Cocaine, Fentanyl, and Ketamine: Bryan Johnson and Team Put Drugs to a Longevity Test
Bryan Johnson
In this episode of the Bryan Johnson Podcast, Bryan Johnson, Blueprint co-founder Kate Tolo, and Dr. Mike Mallin, Johnson's lead physician, ask whether recreational drugs and psychedelics have any place in a health and longevity protocol. The hosts treat drugs as distinct substances rather than one category. Cocaine, in their account, is plainly harmful. Fentanyl contamination is the most urgent safety issue in the conversation. Ketamine is the substance they find most promising, partly because Johnson took it while wearing a brain-imaging headset his company built. They planned to cover more psychedelics but ran out of time and ended after these three topics.
A Troll Becomes an Episode
Johnson says the episode began with a post on X. Someone shared a picture of Hunter Biden and wrote that Biden, at 55 and "on a steady diet of ketamine and blow," looked better than the 47-year-old Johnson despite all his measuring and optimizing. Johnson replied that he was "starting ketamine and blow today." The hosts decided to take the joke seriously and look at what each substance actually does to health and lifespan.
Johnson says his approach to being mocked is always "yes, and": play along, be the butt of the joke, and see where it leads. He joked that ketamine and cocaine might end up in the Blueprint protocol.
How Openly People Discuss Drug Use
Before the science, the hosts discussed how socially acceptable it is to talk about drugs. Johnson said it seems fine to mention personal experiences with cannabis, MDMA, or psilocybin, and that people he knows share freely across the board. He thinks talk about cocaine and heroin is less comfortable. Mallin agreed that psychedelics now seem "hot" and almost cool to discuss, something that could come up casually at a party with a stranger. Harder drugs such as cocaine, methamphetamine, and heroin, he said, are still mostly off limits.
Johnson suggested that bringing up psychedelics can work as a "friendship bridge," a sign that two people belong to the same tribe. He credits part of the shift to efforts to evaluate psilocybin and MDMA for depression and PTSD through the FDA. Even though those efforts have struggled, he believes the clinical path has given psychedelics more credibility and status.
Johnson then described a talk he and Tolo saw at a health gathering in Texas. A prominent scientist, whom Johnson described as a chemist or someone in a similar field, spent about ten minutes on stage describing his use of what Tolo thought was psilocybin or possibly LSD. He said it had expanded his thinking and helped his work. He had been afraid to tell his scientific colleagues because he expected to be ostracized. When he finally told the colleague whose respect mattered most to him, the reaction was indifferent, even congratulatory, and he felt enormous relief. Johnson took the scientist's message to be that it is safe to share even in circles with harsh penalties for breaking norms. Johnson was struck by this because, in his own conversations, people show little hesitation. Tolo suggested that Johnson's circles, startup and tech CEOs, are more open than professions like law or medicine, and that sharing drug use with parents may still be uncommon.
Cocaine: No Longevity Case
Mallin was direct about cocaine: it "can certainly and will kill you if you use it on a regular basis." He cited studies of heavy users showing a risk of death roughly four to eight times higher than in non-users, which he translated into a 20 to 40 percent reduction in life expectancy. He added that daily cocaine use corresponds to about 10.8 years of life lost on average. Johnson compared this to chronic smoking. Mallin agreed and said cocaine may be somewhat worse, while noting that the four-to-eight-times figures come from heavy users.
Mallin explained the harm through cocaine's action as a stimulant. He said stimulants in general, including methamphetamine, activate the cardiovascular system, raise blood pressure, and increase sympathetic tone. Over time this disrupts the body's homeostasis and leads to high blood pressure, cardiovascular disease, stroke, and dementia. He also said cocaine is an independent risk factor for cardiovascular disease, meaning it adds arterial plaque on its own.
Johnson asked whether the same concerns apply to modafinil. Mallin said its mechanism is different and not well understood. He said it is not a stimulant in the classical sense and does not act on the same receptors. It works on other neurochemical pathways that keep a person awake.
Cocaine and Beer in the Hospital
When Tolo asked whether cocaine has any benefit beyond momentary pleasure, Mallin said it is one of the best drugs for stopping a nosebleed. In the emergency department, he said, doctors would sometimes use very small amounts, far less than recreational doses, for severe nosebleeds. The drug comes as a powder that is reconstituted into a liquid and sprayed into the nose.
Johnson insisted hospital staff must be stealing it. Mallin disagreed. He said controlled-substance procedures in most hospitals are strict: several people have to be involved in retrieving the drug, someone watches it being used, and someone watches the leftover being discarded.
Mallin added a related story from his time working at the VA. Staff sometimes prescribed beer to alcohol-dependent patients admitted for other reasons, such as surgery. Alcohol withdrawal can be fatal, he explained, and there is little point in forcing someone through withdrawal if they will go home and keep drinking. Medications are usually used to prevent withdrawal, but some patients who did not respond well to them received a beer alongside those medications. The Pyxis, the hospital's drug-dispensing cabinet, held a can of beer next to the cocaine.
Fentanyl in the Street Drug Supply
Tolo raised fentanyl contamination, which Mallin treated as a separate and more serious issue. He said he could not give anyone a protocol for using cocaine, and that the real protocol is not to use it. He acknowledged that people will do things they are told not to do, so anyone using a street drug needs to understand the fentanyl risk.
He cited a 2023 DEA analysis of counterfeit prescription pills seized on the street, which he said found that something like 70 percent contained high doses of fentanyl. He said contamination is not limited to heroin but is appearing in MDMA pills, fake opioid pills, and cocaine. His concern is fentanyl's potency: he described it as roughly a hundred times stronger per gram than a standard comparable drug, so a tiny amount in a pill can kill. He also said fentanyl-related deaths have roughly doubled year over year in recent years as more drugs are cut with it.
Tolo looked up a statistic during the conversation and asked not to be held to it: fentanyl poisoning is the leading cause of death for Americans aged 18 to 45. Mallin said that was true. Johnson called it the most important part of the conversation, pointing out that it kills the age group not yet exposed to diseases of aging.
Naloxone and Test Strips: The "Don't Die Kit"
Mallin's practical advice was that anyone using a drug not bought from a pharmacy should have naloxone on hand. He said two doses of nasal naloxone spray can be bought online for about $15, and in his view nearly everyone should keep it in the car, on a keychain, or somewhere accessible. He said the nasal naloxone available to the public is the same drug an emergency room would use. There has been a push to make it available in the community because most people cannot get to an ER in time.
He also recommended fentanyl test strips, which Tolo noted are available on Amazon. A small piece of the drug is dissolved in a solution, and the solution changes color if fentanyl is present. If it does, Mallin said, the drug should not be taken, because a single pill can contain enough fentanyl that even a rescue spray cannot reverse the overdose.
Tolo asked whether naloxone should be given when it is unclear if someone is overdosing. Mallin said yes, without hesitation. In the worst case, the person is a chronic pain patient habituated to opioids, and since they are unresponsive, they have taken too much anyway. The downside is that they wake up in pain. Naloxone acts only on opioid receptors, he explained, and someone without opioids in their system would not notice anything if they took it. He said it should be given while checking the person's pulse, calling 911, and starting CPR, not as a replacement for those steps.
Mallin said he keeps naloxone at home and in his car in case he comes across someone who needs it. He plans to give his daughter and son keychain versions, though he has not decided when. He argued people should have no hesitation talking about this because people use drugs and fentanyl is showing up everywhere. Tolo said she would get a keychain version, and Johnson summarized it as a "Don't Die kit": fentanyl test strips plus Narcan nasal spray.
Ketamine as a Medical Drug
Mallin said he knows ketamine very well from clinical use. It is used as an anesthetic, often for short procedures in the emergency department and in pediatric settings, and he said he has administered it about 10,000 times. He described it as very safe when used appropriately, with a low risk of serious side effects. Tolo noted that it entered medical use in the 1960s. Mallin said it is now often the preferred anesthetic for certain procedures because of its safety, though a patient having major surgery probably would not receive it.
Mallin said ketamine has drawn new attention because of studies suggesting benefit for PTSD, depression, and anxiety, and because people are starting to use it for chronic pain. He mentioned the ketamine clinics that have appeared as a result.
A Small Study on Ketamine and Biological Age
Mallin then described a longevity study he helped conduct and served as principal investigator on. Twenty patients with depression or PTSD received six IV ketamine infusions at a clinic. Self-reported symptom surveys showed about a 50 percent reduction, which Mallin said is consistent with many other studies.
The new part was epigenetic testing before and after the six infusions. Mallin reported consistent reductions in estimated biological age: PhenoAge down by 2 years, GrimAge by 1.1 years, OMICmAge by one year, and brain age by 1.5 years. Inflammation and metabolic measures fell by two and three, respectively. He said participants appeared not just mentally but physically healthier.
He was cautious about the cause. He said the result does not make obvious mechanistic sense unless one accepts a strong brain-body connection, which he said he tends to believe in, but clear mechanisms have not been shown. Johnson brought up a recent preprint that social media users had misrepresented as showing Ozempic lowers biological age, and asked whether ketamine itself or the relief from depression was driving the change. Mallin said his guess is that it is secondary: people who move out of severe depression and PTSD probably make better life choices, and those choices show up in the markers. With 20 patients and no fully controlled design, he said, there is no way to know whether the effect is directly caused by ketamine.
Johnson's Ketamine Session on Kernel
Tolo turned to Johnson's own experiment. Johnson founded Kernel, which builds a wearable brain-measurement device, and he says measuring the brain is expensive and difficult, so real-time data has been scarce. He wore the Kernel Flow headset for several days before taking ketamine, during the session, and for days afterward. He calls this the first-in-world demonstration of capturing such changes in brain activity. He described the technology as time-domain functional near-infrared spectroscopy, which he compared to a finger pulse oximeter for the brain: it uses safe light to map brain activity.
According to Johnson, his brain patterns were very stable on days one through five before ketamine, looking nearly identical day to day. After the dose, the patterns "scramble," appearing substantially different on the following days and then beginning to normalize around days four and five. He also showed images of activity in the first 5 to 15 minutes after injection and 15 to 25 minutes after injection, which he said showed dramatic changes, and a timeline graph that is steady before the dose, oscillates heavily afterward, dips, and then levels off.
His analogy is a world map of airports. Brain networks are like airports with planes flying between them, such as New York to Tokyo, and some routes carry more traffic than others. Ketamine is like picking up all the airports and scrambling them. The existing networks shift, but only for a few days before returning to roughly where they were. Johnson says this is why people talk about a therapeutic window after ketamine and other psychedelics, and why it makes sense to practice new patterns of thought and behavior during that time.
He argues this measurement is more meaningful than the subjective questionnaires people usually rely on. He calls self-reporting unreliable and "not all that interesting," and compares Kernel to the blood glucose or cholesterol tracking already in Blueprint.
Jumping Over the Office Wall
Johnson described a behavioral change he noticed in the days after the session. Back at the office, walking with coworkers to a meeting, he came to a wall he estimates was about five feet tall. Instead of walking around it, he decided jumping over made more sense and did so without thinking. His coworkers asked what he was doing and said it was odd, and he agreed it probably was. He says he felt more open to different ideas, less "trapped," and that it felt liberating. Tolo, who picked him up after the session, said he seemed like a different person to be around for the next couple of days.
The Therapeutic Window and Integration
Mallin extended Johnson's airport analogy to trauma. A trauma pathway might be a habitual direct flight from San Francisco to New York. A healthier route, say through Seattle, might be hard to imagine. The drug opens more nodes so that new routes can form and the brain can bypass the ruts associated with depression or PTSD.
He tied this to "integration," the work that follows a psychedelic experience. During the window afterward, people can continue working on whatever they are trying to change and are more likely to succeed. For psychedelic-assisted therapy, he said, much of the therapy should happen then. His image is wet cement: right after the experience the brain can be molded, but after some number of days, depending on the drug, neuronal plasticity declines and new connections are harder to form.
Mallin mentioned a study he had seen correlating a drug's acute duration with the length of its therapeutic window. As he recalled it, ketamine's window was a few days, consistent with Johnson's Kernel data. MDMA's was about a week, and LSD's, whose effects last about 12 hours, was somewhat longer. Ibogaine, which can last up to 72 hours, was associated with a window of months.
Extending the Window: A Mouse Study and Proposed Experiments
Johnson asked about a paper the team found while preparing the episode. Mallin said researchers boosted the ERK signaling pathway in mice by combining ketamine with a drug called BCI, which inhibits DUSP6. This raised ERK activity and reinforced neural connections in the hippocampus, which he described as the memory center. The mice showed stronger neuronal connections and antidepressant-like behavior lasting eight weeks, compared with what he called ketamine's typical window of around a week or less. Mallin said he is not aware of this combination being used clinically but thinks it could be explored, especially if psychedelics gain clinical acceptance, which he believes the research supports. Johnson later stressed that this was animal research, not human research.
Johnson proposed a follow-up experiment: ketamine with BCI, measured on Kernel, to see whether the window can be extended. He also wanted to know what could be done within the window and measured. Mallin suggested learning, since opening plasticity windows has been shown to help learning in general, not just trauma. Johnson could learn a new language or instrument, or take memory and cognitive tests during the window and compare the results with performance before it opens or after it closes. Mallin admitted he was not sure how they would set up controls.
Johnson noted that ketamine could be done in the US, but ibogaine would likely require travel to South America or Mexico. Mallin mentioned a popular clinic in Tijuana that has worked with military veterans. He said ibogaine personally scares him a little because of its 72-hour duration. He cited Stanford studies in veterans with PTSD and brain injury or post-concussive syndrome, which he said showed roughly 85 to 90 percent remission of complex PTSD. For comparison, he put remission from SSRIs plus therapy for ordinary PTSD at about 30 percent. He framed it as a single intervention roughly tripling the best current outcome, and said results like this are unheard of in the pharmaceutical industry.
What Can Be Measured
Johnson asked what else a thorough panel might include alongside Kernel and wearable data, such as mitochondrial function or methylation changes. Mallin said this is difficult. The most interesting effects happen in the brain, which is hard to measure. Psychedelic research mostly relies on either surveys of subjective experience or expensive fMRI studies of activity such as glucose uptake in particular brain regions. He does not expect many easily measured biochemical changes in the blood. He thought it might be interesting to check whether brain inflammation rises temporarily after a psychedelic and mentioned a specific marker for this, but he said he did not know and the area is poorly studied. His suggestion was to start with the standard Blueprint panel of inflammatory and methylation markers, while expecting most of the action to stay hidden in neurochemical pathways rather than show up systemically.
Johnson argued that psychedelics have a "halo effect": people see them as protagonists in society and see cocaine and heroin as antagonists, but even supporters often do not understand the specifics. He thinks more data, such as what to do during the window and what happens in the body, could help people understand why they are using these substances and approach the experience with a clearer purpose. Mallin connected this to longevity. Many people using psychedelics for personal growth rather than illness, he said, want the energy to overcome the inertia of personal change, and the therapeutic window could provide that initial push toward the behavior changes longevity requires. Tolo said she would like to run the experiment systematically in a therapeutic setting, perhaps in Mexico.
Addiction, Bladder Damage, and Dose
Johnson asked whether ketamine's reputation for addiction and bladder problems is accurate. Mallin said it is somewhat exaggerated but has a basis. He explained that ketamine differs from classical psychedelics because it acts on the NMDA receptor, while DMT, LSD, psilocybin, 5-MeO-DMT, and to some extent MDMA act on the serotonin 2A receptor (MDMA also affects dopamine). With classical psychedelics, repeated use quickly stops working: psilocybin taken two days after a previous dose would produce a very small effect. Ketamine can be taken hour after hour with roughly the same response, which gives it more abuse potential. He called it minimally addictive and more psychologically than physically so, though he dislikes that distinction because "addiction is addiction." He confirmed that interstitial cystitis-type bladder problems have been reported with very frequent use. At therapeutic doses for the conditions discussed, he called ketamine extremely safe.
Tolo asked about the range of ketamine experiences. Mallin described a spectrum. At the low end is a "psycholytic" dose, where a person barely feels anything beyond a bit more openness, often used for psychedelic-assisted therapy alongside a conversation with a therapist. At the high end, at an IV infusion clinic, a person can enter the "K-hole," where they may barely remember anything or have an out-of-body experience with geometric visuals, sometimes coming out feeling they met God or watched themselves from across the room. As an anesthetic in a hospital, patients are usually fully knocked out and typically given other drugs as well, so they feel as if they went under and woke up. At very high doses, he said, people may remember nothing.
Where the Hosts Landed
Johnson summarized three conclusions. First, cocaine is not a longevity therapy and will substantially shorten life. Second, people should have a "Don't Die" drug kit with fentanyl test strips and naloxone nasal spray, especially since fentanyl poisoning is described as the leading cause of death for young adults. Third, ketamine looks promising based on research and his own Kernel data. The hosts point to its effects on PTSD and depression and its ability to open a therapeutic window, and to animal research suggesting the window might be extended.
The open question is whether they can test this themselves. Johnson said the episode invites the team to design a protocol that quantifies ketamine's effects on the brain, tries to extend the window, and measures plasticity through learning something new. When the episode ended, that experiment was a plan and had not been carried out.
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't think about it, and my co-workers were like, "Bryan, 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 for...
Except for the last one. Yeah.
This is anilingus. This is aka known as [ __ ], where someone uses their mouth, their tongue, their lips to stimulate someone else's anus for sexual pleasure.
Yeah, anilingus 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 anilingus? Is that a topic that you would 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 [ __ ]?
So, the assumption is they rim and the question is, do they enjoy it or not?
Yep. I mean, I feel like that's 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...
Decided it was 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 rimming?
I don't think I would. I don't have the urge to know. I'm not sure if I want to know. I mean, if you do know something like that, then do you avoid sharing like a cocktail, or, I mean, 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 part... We should have talked about that on the anilingus episode.
Yeah. I used to be much more casual about that, that I would, you know, 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. I mean, Kate, you can bring up rim. Mike can't. I would feel the same as Mike. I would have found it to be a pretty hard entry point to bring that topic up. On what we're talking about today with drugs, I would say it's probably more acceptable to inquire if somebody has used a given drug. You know, 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 I recount 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 like 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? 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 Bryan mentioned, I think people are a little less willing to talk about like coke, meth, heroin, things like that. But psychedelics seem 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 friendship bridge that, hey, we're part of the same tribe. We've had a similar experience. We can speak a similar language and share. And then if you haven't, yeah, there's maybe a question of why. But I would say that in the past few years, and probably because of the efforts that have been underway in getting the various, like psilocybin and MDMA, assessed for their therapeutic properties in depression, PTSD. So the normalization and the clinical blessing going through the FDA path, even though they've had a difficult time doing that, it's conferred a bit more credibility and status. I mean, I remember Kate and I went to a health gathering in Texas and there was a gentleman there who was like a world-renowned chemist or something like that, but, you know, he was in a 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, on stage with a big crowd, 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 your circles are a bit more progressive when it comes to these things too. Like you, 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 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 made the following sound, like ChatGPT. And I thought, does he realize that he's mimicking how ChatGPT is behaving? Now, maybe, because I've known this guy for a long time and he has never made that noise. 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 potent... I guess let's say drugs as a category, which include 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 aware of it. This has been an area, just a topic of interest for me for a long time. So I also was like PI on one of the studies that we're talking about with longevity. So yeah, super aware of the potential benefit, especially around like the mental health aspect of these medications. So yeah, I'm super excited to talk about this. I think this is going to be a cool topic that has been talked about a lot 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 is 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 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. 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 Bryan Johnson at 47 after microcalibrating 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: what properties of health and longevity do these various psychedelics have, and then conversely we will talk about drugs such as cocaine, heroin and others and the potential risks that they face.
Can we take a minute and appreciate the quality of that trolling? I mean, it's upper level trolling, right?
This is always "yes, and," never "no, but." Just, you know, when somebody pokes fun of you, the best move is always to "yes, and," play along. Be the butt of the joke. You know, have a good laugh at yourself and, you know, maybe it will lead you to good outcomes. Maybe we're going to find that ketamine and blow 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 can cocaine have on somebody?
Yeah, cocaine is 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 increased by about 4 to 8 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. 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 is equivalent to about 10.8 years of life lost on average. So I think like cocaine is clear. It's bad news. And there's no longevity benefit.
That's wild. That's such a significant amount of life lost. I...
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 I mean, it is very activating, right? So it is a stimulant, and stimulants in general 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 are causing pretty significant challenges to the homeostasis of your body and are 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 modafinil works in terms of keeping you awake. It's not a stimulant 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 blow in the protocol, it sounds like. Is there any benefit to cocaine that we're aware of besides central in-the-moment joy?
Stop a nosebleed. It's great. It's like one of the best drugs you can use to stop it. I mean, seriously. So like in the emergency department, we would sometimes, in people who had really bad nosebleeds, actually like shoot some cocaine. Very small amounts compared to what people like for fun.
So you kept cocaine in the hospital?
Yeah, we had cocaine 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 doctors are stealing that and doing that.
I don't think so. It's actually really hard to steal. The processes are pretty good in most hospitals about getting those controlled substances. So 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 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 a liquid, basically. Yeah. To shoot it into somebody's nose.
Oh, okay. Oh, as a spray.
Wow. Okay. Fascinating. Who would have known?
I still don't... It's not like the... You're not doing... You're not like making a line for the patient, right? Yeah. All right.
And also, like, 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 waiting to happen. You're like, the doctor's punching the patient in the face. It's like, you know, behind the curtain. It's like, this patient needs some coke. Nurse, grab that. And then, you know, there's no way there's cocaine being held in the hospital and people are not working in tandem to abuse it. 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, this is definitely a tangent, but 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, one of the best ways to prevent withdrawal is for them actually to drink, and you don't want them to withdraw 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 prescribe cocaine, a can of beer, like yeah, there's all kinds of stuff in there.
Wow. And there's no drug to act like alcohol without being alcohol to
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 topic of emergency drug situations, fentanyl is in a lot of our 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 another thing. First off, I'm not sure I can give anybody a protocol for doing cocaine. I think our protocol for doing cocaine should be you should not do cocaine, but 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 like, I mean 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 pills. It's happening with cocaine, all kinds of stuff where we're seeing fentanyl. The problem with fentanyl is per gram it is extreme. It is like 100 times stronger than a standard other drug. So a very, very small amount of it in your pill is enough to kill you. And what we're seeing is about 100% increase in fentanyl-related deaths year-over-year in 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. You can go online and for like 15 bucks, buy two doses of nasal naloxone spray. And that should be on hand for you, for your friends. In my opinion, pretty much everyone should have it 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 beyond just having that rescue drug available, you can also purchase fentanyl test strips where you take a little tiny piece of the pill or the drug or whatever you've purchased and 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 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 fentanyl overdose. And this is, I think, an underappreciated problem in our society today and something that we should be very clear about. And talking about this particular topic today, I think, 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 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.
Michael, would it be a good idea, 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, 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, I think this is something everyone should be acquainted with. We should not have any hesitation talking about this. 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 looked this up. 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 US.
True.
Wait, we're talking about longevity, and the cohort of people that aren't susceptible to 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? 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? 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 opiates on a regular basis. But if they're unresponsive, 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 it only acts on opioid receptors, so you're not going to cause anything else. Without a doubt, somebody's unresponsive, while you're checking their pulse, you should be shooting this up their nose.
Okay. So unresponsive. They've got a pulse. I mean, obviously call an ambulance
100%. Yeah. All the basic stuff. This is an intervention that could potentially save their life while you're doing all the call 911, check for a 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-risk drug. Well, that was a really important detour. I'm glad we covered that, because I'm absolutely inspired now. I will get a keychain version. So thanks, Mike. Okay, so blow 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 is interesting. Ketamine is a drug I'm extremely familiar with. We use it a lot in medicine as basically an anesthetic. So, we're 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 are 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 interested.
But there's been also a study on ketamine specifically for longevity, which is actually a study I was involved in performing. We had 20 patients with depression who got six ketamine infusions. So they went to an IV ketamine clinic, got these six infusions, and 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 PhenoAge decreased by 2 years, GrimAge by 1.1 years, OMICmAge by one year, their brain age by 1.5 years lower, inflammation down by two, metabolic down by three. So across the board we were seeing people actually appearing to be not just mentally healthier but also physically healthier, and a reduction in their biological age, which was I think super interesting. And mechanistically it doesn't necessarily make a lot of sense unless you believe that there is this sort of body-brain connection, right? You improve the brain, the body follows along with it; you improve the body, the brain follows along with it, which I tend to believe in. But there's not clear mechanistic examples yet.
Mike, we were just 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 is that it's changing the depression. So all of these people had significant reductions in their self-reported depression and PTSD symptoms. And my guess is that they are making... I mean, you think about 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 that improvement that you've had mentally. So my guess is this is all secondary. I mean, there's no way to know whether this is truly causal or not. There's 20 patients and it wasn't 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 participants, which is my guess.
It's fascinating that ketamine has such an impact on the brain, because Bryan, we literally studied this at Kernel. 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 Kernel. We were trying to enable what happens when, and our entire life is built around these basic hypotheses, 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 uses a technology called time-domain functional near-infrared spectroscopy. It's basically like 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. Do you see that before ketamine on days 1 through 5, 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 2, 3, 4 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 psychedelics and it opens the mind up to new ideas.
And so the way to think about this is that your brain has nodes, networks of communication. And so think of it like planet Earth with airports, and planes are flying from node to node, 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 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 cuz
You did this annoyingly.
You wind up for me.
Well, just asking me. I'm just walking down the
No, he's going to finish that sentence. But I'm laughing so much cuz I remember coming to pick you up, Bryan. And it's funny, these experiences, and you were so different those next couple days. You were just like, yeah, a different human to interact with.
Yeah, we were at the office. So 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, probably like a 5ft wall, a pretty size of a 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 co-workers were like, "Bryan, what are you doing? That is really odd." And I thought, "Oh, you're right. I guess that might be a little odd." But 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 effects of my brain activity for the first five 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 in Blueprint, whether it be blood glucose or cholesterol or anything else. Now we have Kernel to measure this high-fidelity brain activity. So that was cool to see, where otherwise people just talk about it in a subjective way. They take questionnaires and say I feel this way, but subjective reporting is really unreliable and not all that interesting.
I like the way you describe it too, like 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. Let's take for example a trauma scenario, right? So you've got a flight from San Francisco to New York, that's your trauma connection in your brain, right? And if you're so used to taking that one flight, it's hard for you to imagine going from San Francisco to Seattle to New York, right? But maybe the San Francisco to Seattle to New York is the non-trauma pathway, right? So it's like taking this medicine opens up all these additional nodes so that you can create new pathways and bypass these ruts that the brain gets in when it comes to mental health, right? So it's just really interesting to think about it 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 a few days, as you saw with Kernel. But some of the longer acting ones, like ibogaine, which lasts for upwards of 72 hours, was months. Your therapeutic window is open for months. MDMA was, I think, around a week, LSD slightly longer because it's a 12-hour duration. But it was really interesting, the duration of the psychedelic was associated with the duration of the opening window afterwards.
Wow. That's really interesting. So can you actually explain the therapy window? Is that when you want to intervene to kind of try to, like, yeah, 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 relive an old life or you meet these architectural creatures or whatever happens, some stuff happens. After that, in 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 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 its old ways, but it kind of hardens. Imagine wet cement, right? Right after the psychedelic experience you've kind of got wet cement. You can mold things how you want, 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 the 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 paper on 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 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 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 8 weeks, as opposed to what we typically consider the duration for ketamine, which is 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 is something that I think we could look at in the future, especially if we start to see psychedelics come more into clinical acceptance as tools, which they should based on the research we're seeing.
Yeah. I'm just 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. 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.
Like 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. I'm not sure how we control for it, but one thing that plasticity has been shown, opening these plasticity windows has been shown to be beneficial not just for mental health benefit, like retraining trauma pathways, but also just for learning in general. So we could do different types of learning or learning tests, memory and 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 ketamine here in the States. The ibogaine, we would probably need to travel to South America.
Or Mexico. Yeah. There is, not too far from you, a pretty popular clinic in Tijuana that's done some amazing work in war vets. So ibogaine is interesting, 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 85 to 90% remission of complex PTSD. Just to put that, that sounds cool, yeah, 90% remission, but just to put that into context, the remission rate from SSRI plus therapy for PTSD, not even complex PTSD, is like 30%. So the best medicine has to offer right now is 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, you don't hear about this stuff in the pharmaceutical industry. This is crazy.
What else could we measure? So if we did neuro effects with Kernel, we'd have all the wearable data. Would we look at mitochondrial function, methylation changes? What else would we look at for a comprehensive panel of what effects, what are the things happening in the body when you do something like ibogaine?
This also gets to your brain-body connection, Mike.
Yeah, this is tough. I mean, we're talking about things where the predominant pathways that are interesting and beneficial are happening in the brain. The brain is inherently hard to measure, right? Which is why Kernel is so interesting, but it's challenging to measure these pathways. So you look at these studies on psychedelics, they're predominantly fMRI, or either they're like, let's give them a survey and ask them questions about how they feel, or they're super expensive, complicated fMRI studies where they're looking at glucose uptake in certain brain regions, because the brain is inherently hard to measure. So we're kind of stuck with, we're either surveying your subjective experience or we're actually visually looking at the brain. Beyond that, there's not a lot of biochemical changes that are going to be easy to measure. It'd be interesting to look at SMB, right? That would be super interesting, looking and seeing is there a change in inflammation, because there might be a temporary increase in brain inflammation after psychedelics. I'm not sure, to be honest. This stuff isn't well studied. So there's a wealth of opportunity here. We could start with the basic panel that we do for you, with all of our inflammatory markers and looking at all of our methylation 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 neurochemical pathways rather than things that we see systemically.
Kate, what do you think? 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 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 phenomenon of what happens when...
And I think most people give psychedelics the benefit of the doubt
because they kind of have a halo effect where they're viewed as, you know, 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 nuanced effects of them. So I think this would be really helpful. 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 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, 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? In so many ways, this is kind of like the potential for a key to behavior change, right? I mean, ultimately that's what a lot of people's goals are. I mean, obviously some people are coming forward for depression, for PTSD, for these true diseases that they need help with, but there are other people who are using psychedelics for just personal growth, and in a lot of ways I think what those people are looking for is, I want to say, motivation, the energy to overcome the inertia of personal change. And that therapeutic window can be the opening and 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. Just to take a step back, ketamine is very different than the classical psychedelics. It's working on the 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 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 psychologically addictive than it is truly physically addictive, right? I don't really like making those differences because addiction is addiction. But it does have more abuse potential as opposed to the classical psychedelics, where if you keep hitting that serotonin receptor, it just stops working. Not forever, but if you did psilocybin and then 2 days later did psilocybin again, the second experience would be extremely minimal because all those receptors are kind of like, I've seen this, I'm not doing that again. Whereas ketamine, you could do it hour after hour and pretty much get the same response over time. So it's a little bit more addictive. There have been reports, with extremely regular use, of these interstitial cystitis bladder-type issues, reported for sure. But 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 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 in the 1960s we first started using it in the medical setting for anesthesia, specifically for folks that can't take typical anesthetics, right? Is that right?
Yes. I mean, but now to the point where it's used preferentially because it's so safe as opposed to a lot of anesthetics. So, you know, 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, 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 lighter experience. Is there a better therapeutic place to be or do they all have benefits?
So you can go as low as, you know, a just 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 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 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 out-of-body experience and you see a lot of geometric shapes and come out of it feeling like you met God or 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 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 just feel kind of knocked out and you wake up later.
But yeah, it can go all the way to
like you don't remember anything if you take really high doses of it.
All right, 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 the 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 therapeutic 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 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 [ __ ] 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 your brazen assumption that they rim that you didn't even inquire. Do you It was like your question was do you enjoy [ __ ] It was not like do you rim. So the assumption is embedded in that.
Well, cuz 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 do enjoy." So, they have to make just one baby step versus two.
Right. Exactly.
Kate, 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 expect anything less?
We'll see. We'll see what they say.
Okay. Until next time, friends. Be well. This is the Bryan Johnson podcast. Special thanks to my co-hosts Kate Tolo and Dr. Mike Mallin. 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, Bryan
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