna in the sauna.

I think all of our podcasts should be done while we're participating in whatever we're talking about.

That's a requirement.

Except for the last one.

This is analingus. This is AKA known as rimming, where someone uses their mouth, their tongue, their lips to stimulate someone else's anus for actual pleasure.

Yeah, analingus is going to be a hard one. Okay, who's up next? That's a pretty uncomfortable question, though. I mean, would you dare ask your friends, have you participated in Annalingus? Is that a topic that you dare broach?

Oh, for sure.

You would?

Yeah, without a doubt. I'd bring it up.

Yeah. And you would just basically flat out say, hey, like, what's your experience? Do you. How would you pose the question.

Just, you know, a flat out. Do you enjoy rimming?

So the assumption is they rim and the question is, do they enjoy it or not?

Yep. I mean, I feel like that's like a nice way to start the conversation.

And then the person has a way out if they can say, actually, I don't rim, because I listened to a podcast recently right by the Don't Diagnose.

Decided it was too, too high risk.

I didn't have a protocol in place, and therefore I thought I might want to get prepared before I engage in this activity. Mike, would you ask your friends if they engage in ribbing?

I don't think I would. I don't have the urge to know. I'm not sure I want to know. I mean, if you do know something like that, then do you. Do you avoid sharing like a cocktail or do you worry about, like eating after them? I don't know.

Do you share drinks with people, Mike?

Not usually, no. I prefer not to get infectious diseases.

Yeah. I feel like this could also be part. We should have talked about that on the Annalingus episode.

Yeah, I used to be much more casual about that. I would taste someone's drink if they offered it up. But now I don't share drinks, glasses, straws with anybody.

That was a fun segue.

We can take the different categories we talk about and we can rate each one according to what we find socially permissible. Permissible. I mean, Kate, you. You can bring up. Remain. Mike can't. I would feel the same as Mike. I would find it to be a pretty hard entry point to bring that topic up. 1. On what we're talking about today with drugs, I would say it's. It's probably more acceptable to inquire if somebody has used a given drug. You know, it's. It's okay to share your personal experience. Like, hey, I, you know, I smoked weed and I had this experience, or I did MDMA or I did psilocybin, or account someone else's experience. But it seems like it's a very socially friendly topic to discuss. If you get into things like coke and heroin, then it's less. I mean, I guess I'm trying to think through my experiences. Actually. People are pretty liberal in sharing their drug experiences across the board. Even in the past couple years, I think it's become much more liberal. What's your experience? Do people talk about this freely?

Well, what do you guys experience with your parents generation, for example? Is it like, would you dare discuss your drug use with your parents?

I think it depends on the drug. In my mind, psychedelics are way more accepted right now and kind of hot and almost like cool to talk about, maybe more so with the younger generation. But then sort of like Brian mentioned, like, I think people are a little less willing to talk about like coke, meth, heroin, things like that. But psychedelics seem like a, like a casual conversation that could just come up at a Party with somebody that you don't really know at this point.

Yeah, almost like you introduce the topic and it forms a, a friendship bridge that hey, we're part of the same tribe, we've had a similar experience, we can speak a similar language and, and share and then if you haven't it. Yeah. Is maybe a question of why. But I would say that yet in the past few years and probably because of the, the efforts that have been underway in getting the, the various like psilocybin and MDMA assessed for their site for their therapeutic properties in depression, ptsd. So the normalization and the, the clinical blessing going through the FDA path, even though they've had a difficult time doing that, that it's, it's conferred a bit more credibility and, and status. I mean I remember Kate and I went to health gathering in Texas and there was a, a gentleman there who was a. Like a world renowned chemist or something like that. But you know, he was in the scientific field and he recounted this story about his use of. Kate, what drug was it psilocybin that he used? Do you remember?

I want to say yes, either that or lsd.

But he. His on stage with, with a big crowd. He. Through the course of about 10 minutes he told a story of how he used this drug and how it had a meaningful impact on the ideas of his work projects and how it was a mind expanding experience, it was productive to the goals he had in life. And then his trepidation of sharing this experience with his fellow scientific colleagues and that he was so apprehensive to confess and share that he had done this because he was worried about the reprisal that they would ostracize him from the tribe. And to his great relief, the primary person whom he cared about for respect came back and was almost indifferent and almost congratulatory about his experience. And he felt this gigantic wave of relief. But I think what he was trying to share with the group is it's safe, it's okay even in social circles that have severe social penalties for violation of social norms. But I was pretty struck by that because in the conversations I have, there's not much inhibition at all in sharing your use of various psychedelics. So I guess still in some circles there can be a lot of negative repercussions that come from sharing. For example, even with parents, for example Kate, that it may not be a generational cross that people dare to do.

Yeah, I wonder if it's just the. Your circles are a bit more progressive when it comes to these things. Too, like, you know, startup sort of CEO. I feel like that's the tech. You know, that area seems way more open to this than like the more standard professionals. I don't hear a lot of lawyers like sitting around the, the fire talking about their psychedelic use, you know what I mean? Even physicians, for that matter.

Although, a side note, I was talking to my lawyer yesterday and I asked him a question.

Are you going to out your lawyer?

Where is this going? And in the pause as he was thinking about answering me, he. He went. He. He made the following sound like, like, like ChatGPT. And I thought, does he realize that he's. He's mimicking chat GPT's behavior like now? Maybe? Because I've known this guy for a long time and he has never made that noise. So. So just a sidebar of how we are becoming chatgpt. We posted that on Social. That's a tangent, but kind of, you know, we become that which we consume and we consume so much GPT. So today let's talk about that which we consume in psychedelics. A lot of people have asked the question, they are familiar with psychedelics as a vector for recreation and enjoyment and exploration and novelty. And also there's a question of are these psychedelics potential, I guess let's say drugs as a category, which includes psychedelics, are they potentially useful for longevity and health? We're going to analyze all the big ones and discuss their various properties of what they can potentially offer for improved health and also the potential downsides. Mike and Kate, before we did the research for this episode, were either of you aware of the range of possibilities with these various psychedelics?

What do you mean by range of possibilities?

Like the therapeutic interventions, therapeutic health, longevity, anything they would do in the body, potentially?

Yeah, I was pretty, pretty aware of it. Um, this has been an area, just a topic of interest for me for a long time. Um, so I also was like PI on one of the studies that we're talking about with longevity. So, yeah, super, super aware of the potential benefit, especially around like the mental health aspect of these, of these medications. So, yeah, I'm super excited to talk about this. I think this is gonna be a cool, cool topic that has been talked about a lot in, in the media. But the angle we're taking on it with the longevity I think is super cool.

I feel like my experience with drugs as, like they're kind of lumped into this party drug phenomenon and the downsides of some of these drugs that are quite severe, like literally cutting off just some of your Lifespan is somehow blurred with the more therapeutic side of some of these drugs that can help with mental health issues and a whole variety of things. So I find it interesting. I definitely, my experience is like, drugs are just lumped into this category and either you're okay with it or you're not. But we don't get into the specifics. So I'm really excited to dig into that today.

And this of course came up because somebody was trolling me on X and they used a picture of Hunter Biden and they said Hunter Biden at the age of 55, on a steady diet of ketamine and blow, looks better than Brian Johnson at 47 after micro calibrating the air in his sleeping room when he logs his boners. To which I responded, starting ketamine and blow today. And so that's what we're going to investigate is what properties of health and longevity do these various psychedelics have? And then conversely, we will look, talk about drugs such as cocaine, heroin and others and the potential risks that they face.

Can we take a minute and, and appreciate the quality of that trolling? I mean, it's upper level trolling, right?

This is always yes and never never no. But just, you know, when, when somebody pokes fun of you, the best move is always tsn. Play along, be the butt of the joke, you know, have a good laugh at yourself and you know, maybe, maybe it will lead you to good outcomes. Maybe. We're going to find that ketamine and blow are, are part of our blueprint protocol. So we'll see. Let's get into the science. Is it a good idea to start a protocol of doing lines? What health effects does can cocaine have on somebody?

Yeah, cocaine's pretty clear. Cocaine falls squarely in that category of can certainly and will kill you if you use it on a regular basis. So the studies on heavy cocaine use have shown a risk of death increase by about four to eight times higher than people who don't use cocaine, which is about a 20 to 40% reduction in life expectancy. So we're talking really big stuff. Um, there's been multiple studies looking at the effects of cocaine. So it's increasing your blood pressure. It's also an independent risk factor for cardiovascular disease. So you actually produce more plaque in your arteries just by using cocaine by itself. So using cocaine once a day equivalent to about 10.8 years of life lost on average. Uh, so I think like cooking is clear, it's bad news and there's, there's no longevity benefit.

That's Wild. That's such a significant amount of life lost.

I mean, that's actually very close to being on par with chronic smoking.

Absolutely. Maybe even a bit worse. I mean, some of those, you know, the four to eight times higher increase, I mean, those are heavy users, so maybe like heavy smoking users are more consistent as well, but slightly higher than smoking, I think.

Do we know what is it about cocaine that creates such high hazards?

So it's. I mean, it is very activating. Right. So it is a stimulant. And stimulants in general are. Are bad when it comes to cardiovascular health. I mean, you know, we see the same thing with methamphetamine. Really. Any stimulant is activating your cardiovascular system, increasing your blood pressure, increasing your sympathetic tone. All of those things over regular use and regular time is causing pretty significant challenges to your homeostasis of your body and is going to lead to high blood pressure, cardiovascular disease, stroke, dementia, all the bad stuff.

Would those same principles apply to things like Modafinil as well? I mean, they, of course are less intense than cocaine, but maybe fundamentally the same.

Fundamentally different mechanism of action is different. We actually don't really understand how, how Modafinil works in terms of keeping you awake. Um, it is a. It's not a stimulant in, in the classical sense. So it's not activating those particular receptors in your brain and throughout your body that a traditional stimulant is. It's working on different neurochemical pathways in the brain that are just keeping you awake, basically.

Okay, so probably not going to include BLO in the protocol. It sounds like. Is there any benefit to cocaine that we're aware of besides potential in the moment? Jo Joy, stop.

A nosebleed. It's great. It's like one of the best drugs you can use to stop it. And I mean, seriously. So, like, in the emergency, we would sometimes, in people who had really bad nosebleeds, actually like, shoot some cocaine. Very small amounts compared to what people.

Wow.

Like, for fun.

So you kept cocaine in the hospital?

Yeah, we had cocaine in the, in the drug cabinet. It was locked away and it was very hard to get to. And you needed like four people had to like, push a red button to get it out.

But yeah, but guaranteed crazy guarantee doctors are stealing that and doing that?

I don't think so. It's actually really hard to steal. The processing are pretty good in most. In most hospitals about getting those controlled substances. You have to have like multiple people take it out for you and Then you have to, like, have somebody watch you use it and then watch you, like, throw away the extra. So it's pretty. Pretty well regimented.

So, Mike, do we need to keep some cocaine here at the blueprint clinic just in case?

I don't think so. We probably need some psilocybin, just in case, But I think cocaine, we probably want to leave that one out.

And, Mike, is it a powdered form? At the hospital, it comes in a.

Powdered form, and then you reconstitute it in. In a liquid, basically.

Yeah.

To shoot into somebody's nose.

Oh, okay. As a spray.

Wow.

Okay. Fascinating. Who would have known?

I still don't bleed like, the.

You're not doing it. You're not, like, making a line for the patient.

Right. All right. And also like that, if it's a nosebleed that's really severe, it's like there's going to be other things that get in the way. It's very interesting.

That's a TV show that waiting to be happened. You're like, the doctor's punching the patient in the face. It's like behind the curtain, it's like, this patient needs some coke. Nurse, grab that. And then there's no way there's cocaine being held in the hospital. And people are not working in tandem to abuse it. They. I don't believe it.

I believe it. I believe it. What else have you got in the hospital, Mike, in our list of.

So, yeah, there's. This is definitely a tangent, but. So working in the va, we used to actually prescribe beer for some patients. Yes. So, like, alcoholic patients going through alcohol withdrawal who were there for, like, surgery or something like that. Like, one of the best ways to prevent withdrawal is for them actually to drink. And you don't want them to withdrawal if they're just going to go home and continue drinking. So you don't force people through withdrawal in those situations. Usually give them some sort of medication to help prevent withdrawal. Because withdrawal can kill you. Right. Alcohol withdrawal can kill you. So we would literally. So also in the Pyxis, which is the name of that device that holds all the drugs, there's also a can of beer. So, like, describe cocaine. A can of beer. Yeah. There's all kinds of stuff in there.

Wow. And there's. There's no drug to act like alcohol without being alcohol.

There are. And realistically, you can combat the withdrawal symptoms, but for whatever reason, the actual act of drinking, it's better for some people. So there were cases where some people who were sort of resistant to the regular medications we would use for withdrawal. You would just prescribe them a beer and they would have a beer in addition to those drugs that you're also giving them.

On the topic of emergency drug situations, fentanyl is in a lot about drugs on the market, especially here in the US and in cocaine specifically. So if you are going to do cocaine, Mike, what is the protocol for it?

Yeah, so fentanyl is like a whole nother thing. First off, like, I'm not sure I can give anybody a protocol for doing cocaine. I think, I think our protocol for doing cocaine should be you should not do cocaine. But like, realistically, people are going to do things that we tell them not to do. They already do that. So not just cocaine, but really any street drug, you need to understand the risk with fentanyl. And the reality is that in 2023, the DEA released this study where they looked at all fake prescription pills that were taken off the street and something like 70% of them had high doses of fentanyl in them. And this is true across just about any street drug. Not even classically, you hear about this with heroin being cut with fentanyl, but it's actually happening with MDMA pills, it's happening with fake opioid pill, that's happening with cocaine. All kinds of stuff where we're seeing fentanyl. And the problem with fentanyl is per gram, it is extreme. It is, it is like a hundred times stronger than a standard other drug. So a very, very small amount of it, amount of it in your pill is enough to kill you. And what we're seeing is about a hundred percent increase in fentanyl related deaths year over year, the past few years. And this is because more and more drugs are being cut with fentanyl. So the reality is if you're going to use street drugs, cocaine, mdma, anything you don't buy from a pharmacy, you should really have on hand naloxone. And you can buy this online. Like you can go online for like 15 bucks, buy two doses of like nasal naloxone spray. And that should be on hand for you, for your friends. Like in my opinion, pretty much everyone should have it, you know, in their car, on their keychain, whatever, in case somebody goes down and they're unresponsive. Because the first thing you should do is give them that shot, or it's a nasal spray. Give them that nasal spray and you could very well save their life.

Wow.

And it's also important to recognize that like it's, you should also, beyond just having that rescue drug available, you can also purchase fentanyl test strips, where you take a little, little tiny piece of the pill or the drug or whatever you've purchased and like, put it in a solution and the solution changes color if there's fentanyl in it. And if there is fentanyl in it, you should not take it, because there can be so much fentanyl in one single pill that even the rescue spray won't save your life. If there's enough of it, you can have an opioid overdose without any rescue possible.

And you can just get those test strips on Amazon. They're available easy.

Yeah.

Is that the same that spray that you mentioned? Is that the same strength and type of drug that someone would get if they went to the ER and they were suspected of having?

Exactly the same, yeah. There's been a big push to have it more available in the community because obviously most people can't get to the ER by the time that it's too late. So I saw this a ton in emergency medicine. Way too familiar with, with fentanyl overdose. And this is, I think, an underappreciated problem in our society today and something that we should be be very clear about and talking about this particular topic today, I think. But with the exception of cocaine, we're going to end with a very positive note for a lot of these drugs. And I think it's also important to recognize that, like, this is uncontrolled, so people should have a protocol for how to prevent potential harm with taking any of these drugs. And part of that protocol includes naloxone.

Mike, would it be a good idea for. If you. If you or your friends use drugs on some kind of basis, for you and your friends to have this on hand in case you run into a problem? Would that be a good practice for people?

Yeah. I've purchased these, which I keep at my home and in my car, like, just in case I come across somebody who needs it. And I haven't decided exactly when the time is, but I will be getting a keychain for my daughter that has one of these nasal sprays in it.

That's amazing.

And my son. Yeah, I mean, like, I think this is something everyone should be acquainted with. We should not have any hesitation talking about this. Like, the reality is people use drugs. The reality is there's fentanyl in everything, and we should be willing to carry these things around to save people's lives.

I just look this up. I don't fact check me on this, but I'm seeing a stat here. Fentanyl poisoning is the leading cause of death for people aged 18 to 45 in the U.S. true. Wait, like, we're talking about longevity. And the cohort of people that aren't susceptible to, like, aging diseases that accumulate across time are dying from this drug.

This is the most important part of this conversation today. 100%.

Wow. That's insane.

Okay, so two things. Get the fentanyl test strips and the Narcan nasal spray.

Narcan. Is that the same as naloxone? Naloxone. Okay, fascinating. And, Mike, is there any scenario where if you're not sure if someone's having a fentanyl overdose, do you give them the drug? Like, is there any downside to having.

This drug you give it? Worst case scenario, they're somebody who is habituated to opiates because of chronic pain, and they take up opiates on a regular basis. But if they're unresponsive, they. That means they've taken too many opiates. So worst case scenario is they wake up in pain. That's literally the worst case scenario. And if it all.

It.

It only acts on opioid receptors, so you're not going to cause anything else. Like, without a doubt, somebody's unresponsive. Like, while you're checking your pulse. Their pulse, you should be shooting this up their nose.

Okay, so unresponsive. They've got a pulse. I mean, obviously, call an ambulance.

A hundred percent. Yeah, yeah, yeah. All the. All the basic stuff. This isn't it. This is a intervention that could potentially save their life. While you're doing all the. Call 911, check for pulse, do CPR, all of those things.

If I was to take Narcan right now, would it have any effect on me?

If I'm not, you know, you wouldn't notice a thing.

Wow. So really low, low risk drug. Well, that was a really important detour. I'm glad we covered that because that's. I'm absolutely inspired now. I will get a keychain version, so. Thanks, Mike. Okay, so below is a little high risk in that it reduces lifespan and also might be cut with fentanyl on the market right now. What about ketamine? Is this something that would be good for longevity?

Yeah. So ketamine's interesting. Ketamine is a drug I'm extremely familiar with. We use it a lot in medicine as basically an anesthetic. So we are knocking people out with ketamine to do procedures, sometimes for surgery. And it is a very safe drug when used appropriately, has a very low risk of severe side effects. And the interesting thing is it's gotten a lot of attention recently. I'm sure you've noticed there's all these ketamine clinics popping up. There's some studies that have come out that it can be very beneficial for PTSD and for depression and for anxiety. And now people are starting to use it for chronic pain. So lots of interesting stuff. We can go through that if you're, if you're interested. But there's been also a study on ketamine specifically for longevity, which is actually a study I was involved in, in performing. But we had 20 patients with depression who got six ketamine infusions. So they went to an IV ketamine clinic, got six infusions and they, they did it for treatment of their depression or ptsd. And we saw of course that they had significant reduction in their depression symptoms, which is consistent across lots of studies. That's Nothing new about 50% reduction in self reported surveys. But what was really cool is we did epigenetic tests before and after their six ketamine infusions and we saw consistently a reduction in their epigenetic or biological age over those six infusions. So pheno age decreased by 2 years, grim age by 1.1 years, omic age by 1 year, their brain age by 1.5 years. Lower inflammation down by 2, metabolic down by 3. So across the board we were seeing people actually appearing to be like not just mentally healthier, but also physically healthier in a reduction in their biological age, which was I think super interesting. And it does sort of mechanistically, doesn't necessarily make a lot of sense unless you believe that there is this like, sort of like, you know, body brain connection. Right? You improve the brain, the body follows along.

Interesting.

You improve the body, the brain follows along with it, which I, I tend to believe in. But there's not, there's not clear mechanistic examples yet.

Mike, we were talking yesterday about this preprint that some people on social media were saying that ozempic lowered biological age. And that wasn't what the paper said. The paper was showing something else in this case. Do you think that it's the ketamine that is the contributor to the reduced biological age or do you think it's the improvement of the condition, the depression that is then having that effect, or do you think it's a combination?

My guess it is that it's the change in the depression. So the the all of these people had significant reductions in, in their, their, their self reported depression and PTSD symptoms. And my guess is that they are making, I mean you think about like what happens if you go from being severely depressed, ptsd, what sort of life choices do you make as compared to if you improve all of those symptoms, you likely track with better life choices based on all of those best based on that improvement that you've had mentally. So my guess is this is all secondary. I, I mean there's no way to know whether this is truly causal or not. I mean there's 20 patients and it, you know, it wasn't like completely controlled. So it's hard to know if there's causality here directly from the ketamine or if this is a secondary effect of improving the mental health of the, of the participants, which is my guess.

It's fascinating that ketamine has such an impact on the brain because Brian, we, we literally studied this at Colonel you, kernel is a device that measures your brain activity and then you did ketamine, you measured before, during and after. So what happened when you did ketamine?

This was so cool with, with Colonel we were trying to enable what happens when. And you know, our, our entire life is built around these basic hypothesis, these basic experiments like what happens when you sleep well, how do you feel and how do you function, what happens when you don't sleep well, what happens when you eat this kind of food, what happens when you study or in this case we were asking the question what happens to the brain when you take ketamine? And because measuring the brain is so hard to do, it's expensive and hard, there was very limited data on getting real time information on the brain. So we did an experiment where I wore kernel flow for several days before I did ketamine and then I wore it during ketamine and I wore it for days afterwards. So it was the first in world demonstration of capturing changes to brain activity. Now kernel is a, it uses a technology called time domain functional near infrared spectroscopy. It's basically like a, a pulse oximeter that you put on your finger for the brain. So it uses light that's safe and then it maps your brain activity. So the first image of what happens to my brain before ketamine and after Ketamine. So you see that before ketamine, on days one through five, my patterns are very stable. They're the same day in and day out. And then I do ketamine and my brain patterns scramble. So on day two, three, four, they're substantially different. And then towards the end of four and into five, my brain patterns start to normalize again. So this is what people refer to as the therapeutic window, where you do a session of ketamine or some of those psychedelic and it opens the mind up to new ideas. And so the way to think about this is that your brain has nodes of networks of communication. And so think of it like planet Earth with airports and planes are flying from node to node, you know, New York to Tokyo. And some nodes have more traffic patterns than other nodes. And when you do ketamine, it's like you just pick up all the airports in the world and you scramble them. The existing nodes and networks change about, but that only happens for a few days. And then, you know, by day four or five, they go back to where they were. And so that's why there's wisdom in trying to adapt to new patterns of thought and behavior in this therapeutic window. And I guess I did this actually unknowingly in the office, I think. Kate, you were with me when this happened.

Yeah, I'm laughing because you did this unknowingly.

Rewind that one for me. I'm just walking down the moon.

No, he's going to finish that sentence. But I remember, I'm laughing so much because I remember like coming to pick you up, Brian. And it's just like, it's funny, these experiences. And you were so different. Those, like next couple days you were just like. Yeah. A different human to interact with.

Yeah. We were at the office. I went back to the office the next day and we were walking to another room for a different meeting. And there was a big wall in between, like probably like a five foot wall, like a pretty sizable wall. And instead of walking around the office to get around it, I thought, why don't I just jump over the wall? That makes much more sense. And so I just jumped over the wall and I didn't think about it. And my coworkers were like, brian, what are you doing? That is really odd. And I thought, oh, you're right. I guess that might be a little odd. Yeah, my behavior was definitely changed and I was open to different ideas and I wasn't as trapped. It felt really liberating. And then also we'll throw up on the screen here. The. The effects of my. So my brain activity for the first 5 to 15 minutes post injection and then the effects of 15 to 25 minutes after injection and you see how dramatically my brain activity changes. So this was amazing to see. We spent heart and soul and years building this brain interface. It's like a wearable high fidelity brain interface that does not exist in the world. And it allowed us to do this amazing experiment to show that we can capture the effects of ketamine and any other psychedelic on the brain in real time. And it meaningfully changes how your brain processes information in that moment and also for days afterwards. And the final graph we'll put up there is how ketamine affects the brain over time. And so you just see a graph where it's very steady leading up until the dose and then you see these huge oscillations and then it kind of dips down and then steadies back out. So cool to see the pattern. So this is just like we measure everything else at blueprint, whether it be blood glucose or cholesterol or anything else. Now we have kernel to, to measure this high fidelity brain activity. So that was cool to see what otherwise people just talk about it in a subjective way. They take questionnaires and say I feel this way or the subjective reporting is really unreliable and not all that interesting.

I like the way you describe it too with the airports and the nodes because to me that explains well why these medicines, why these drugs can be so powerful with depression, ptsd. Like let's take for example like a trauma scenario, right? So you've got like a flight from San Francisco to New York. That's your, that's your trauma connection in your brain, right? And if you're so used to taking that, that one flight, it's hard for you to imagine going from San Francisco to Seattle to New York, right? But maybe that San Francisco to Seattle, New York is the non trauma pathway, right? So it, it's like taking this medicine opens up all these additional nodes so that you can create new pathways and byp these ruts that the brain gets in when it comes to mental health. So it's just really interesting to think about it from that way and see the actual images showing these new connections being created and explaining this opportunity, this window of opening. I saw an interesting study recently on different psychedelics and they were looking at the duration of the psychedelic and they correlated that with the therapeutic window duration after taking the psychedelic. Ketamine was like a few days as, as you saw with, with, with colonel but like some of the longer acting ones like Iboga, which lasts for like upwards of 72 hours was like months, like your therapeutic window is open for months. MDMA was I think like around a week. LSD slightly longer because it's a 12 hour duration. But it was really interesting. Like the duration of the psychedelic was associated with the duration, duration of the opening window afterwards.

Wow, that's really interesting. So can you actually explain therapy, Therapy window, Is that when you want to intervene to kind of try to like. Yeah, what, what is that?

The way I think about it is it is the window of opportunity to continue focusing, right? So people talk a lot about. There's this discussion around this concept of integration after a psychedelic experience. So you have a psychedelic experience, lots of crazy stuff happens. You know, maybe you, you know, like relive an old life or you meet these architect ar. Architectural like, you know, creatures or whatever happens. Like some, some stuff happens after that time frame. You can continue to do, quote, unquote, work on whatever you're trying to manage in your life and you are more likely to be successful during that time frame. So, like, if you're going to do psychedelic assisted therapy, for example, you want to focus a lot of that therapy during that therapeutic window after the psychedelic experience, because at some point your brain kind of goes back to. I wouldn't say it's old ways, but it's. But it kind of like hardens. Imagine like wet cement, right? Like right after the psychedelic experience, you've kind of got wet cement. You can mold things how you want it, but after a certain number of days, depending on what you've taken, it starts to harden and form and it's going to be harder to create those new connections. So your plasticity of your neurons goes down and you've got less ability to mold things the way that you want them. That's kind of how I think about it.

Mike, in our research preparing, we identified a way to a paper of how to prolong ketamine's therapeutic window. Do you want to go through that detail of how people take this opportunity and try to extend it?

In the study that you guys were talking about, the researchers found that basically you can boost a specific signaling pathway in the brain, something called the ERK pathway, which can sustain the therapeutic window of ketamine so that it's much longer. And what they did is basically they took mice and they combined ketamine with this drug called BCI, which inhibits DUSP, DUSP6 or something like that, which elevates ERK activity and helps reinforce those neural connections in the hippocampus, which is where the brain remembers everything. That's like the memory center of our brain. And what happened was when they did that, they found stronger connections between the neurons and more antidepressant like behaviors which lasted eight weeks as opposed to what we typically consider the duration for ketamine, which is like, you know, around a week or maybe a little bit less. So really interesting that you can sort of combine medications to prolong that effect. And that's something that I'm not aware of being done clinically right now, but it's something that I think we could look at in the future, especially if we start to see psychedelics come more into, into clinical acceptance as tools, which they should, based on the research we're seeing.

I'm just like imagining you're creating your longevity protocol right now.

We should do a few experiments. I mean now that we can measure the brain with kernel, we should do a ketamine experiment with this enhanced effect of increasing the ERK pathway. So we should basically do ketamine with bci, try to extend the therapeutic window and Yep, I wonder what else we could pair with this. Like if, if the therapeutic window is open and it's creating space for new things, I wonder what we could try to do in that window which would be measurable.

Interesting.

Can we, can we measure the effect of my plasticity?

We could try to teach you something new so we could potentially have you learn a new language. We could have you learn a new instrument so we could. I'm not sure how we control for it, but like one thing that plasticity has been shown, like opening these plasticity windows has been shown to be beneficial not just for mental health benefit, like you know, retraining, trauma pathways, but also just for like learning in general. So we could do different types of learning or learning tests. Memory, memory and cognitive, cognitive testing and see how you perform during this window as opposed to when the window's closed or prior to opening the window.

Yeah, I like that a lot. And so we can do academy here in the States. We could. The ibogaine. We would probably need to travel to.

South America or Mexico. Yeah, there's. There is not too far from you. There's a pretty popular clinic in Tijuana that's done some amazing work in war vets. They've shown. So ibogaine is interesting, like personally a little scary because it lasts like 72 hours. But the studies out of Stanford for PTSD and brain injury, post traumatic stress and post concussive syndrome or post brain trauma in vets have been really impressive. So upwards of like 85 to 90% remission of complex PTSD. So like just to put that, like that Sounds cool. Yeah, 90% remission. But like just to put that into context. The remission rate from like, SSRIs plus therapy for PTSD, not even in complex PTSD is like 30%. So the best medicine has to offer right now is like 30% remission. We're talking about a drug with a single intervention, 90% remission. That's 3x the outcome, which is pretty crazy. I mean, like, you don't, you don't hear about this stuff in pharmaceutical, in the pharmaceutical industry. This is crazy.

What else could we measure? So if we did neuro effects with Kernel, would we look at. I mean, we'd have all the wearable data. Would we look at mitochondrial function, methylation changes? Like, what else would we look at for a comprehensive panel of what, what effects? What are the things happening in the body when you do something like hippogain?

This also gets to your brain. Body connection. Mike?

Yeah, this is tough. I mean, like, we're talking about things that. The predominant pathways that are interesting and beneficial are happening in the brain. Brain is inherently hard to measure. Right? Which is why Kernel is so interesting. But it's challenging to measure these, these pathways. So, like, you look at these studies on psychedelics, they're predominantly like FMRI or, you know, either they're either like, let's give them a survey and ask them questions about how they feel, or they're like super expensive, complicated FMRI studies where they're looking at, like, glucose uptake in certain brain regions because the brain is inherently hard to measure. So we're kind of stuck with, like, we're either like, surveying your subjective experience or we're actually, like, visually looking at the brain. Beyond that, there's not a lot of, like, biochemical changes that are gonna be easy to measure. It'd be interesting to look at, like, S and B. Right? That would be. That would be super interesting, like, looking and seeing. Is there a change in, like, inflammation? Because there might be a temporary, like, increase in brain inflammation after. After psychedelics. I'm not sure, to be honest. Like, this stuff isn't well studied. So there's a wealth of opportunity here. Like, we could start with your. The basic panel that we do for you with, you know, all of our inflammatory markers and looking at all of our meth inflation markers and all those things and see if we see any changes. But my guess is the majority is going to be hidden inside the brain and it's going to be a, like, neurochemical pathways rather than things that we see systemically.

Kate, what do you think? Should we, should we plan this out?

I think this is a cool idea. I think it'd be really cool to do this in a therapeutic setting and systematically, like, do an experiment. Let's go to Mexico.

Exactly. I'm just thinking through all of the conversations I have with my friends on various things and realizing how difficult it is to really get your head around health. I mean, we live this every day, all day on all these topics, but it's pretty hard to make sense of all this and specifically to get robust measurement around a given phenomena, like what happens when. And I think most people give psychedelics the benefit of the doubt because they, they kind of have a halo effect where they're viewed as protagonists in society, whereas cocaine and heroin are more viewed as antagonists. But even with the protagonist halo, a lot of people don't understand the, the nuanced effects of them. So I think this would be really helpful to, I mean, for example, even talking about that therapeutic window that if you do do it, you have that opportunity to change yourself. And so something more specific in terms of what can you do in that window of time to make changes that you've wanted to be. Wanted to make, but just haven't for a variety of reasons. And if we could add additional data on what else is happening inside the body, it might help people build out more robust models of why they're doing this. And that more robust comprehension, I think, would just help them be in a better state of mind that preparing themselves to go into it with a different intent.

You can imagine how an experience like this could allow someone to create the behavior change necessary for longevity. Right? Like, oh, interesting. In so many ways. This is kind of like the potential for like a key to behavior change. Right. I mean, ultimately that's what a lot of people's goals are. I mean, so obviously some people are coming forward for depression, for ptsd, for, you know, like these, these true, like diseases that, that they need help with. But like other. There are people who are using psychedelics for just personal growth. And in a lot of ways, I think what those people are looking for is the, I want to say motivation, the, the energy to overcome the inertia of personal change. And that therapeutic window can be the opening and that that initial energy needed to propel people forward.

Mike, I have this idea in my mind that ketamine is addictive and that it also has potential bladder related issues. Are those things accurate or is that hyped up by pop culture?

A little bit hyped up, but it's true. I mean, ketamine does have some very minimal but some addictive potential ketamine is. So just like to take a step back, ketamine is very different than the classical psychedelics. So it's working on the nm, NMDA receptor as opposed to the serotonin receptor. So all your classical psychedelics work on the serotonin 2a receptor and that includes DMT, LSD, psilocybin, even MDMA works a little bit on that receptor, although it also hits dopamine. But all of the like 5 Meo, DMT, all the classical psychedelics are working on that serotonin receptor whereas ketamine is working on nmda. So ketamine can be addictive, it's minimally addictive. It's more like psychologically addictive than it is truly physically addictive. Right. I mean it's, I, I don't really like making those differences cuz addiction's addiction, um, but it is, it does have more abuse potential as opposed to the classical psychedelics where like you, if you keep hitting that serotonin receptor it just stops working. Like not forever but like if you did psilocybin and then two days later did psilocybin again, the second experience would be extremely minimal because all those receptors are kind of, they're like, I've seen this, I'm not doing that again. Whereas like ketamine you could do it like hour after hour and pretty much get the same response over time. So it's a little bit more addictive. There have been reports of, with extremely regular use, these interstitial cystitis bladder type issues have been reported for sure. But and when it comes to a therapeutic drug for the indications we're talking about, extremely safe, extremely safe at that level of use.

One last question on this. Well, firstly to clear the air for ketamine because I feel like a lot of people think of it only as a party drug or only as a horse tranquilizer. Whereas like you said Mike, it was like in the 1960s that we first started using it in the medical setting for anesthesia specifically like for folks that can't take typical anesthetics. Right. Is that right?

Yes, I mean like, but now to the point where it's used like preferentially because it's so safe as opposed to a lot of anesthetics. So if you go to have surgery you're probably not going to get ketamine but if you go have a short procedure in the emergency department or in a pediatric unit somewhere like that, it is often the anesthetic of choice. So yeah, I've given it 10,000 times in a hospital setting.

So from my colloquial understanding of ketamine, you know, you can. So it sounds like you can be completely knocked out, is that right? And then you can be in a K hole where you're physically paralyzed and then you can have a more lighter experience. Is there a better therapeutic place to be or do they all have benefits?

So ketamine, you can go as low as, you know, like a just barely, barely feel it, what we call a psycholytic dose, where basically you just barely feel a little bit more open. This is often used for, like psychedelic assisted therapy, where you take a little bit of ketamine and then you have a conversation with a therapist. Right? You can go all the way from there to like getting dropped into the quote unquote K hole at an IV infusion clinic where you basically get knocked out and hardly remember anything or have this like, out of body experience experience. And you see about a lot of geometric shapes and like come out of it feeling like, you know, you, like, met God or like watched yourself from outside of the room or something like that. So there's a wide range of experiences that you can feel. If you get it as an anesthetic in a hospital setting, you're likely going to get put in the quote, quote, unquote K hole where you just get knocked out and you're completely out of it and chances are they're going to give you something in addition to it. So it's not like a real out of body experience. You, you just feel kind of knocked out and you wake up, right, wake up later. Um, but yeah, it can go all the way to like, you don't remember anything if you take really high doses of it.

We had quite a few other psychedelics on today's agenda to talk about. I think we're going to wrap this episode now. The summary is cocaine is not a longevity therapy. It is going to dramatically shorten your life. Two is it's a good idea to have a don't die test kit. So a don't die drug kit, which includes fentanyl test strips and the nasal spray, it's just good to have on hand. You do not want those kinds of mistakes. And with it being a leading cause of death, it really is not something you want to mess with. And then finally is ketamine is very promising, that we know from a lot of research and also my personal data that it is promising on the effects of ptsd, of depression, of opening therapeutic windows of change, and also that it has the ability for the therapy window to be extended with new research that was on animals, not on humans. So also, I think it's giving us an invitation that we probably want to design a protocol and test this out ourselves and to see if we can quantify the effects of ketamine and extend the window and see if we can measure plasticity through some kind of learned behavior. So that's interesting as a new thing which we stumbled upon. Oh, then also, also we, we, we discovered that Kate is very comfortable asking her friends if they rim. And Mike and I do not necessarily approach that conversation. So question for you is, do you feel comfortable asking your friends their level of enjoyment of rimming or is it still something that is not appropriate in your circles?

Let us know next week. I'll report back. Does my circle of friends.

Does your circle of friends appreciate that or not?

Yeah.

Yeah.

And, and your brazen assumption that they rim, that you didn't even acquire. Do you. It was, your question was, do you enjoy rimming? It was not like, do you rim? So the assumption is embedded in that.

Well, because I want to lean on the side of giving them grace to say yes. It's a taboo topic. So if they do, I want to create the space for safety.

I see it's much safer than. Yeah. To make the big jump and say I do rim and I do enjoy. So they have to make just a one baby step versus two.

Right. Exactly.

Kate, that is very. That was very courteous of you. And it's a very Kate move to always be thinking about the other person's emotional needs. How could I, how could I expect anything less?

We'll see. We'll see what they say.

Okay. Until next time, friends, be well. This is the Brian Johnson podcast. Special thanks to my co hosts, Kate Tolo and Dr. Mike Mallon. For more science breakdowns and protocols, subscribe to my YouTube channel, follow the podcast on your favorite platform or follow me on Instagram or X at Brian Johnson.