Psilocybin, LSD & Marijuana: Ranking Drugs for Longevity (Part 2)

I was recently with Snoop Dogg. He was high, as one may expect, when I was talking to him. So I'm not quite sure how much he heard what I was saying.

So I'm sure he heard everything you were saying. Like at this point he probably thinks better when he's smoking than when he's.

Not, I would assume.

We want to know, Brian, did you smoke with Snoop Dogg?

There was a study that said that demonstrated shrooms may have some anti aging benefits which got people pretty excited.

We don't really know for sure, but at least in mice there is some preliminary data that suggests that psilocybin could have a longevity benefit that may be mechanistic outside of just making you happier and less anxious and less depressed.

Lsd, we have a study here, it was given to worms and extended lifespan.

Yeah, so we saw an increase in lifespan by about 25% in these worms. So there was a group of worms who got lsd, a group of worms who did not. But you're not a worm.

What is your, your conscious experience like.

As a worm, let alone a worm on lsd?

Yeah. And like you're doing your thing and you stumble upon this psychedelic. You don't know how to anticipate that this is coming on. It starts happening to you. You don't even know what is going on. Complete discombobulation. You're not quite sure how to replicate that experience.

Do you think a worm also thinks that they're one with the universe?

Hi friends. Today we are talking about shrooms, also known as psilocybin. We are also going to talk about lsd, DMT and marijuana. And we're going to talk about some evidence that has recently been published on the potential longevity properties of the psychedelic molecules. And we're also going to talk about how you can be mindful to be safe when doing these things. It is of course always good to be in touch with your medical professional and also to be aware of the risks. So let's get into it. Do you remember the first time that you were offered drugs or around somebody who was doing drugs?

Yeah.

How old were you? Thirteen. Oh no. What, what was the drug?

Marijuana.

You know what they say about marijuana being the gateway drug? It actually is, not in like a negative way, but it definitely like my first exposure to drugs was marijuana too.

What happened in those circumstances? Who had it? You offered it, what did you feel?

It was my best friend who I think got it from his parents, if I'm not mistaken. Like, I don't think they knew that, but like, yeah, that's where he. That's where he got it from. And it was like at that point, probably the single most euphoric experience I had ever had up until that time. Yeah, it was like. It was. I can see why people get so attracted to. To drugs based on the feeling, for sure.

At the age 13, I can imagine being transported into a marijuana induced high.

Yeah, I can.

Was it in a pipe?

No, it was a bong.

Kate, what was yours?

I just remember being offered around that age, like 14, maybe. Ish. Same situation. Best friend, her mom had weed around the house and I think her mom was really chill about it. She was just like, here, here, if you want. If you want it, like, it's fine. Like, go for it. So, yeah, it was that kind of situation. I grew up in a household where weed was the devil. Like, you do not. You do not mess with marijuana. That was like. And the reason was because I have schizophrenia in my. Both sides of my family background. And so my mom was really concerned about it. I don't even know if that scientifically holds up.

Unclear if it's actually causing schizophrenia. Likely not. It's likely. Just precipitating the first psychotic event is more likely. But I don't think we truly understand, to be honest.

Do you know if there's any indication on whether or not it can evoke it when someone isn't going to get it typically in their life?

I don't know, but I don't think so. Yeah, we could look into that. It'd be interesting to evaluate.

Brian, what about you?

Yeah.

And important context for the listener here is that Brian grew up Mormon in a very woman community in Utah, like U2.

It was my best friend. We were in the parking lot of Albertsons. He was in his dad's little yellow truck and he pulled out a Coke can that he then in front of me, made this smoking apparatus where you crush the middle, you poke holes in the middle and you then you pull the weed and he pulls it out like he's a pro. Builds this thing, puts it on top, lights it up, and then he says, do you want some? Like, what are you doing, man? When did you start this? What is this? I'd never seen it. I'd never smelled it. I had no idea what was happening. I didn't dare do it in that moment. But it was such a shocking experience. And he just was this. I think he was 15. It's like we. None of us had our driver's licenses, but we all just kind of took our parents Cars and would just drive around. It was kind of like a lawless little town. I just couldn't bring myself to do it. It was too much. He had a good time with it. Like, he. Over the years, he just became a pro and it was part of his mainstay.

So that you were 15.

Yeah.

When was the first time you tried drugs?

Ketamine was one of the first times I did anything.

Well, that's some. That's some intro.

Yeah. A 60. Almost a 60 milligram dose intramuscular dose of ketamine.

Those hit the hardest too. The. The intramuscular as opp. Like IV ramps up slowly. Oral is a slow ramp. IM is like bam. It's too tough. It's you real quick.

Yeah. I mean, given that it. I got into my early 30s before I did anything like that, it makes me wonder what society would be like if. So I guess like one is there's no true way a society is formed. There's been thousands of versions of how society creates ethical and social norms. We are in a version, but there's no truth to our version. It's just a version that we've chosen. I wonder if there's a. A version of society where psychedelics are actively introduced as part of culture as you hit certain ages and people go through journeys to. Through structured journeys to experience development and trauma processing. That is just part of our norms, I think. I mean, a lot of societies have.

Some different cultures doing this for a long time. Right. I mean, like, lots of ancestral cultures have, like peyote, for example, and know Native American culture, indigenous. Indigenous cultures. Like, lots of cultures have done this where there's this. The hero's journey that. That a child goes off on prior to becoming an adult.

Yeah. I wonder how much it would change people, you know, in. In terms of, like, what. How we see each other in the world and how we understand reality and specifically is all. If it was done in. With all the robustness of the ways we can measure things.

You know, this is like a pretty big tangent, but it does feel like our society as it currently is structured lends itself to a lack of freedom that psychedelics, you know, from a personal standpoint, they give you a play space within your own brain that you didn't necessarily know that you had before you took them. I think it's interesting. It's like it creates elbow room within your own perception of your own consciousness. And so it's interesting that it does feel like so much of the linear path that our current society goes down with Age ends up getting smaller and smaller play space that you get to play with. I think there's probably some sort of interesting third there with longevity and youthfulness speaking to a lot more play space than we're afforded later in life. Yeah, I think it's something interesting to be said that there's a link here with longevity that as we get older, we get less and less play space. And with youth, we're given more liberties and how we can think about ourselves and what we can try and boundaries we can push on.

Yeah, we. Our culture is so, so egocentric in so many ways. It's so like human focused and individual focused. It'd be interesting to see how. How specifically Western culture would respond to what you're describing, Brian, with more of. Like a. More of a expansive idea of self and purpose that is beyond just the individual person.

Yeah. In our last discussion around psychedelics, it had me thinking about. We did five Don't Die summits, gathering a thousand plus people and approaching new ideas about how to be through education and community and activity and learning about longevity therapies. I wonder if there's a version that we. We did psychedelic experiences where when you fully sit into Don't Die and you really adopt that you. You try to fully comprehend what we're saying. This is a form of existence, of valuing existence beyond our ability to comprehend right now. And it's so hard to do it in motion within when you're in the system of running and grinding hard. And I wonder if psychedelics would create the space to actually sink into it. So imagine we did these Don't Die dinners in some kind of altered state where, I mean. Kate, no, hang with me, Kate. I'm watching your body language. Hang. Hang with me. Don't go. Don't wait. Hold tight.

Consult your lawyer, Brian.

Yeah, I do. But wait, go what?

Isn't it interesting that, like, it just veers toward cult land? That's like the, the quintessentials, like groups, small groups take LSD and like microdose it and then have these experiences. It's just funny. It's just funny. It makes sense. So you know what I mean?

Yeah, I do. But I do wonder if. Because I guess in watching people struggle with the competing forces of their life, I wonder if they. If they had a bit more space to process this. And when we do these dinners and we give people two to two and a half hours and they get time to relax and, you know, like, find room to like, really explore new concepts, they do arrive there in the two hour timeframe. But you know, the moment they leave and the phone dings, they're out like they're back in the world and it's just very hard. Yeah, I just guess I was left thinking about that after our last conversation of the enduring effects and the openness that we would have. Because otherwise it's pretty hard to wrap your head around a brand new ideology that just changes your. Your understanding of reality.

Yeah.

Okay. On that topic. Yes, Kate, you have something else?

No.

I think you do.

I did and then I have. I just cataloged it out and so now I moved on.

Uncatalog it, bring it back out. What was it?

Oh, it was about death cope that, you know, we're talking about longevity. And I think at a very early age we learn that we will die. And it's a very terrifying thought and a lot of people never unpack that again. And so I could imagine actually almost like a psychedelic therapy around the idea of death and our relationship with it. Because I think a lot of the vitriol and hate that we receive in the world is actually this instinctual kick up around. Hey, you guys, I don't want to think about my death. I don't want to talk about it. I don't want to see the numbers, I don't want to see the data. I don't want to find out if I have cancer right now. I just want to ignore it. And so there's something interesting there too.

Kate, what do you think about this? Should we kick this thing up?

Kick what up? The experience.

Yeah, the don't die psychedelic trip. Oh, you don't like it, you don't like it. You just see problems.

It would be a path that we would have to commit to. I'm definitely interested in going to Mexico.

I'll do it at least a first go chronicling this, doing this, measuring it and seeing what we find out.

Just go to Colorado. You don't need to go to Mexico. Yeah, Colorado legalized basically for therapeutic, well, all medicinal plants. So any, anything that you can get from a plant you can now take in Colorado.

What? Wow, let's see. Ibogaine. Is that a plant?

That's plant.

Okay. I don't know if I go to.

Colorado for that, though. I'm not sure. I don't know of anyone doing that with a lot of experience in Colorado. And I would want to do a lot of research into who I did that with. There's a lot, there's a lot to think about that things. Some things we haven't gone over like, there's a lot of talk of like cardiac arrhythmias with ibogaine, especially with people who have something called prolonged QT syndrome. So you can just have a cardiac arrest in the middle of it if you're not appropriately screened and if they don't have the right medications there to prevent you from getting dehydrated and your magnesium level getting too low. So ibogaine's a little bit scary.

Yeah. I'm guessing that they do not have that robustness of, of assessment going into these, these sessions.

Some do, some do like, some of the, some of these clinics are doing a really good job, but majority of them I don't think, I don't think are doing it.

Yeah, I'm saying like, generally speaking where, like when I hear people, it's like, oh my shaman.

But yeah, like your shaman doesn't, is not, is not doing any medical assessment. They're, you know, they're, they're listening to the plant.

They're like, yeah, that's right.

The plant told me you need this.

That's right.

This dose. Yeah.

For those of you who didn't here the previous episode, we, last time we spoke about cocaine and how it's not a longevity drug, we dipped into ketamine, about the potential positive effects of ketamine and how we are now trying to think through our own protocol for doing ketamine and extending its therapeutic window, then assessing how plastic is the brain. We have kernel to measure it. And today we're going to jump into shrooms because this was kicked off a while back where a few weeks ago there was a study that said that demonstrated shrooms may have some anti aging benefits, which got people pretty excited. In fact, one of my friends who has been scoring really well on his speed of aging, looking at this pace methylation clock does a lot of mushrooms, but yet he also doesn't go to bed on time and he doesn't maintain the best health habits. And we have been trying to figure out why is he doing so well on his speed of aging. And he was hypothesizing maybe it's his, his reliable consumption of mushrooms. Mike, what can you level set us? What did this paper demonstrate and why is it intriguing to investigate further?

Yeah, so there's been a few studies on psilocybin looking specifically at, at longevity. And what's interesting is, you know, there's, there's been a lot of research looking at the health, the mental health benefits and actually something you were talking about earlier, Kate, talking about how wouldn't it be interesting if we could use this for death cope? Some of the first studies done at John Hopkins University were actually in people who had terminal cancer diagnoses, and they found a significant reduction in depression and anxiety symptoms associated with death with a single dose of psilocybin, which is pretty impressive. But it looks like, at least in a few studies, that the benefits go beyond what we would expect from mental health around depression, ptsd, anxiety, the things we typically think about with these psychedelics, and that is that psilocybin is actually helping cells stay younger by actually prolonging telomeres, which is, you know, that protective piece of your chromosome. And it appears that, at least in. In mice. For example, in a study that was done in older mice, giving a monthly dose of psilocybin led to a longer lifespan. So after about 10 months, 80% of treated mice were still alive, compared to just 50% of untreated mice. So that means 30%, basically, improvement in longevity in those older mice who got a monthly dose of psilocybin. And we don't really know exactly why this is happening. It, you know, psilocybin's hitting that, that 5ht receptor, the serotonin receptor, and it could be that it's actually activating SIRT mechanisms and improving DNA repair as well as telomere elongation. We don't really know for sure, but at least in mice, there is some preliminary data that suggests that psilocybin could have a longevity benefit that may be mechanistic outside of just making you happier and less anxious and less depressed, which is kind of interesting.

Are we considering a psilocybin protocol for Brian?

I think we would need to get IRB approval for this. Is that correct? Because this, See, I guess this is legal in Colorado. Is it also legal in Oregon, but it's not legal in California?

Oregon, Oregon and Colorado are the two places where there is medical use of psilocybin.

I would need to travel to these states, do the dose.

Yep. Yeah. Or in an irb in a different. In a different state. Yeah.

And for those of you not familiar with an irb, it's basically an ethics review board that approves the study design to make sure it's safe and, you know, has the appropriate controls in place. Yeah. Mike, what. What do you think? Based upon this study, of course, it. They. We're not looking at different protocols. They were just looking at the introduction of psilocybin. What do you think the protocol would be if we tried this out? What would we experiment with, you know.

I guess we would probably mimic something like we did with the ketamine study, where we'd look at epigenetic biological age pre and post. But according to this, we'd also look at telomeres. We could even look at like cellular NAD levels if there is this potential activation of SIRT and this potential NAD activation. Be interesting to see if, like, does just taking psilocybin increase your intracellular NAD levels? Does it, does it activate that pathway? That would be interesting as well. So we, we probably do some of the similar tests that we typically do, but try to hone in a little bit closer to cellular senescence and cellular aging mechanisms.

One of the challenges we would have is that, for example, in, when we were, when we were evaluating hbot, we saw that in the participants that were primarily aged 65 and older, I think they saw something like a 20 increase in telomere length. Whereas in my telomeres, because I'm already in the eight, we use Spectracell, they've got a data set of 15,000 samples. And in that data set, my length of my telomeres was age 10 to 15. So already extremely young biologically. So in HBOT, to finish that thought, I think my increase was something like 1% or 2%. It was some small increase or maybe it just offset the decline I would have predictably in a given year, but within that it was pretty minimal. I wonder if this would have a larger effect or if we'd see something similar where it increases because this, this was given to older mice. Right? Sim. Similar with the HBOT study.

Yeah. The ketamine study that we talked about last time was given to people with PC, PTSD and depression. So you are not, you're not high risk category in either of those studies. Right. So like you're, you're not the same participant group as either one of those. You're not an old mouse and you don't have depression and ptsd. So it's hard to say that we would see a measurable change with you.

So yeah, Ally just confirmed it was around 2%. So 3 kilobase, 0.03 kilobase. So yeah, this is the thing that a lot of people, the headline is, you know, psilocybin is good for longevity, but understanding the nuance of, for whom and under what conditions is really important because it may not have the beneficial effect in a more youthful population. But still, I mean, interesting that it not only had the elongation of the telomeres, but also showed that cells behave differently that they divided more before becoming senesced.

Yeah, Very early research though. I mean, we talked about mice, we're talking about a small study and we don't really truly understand the mechanism. So this definitely falls into the preliminary research category for sure.

Yeah. Similarly, lsd, we have a study here that has the same kind of characteristics where it was given to worms and extended lifespan. What happened there, Mike?

Yeah, so we saw an increase in lifespan by about 25% in these worms. Um, so there was a group of worms who got lsd, a group of worms who did not. Um, and basically they found that the LSD kind of mimicked caloric restriction but for the worms, which is interesting and may play similarly to the same mechanisms we're theorizing with the psilocybin in the mice where this sort of cert activation, so sort of the. Which is, falls in that like caloric restriction category of kind of cellular. Cellular healing, basically. So 25% increase in life expectancy for worms, again interesting, but also falls in that category of you're not a worm. And we don't truly understand how or why this is working. So there's like, I think for me this is interesting and like cool to talk about at a party, but not a reason for me to design a protocol for you or for to change my behavior as a longevity interested human.

What is the cert? You mentioned that a couple of times. What is that cert?

It's like it's a part of your cell that helps repair DNA, like its job. There's lots of different certs, but the one we're talking about, its job is actually to repair DNA and make sure the DNA is coiled up appropriately. And then it's like doing everything that it's supposed to be doing. And it is commonly activated by a lot of the medications we think of as longevity medications and also by caloric restriction and a lot of the activities that we think about as being longevity activities like exercise, caloric restriction, sleep, all those things that we think about as being healthy.

There's gotta be a meme in here of some worms on lsd. We'll have one out by.

That's gonna be kind of fun. I could think about a lot of. Lot of cool things you can have. It's like some holographic thing going on on a worm with wearing like some pink sunglasses.

Okay, I'll say yes to that. I mean, okay, like I don't know. I mean, what is, what is your, your conscious experience like as a worm or a fish or like you know.

A plant, let alone a worm on lsd. Yeah, yeah.

And like you're doing your thing and you stumble upon this psychedelic and you have no, you don't know how to anticipate that this is coming on. It starts happening to you. You can't even. You don't even know what is going on. Complete discombobulation. You're not quite sure how to replicate that experience.

Do you think a worm also thinks that they're one with the universe? Is that their conclusion?

Probably.

I wonder in some duration of time if we will be able to probe consciousness and create models of what it's like. When I did ketamine as part of the kernel experiment, I. Before that, if somebody would have said to me, give me examples of what your conscious mind is capable of. Like, tell me, where can it go? What can you feel? What thoughts can you embrace? Like, what does it feel like to be a conscious being? If I would have been given an entire week of thought space with no other responsibilities, I would not have been able to imagine that. Right. And just, it's very practical. You are. You bump up against your own limitations of your experienced reality and you can't punch through that very easily. And so ketamine just like blew it open of like, my mind is really capable of this novel thing. And so I think the. When you list out what are the coolest things that we have in front of us right now, we have a fever pitch interest in asi. I'm not quite sure why. We equally don't have a similar ambition of like, what could our conscious experience be like? And psychedelics are the closest pathway for that. People saying psychonauts, you know, it's a cool thing to explore and, but it's just not really framed as an ambition. It's. It's kind of framed as this alt path, but not really viewed through a builder mindset.

So fascinating. Do we know Mike, who isn't the best fit for this kind of experience? Because obviously anecdotally we hear about bad trips and people having even psychotic breaks. Is it quantifiable? Can we figure that out?

It is a challenge for sure. So there are people who, you know, if you ask, if you ask a practitioner who should not partake in these, in these medications or these drugs, they would tell you people with psychosis. So often we think about bipolar disorder being a contraindication, schizophrenia being a contraindication, any history of psychotic break being a contraindication. So those are people that should avoid or make sure they are doing it with A practitioner who understands the extent of their, their psychological issues. Beyond that, something around 10% of trips are quote unquote bad trips. And yeah, it's hard to know what exactly a bad trip trip is other than just a negative subjective experience of the trip immediately during or immediately after the trip. The interesting thing is almost 100% of those, when asked some time after the experience, almost 100% of those of those experiences are actually thought to be positive. So people change their mind. So during the experience they have this negative experience, right? Like it's, maybe there's demons or black shadows or I don't know, I'm like making stuff up now. Maybe it's black elephants, but like, you know, whatever it is, there's some, some dark imagery or some, some, some negative experience that they, that they have that is initially anxiety provoking or challenging and then later on they sort of flip it and they realize why that happened, why was it negative, what were they trying to overcome, what was the, the deeper meaning to that experience and actually flip it and believe that it was actually a positive thing. So it's, when you even talk about bad trips or negative experiences, it's hard to know like, are they truly bad? And there's a saying like in the, in the psychonaut world, like no such thing as bad trips. And the, the point there being that like even the bad trips are teaching you something and it's just a matter of understanding what's trying to be told as opposed to going in and having a beautiful, wonderful experience. But once you get past the what, what are the, what's the positive feelings? Like, am I just here for positive feelings or am I here to grow? Like that's the, that's the speed bump people have to get over.

And also alcohol misuse. Is that right, Mike? Like folks that are alcohol dependent.

Yeah. An interesting story is that the, the guy who started Alcoholics Anonymous supposedly did lsd and that was a, that played a big part in his role in developing AA later on. But the, the studies on LSD have shown that there's about a, I think it's a 50% reduction or clearance of negative use of alcohol just with a single dose of lsd, similar with DMT as well. If I believe, if I remember correctly.

Brian, maybe your brain went here too. But we were talking about in the last episode using psychedelics to change behavioral things that get in the way of you being healthy, for example. And you can also imagine that death cope is almost like a Deathaholics Anonymous for society right now. Where We.

There we go.

Engage. And this goes back to your don't die summits and everyone doing psychedelics together, but that we engage in death related behaviors because we are trying to cope.

You found it, Kate. That's what I was trying to circle on. And you just identified it. I think that is the hypothesis I would go with is that people are addicted to death.

They misuse it. They misuse as a substance.

Yeah, it's exactly. It's a substance for. Through the, the framing of living your best life through pleasure frameworks.

Excuse to make bad decisions.

Yes, yeah, exactly. That it is as robust of an addiction and a distortion that. I mean if you basically size up death addiction to alcohol or any other form of addiction, food, porn, substance, that it's probably just as formidable psychologically, if not more so than the others because it's embedded so deeply you can't even see it.

Yolo. Right. I mean it's cultural. You only live once. These like excuses to make bad decisions, they are inherently regarding death.

Yeah, I'm. I'm here for a good time, not a long time. All these.

You sleeping dead.

That's right. All these simplistic statements that try to make sense of a complicated reality with some throwaway comment. I like this, you guys. I think we're making good progress on this. Brainstorming that this is. We haven't framed don't die, you know, through, through the lens of addiction recovery, but it's powerful.

DMT. Wait, Brian, is that what your tattoo is?

5Meo DMT.

What's the difference?

It's a different molecule.

Is there any like. Mike, is there any data to back up whether or not DMT can extend life or improve health? Does it do the opposite?

No, there's no, there's no data so far regarding longevity specifically with dmt. There is some. There's some data suggesting that it can do the similar things that the other psychedelics can do like improve cognition, neuroplasticity, help with depression, anxiety, things like that. But it nothing around like epigenetic data or anything we've seen with mice in, in LSD or, or psilocybin.

Sounds like shrooms is really promising. And then we're still waiting for data to come back on LSD and DMT as it relates to health and longevity. From a data driven standpoint.

My guess is that it's likely that all of. If there is a longevity benefit from these traditional psychedelics, it's likely all of them because they all act kind of in the same way in the sense that they're hitting the same receptor. It would only make sense that they're, if they're hitting that same receptor, they're going to have very similar outcomes on longevity. So I think if we prove that like one of these has, has a significant longevity benefit, it's likely that it's consistent between shrooms between LSD, between DMT 5 Meo, DMT I, I began all the, all the traditional psychedelics.

Is there anything to support that Shrooms has some sort of added benefit because it's a natural compound versus LSD that's synthetic or is that like a myth within society?

There hasn't been really a, like a strong head to head blind control, you know, controlled trial here. Theoretically they're, they're extremely similar in terms of their molecule shape, where they work, the mechanism of action. The differences really are just like duration of action. You will note that like there's slight differences in the actual effect. Like LSD is what much typically much more visual, hits the visual cortex a lot more. Whereas Shrooms are a little bit more like nature type imagery and connecting with mother nature kind of, kind of situation. So there is like some subjective differences but like neurochemically extremely similar. I hesitate to say that like one is safer than the other or better than the other in any way. Like there, there are studies on both that have proven, you know, significantly better outcomes when it comes to depression, anxiety and ptsd. And then LSD has those studies on, on addiction recovery. But psilocybin is also used in addiction recovery as well. So very similar in my mind.

So my summary on this is Mike, we do want to do a ketamine protocol to evaluate its anti aging effects and the therapeutic window and the elongation. We also want to do a psilocybin protocol and we want to, to assess whether it can elongate my telomeres which are already in a good spot. We need to figure out the dosing protocol and then we need to figure out where to do it either in Colorado or Oregon and frequency dose. And then we can do brains, we can look at telomeres and brain. What else would we measure on the psilocybin protocol as endpoints?

Well, we talked about using the kernel, I think that's really interesting for both ketamine and for, for psilocybin. We talked about measuring the telomere length, epigenetic age and it sounds like intercellular nad could be interesting as well based on that, that one mouse study that we saw. So I think that would be interesting. And then I think we can measure the basic stuff like inflammatory markers and, you know, basic blood, blood levels, things like that.

And then we're saying that lsd, because the evidence is pretty limited in LSD right now and the, we have the one study with worms that it's not ready for a, a protocol yet.

I think I would suspect that if there is a signal there, we'll see it with psilocybin and it would be a similar signal that we would see with lsd. So I don't think there's much point.

In doing both because LSD is not from a plant.

I don't think that matters too much, to be honest. I mean, like, LSD is, is going to be harder for you to do because it's not. I don't think you can do it medically in Oregon or college.

Yeah, that's what, I'm sorry, that's what I meant to say is. So it's, it's because it's not a plant, it's not legal in Colorado, therefore we would need to do it in Mexico or go out of the country. Yeah, yeah, the country. But you think it's, it's really secondary to doing psilocybin as a protocol in terms of longevity?

I mean, I would suspect that the, if there is a mechanism there, it's likely very similar between the two drugs, but it's, I mean, that's total conjecture at this point. Like there's just not studies to suggest it.

And then of course, this goes without saying, repeating what we had we said before, that there's, there's good evidence from John Hopkins that Mike mentioned showing depression and anxiety reduction where there's data. So for those of you not looking at it from a, a longevity perspective, but from just, you know, improving mood, then the evidence is pretty robust there. But our, our primary focus today is, is on the longevity potential of these drugs.

Yeah. Next I'd really like to talk about, about marijuana. We all talked about our first experiences and being exposed to this. This is also something that a lot of people use. It's much more freely available across the US than any of the other drugs we covered. And a lot of people use it for sleep, for example. So we get this question a lot. So Mike, what do we know about the upsides to marijuana? And then we'll cover the downsides.

Yeah, so this one, this one gets a little nuanced. There are some studies suggesting benefits of, of marijuana specifically around like anxiety and PTSD symptoms, some reduction of, of anxiety symptoms and PTSD symptoms. There's some Reduction of inflammation, so some anti inflammatory effects. And there's also some studies suggesting chronic pain relief. And then I'm sure most people have probably heard about like the antiemetic effects meaning like the anti nausea or anti vomiting effects of, of marijuana that's often used in cancer patients. There are these potential benefits. What's interesting though is if you actually dive into the research, most of the, most of the research has suggested that the benefits that we, that we just described are all from CBD rather than thc. So CBD is a chemical found in marijuana along with thc. THC is another chemical found in marijuana. Uh, the THC causes the hallucinogenic effects. So the like man I'm high effects, that's all thc. CBD is actually not hallucinogenic, but it is a compound found in marijuana that appears to convey a lot of the benefits around the anxiety, PTSD symptoms, the anti inflammatory effects, all of those things. And when you go to a cannabis store these days, you can actually like decide how much THC you want, how much CBD you want. Like you, you can determine what percentile of each one of these things you choose. So you ha. The, the consumer has the ability to sort of titrate the their dose based on what they're going for. I just think it's interesting that like people talk about THC having all these benefits or marijuana having all these benefits, but it's actually, it seems like it's mostly the CBD that has the majority of these benefits. From what we can tell, some people.

Are particularly prone to having a really intense negative experience with cannabis. I remember something about like you like needing to exercise or have a hot shower or something like that while being high because it's just like do you know what I'm talking about, Mike?

There's a few different things here. So like you, there are a subset of people who have a paradoxical reaction from THC where like meaning instead of feeling chill and high, they feel super like anxious, paranoid and self identity focused. And we don't truly understand why there's these two different reactions between people. But there are people who appear to be more sensitive to THC for that reason. And then there's this like this is, and this has really gotten worse in the last 15 years since THC has become legal. And they've been all this work to make these drugs super strong. But this thing called cannaboid hyperemesis syndrome that I saw a lot of in the emergency department where people have basically what happens is the receptors in the part of their brain that control nausea get flipped by the chronic use of, of marijuana. And all of a sudden instead of marijuana having this anti nausea effect, it starts having this extremely pro nausea effect. And these people get these like episodes of like, like terrible vomiting that lasts like a few days a week. And the only way they can feel better is if they take a hot shower. So you'd see these people and they'd be like, I've just been so nauseous, I'm puking all the time. And like, only thing that works, I take a hot shower. And you talk to their loved ones and like they've been taking like 20 showers a day. And I'm like, oh, how much, how much pot do you smoke? And then you find out like that they're a regular THC user. So that's, I don't know, just another interesting aspect of THC that whenever you take any medication on a regular basis, it changes the way the receptors in your body work for that medication. And with THC, you upregulate and downregulate receptors in your brain based on regular use of thc. I do think there is something to be said for regular use of THC and how that could potentially even increase anxiety and depressive symptoms and sort of habituate you to regular use so that you need to use it regularly in order to prevent that regular anxiety. Just like smoking a cigarette causes, you know, this release of anxiety once you get that nicotine protein. It's the same general principle in terms of what's happening in the body.

So we covered some of the upsides and some of the downsides, but there are some other things in things you should know when consuming marijuana. For example, lung cancer that's pretty significantly increased. And this is for folks that are smoking weed or just eating it. What's the stats here, Mike?

Yeah, so people who are smoking on a regular basis are exposing themselves to, to chemicals and to smoke in your lungs, which you know, we know for multiple reasons is, is bad for you. And we've got years of history of smoking being bad. So the actual inhalation of smoking marijuana can increase your risk of lung cancer and by like 2.8 times increased risk. So about a 280% risk of, of lung cancer, which is not good. So that would definitely be a check in the, in the diet category for smoking marijuana at least. There are other ways obviously to ingest it. You can, can, you can eat it, for example, which is a common, a common way these days using, using edibles.

And Then also things like suicide risk being almost nine times higher with regular marijuana smokers. Is that accurate?

Yeah, they're, they're specifically talking about people who have cannabis use disorder. Um, and in tho at that population the all cause mortality risk is increased by about a hundred and twenty, eighty percent. And that's, that's more than just I, you know, I use marijuana. That's a, a medical condition where somebody is actually dependent or addicted to cannabis, meaning that they basically have to have it in order to prevent negative symptoms from not happening on a regular basis. So this is someone who is a, not just a daily user but multiple times a day and has negative side effects if they don't get the dose, basically. So it's a specific person, but there is a significant increase risk mortality for this people.

And then how about the effect on epigenetics aging generally? Does marijuana have any kind of correlation positively or negatively?

Yeah, interestingly so there was a study on this and they looked at like 5,000 people I think, and they showed that just recent marijuana use was associated with an increase in biological age according to the grim age epigenetic predictor. So each, for every day of, of recent use there was a one month increase in biological age. So it does appear that there's a signal there for an increase in epigenetic age just with marijuana use now unclear whether that is related to smoking only or if that could be also associated with eating as well as smoking marijuana. But certainly a concerning finding that would put it more also in the diet category.

That's fascinating. Okay, so sounds like marijuana is not on the list for potential longevity protocol exploration, is that right?

Yeah, maybe. I mean, I think there's still more to learn here. Like, you know, there are, like we mentioned at the beginning, there are those benefits at least of cbd, anti inflammatory, anti anxiety, there's the benefits of sleep that we mentioned. So there, there are potentially some areas that could be beneficial, but I think like just with anything like the dose makes the poison. So this is definitely one of the situations where if you are using marijuana on a regular basis, especially if you're smoking it, it may be leaning more towards dye rather than longevity.

Hey Mike, do you want to check out the studies that Ali and Lauren posted on sleep?

Yeah. So just looking at some of the, some of the studies that they posted over here. So two weeks of balanced THC, CBD oil took insomniacs and basically cured 60% of them. So put them from unable to sleep to basically able to sleep. And they also saw an increase in melatonin in those, in those patients as well. So basically taking the cb, thc, CBD oil before bed led to an improvement in overall sleep duration as well as improved melatonin, melatonin release, which is kind of interesting. And then there's another study that looked at effects on sleep architecture, showed decreased sleep latency, increased deep sleep, decreased or decreased REM percentage and REM density. So that's interesting. So that could be net, potentially a negative piece. RIM latency was prolonged. That's actually negative as well. So kind of like mixed findings in sleep. It looks, it looks like it's interesting. I've talked to a lot of people who use, use thc, use pot regularly for sleep. And the, it seems like just in my like own experience and talking to, talking to patients and friends, some people seem to love it and some hate it. Like there's a, there's definitely like a dichotomy there. Like there's people who are like, swear by it, say like, this puts me to sleep, I have amazing sleep. They track their sleep with aura. It looks good, all those things. And then there's people who are like, absolutely no way. Like, makes me paranoid and anxious and I can't sleep. So it's, there's a clear dichotomy there for sure.

All right, Mike, so if someone's been passively listening to this podcast and they've heard us weave in and out of this topic of the pros and cons and the risk of marijuana, Lauren just posted here in our chat here that she said there's no clear cut clinical consensus that cannabis reliably improves sleep across the board. As we were going through the evidence, that's what this entire thing felt like. Whereas with psilocybin, it didn't seem like we had a similar complexity where it seemed like it was a potentially a cleaner path for improved cellular mechanisms. But then again, maybe there's just a limitation, we haven't studied it enough. But with marijuana it seems like the data is, it's much more complex. Is that a fair assessment or do you think that's just that the research on psilocybin has not, is not as well studied as marijuana.

I think it's multifactorial here. So yes, psilocybin is less studied than marijuana. Marijuana is more studied. It's a, it's a hot topic in that for many years there was a, a negative cultural sentiment towards marijuana. So during that time frame you saw a lot more negative studies come out. And now there's been a flip and now there's more positive studies. So like, it's interesting how like cultural norms play into scientific research and that's probably muddying the water for us more than it may be muddied by itself. Or it could be that there is a very complex mechanism here, here that's very individualistic, which is maybe the way I would lean to it that like, it sort of depends on who you are and how your brain chemistry works, whether you have sleep benefit or sleep downside from, from marijuana. Um, there's certainly like I, I believe that there is a, there's a wealth of evidence that there are some benefits regarding inflammation, potentially sleep in some people, um, anxiety in some people that speak to the opportunity for marijuana being a positive experience for people. Yet there are obviously downsides as well. Smoking is clearly bad. Using it on a regular basis is clearly bad. So while I think there's nuance, I think if you are someone who appears to have subjective improvement and you can track it maybe with, you know, your, a sleeping device of some sort, then it might be a, a beneficial drug for you. But you want to make sure you don't get into that realm of cannabis use disorder disorder where you're using it multiple times a day, every day. It's a thing that you have to have because then you start seeing those negative side effects again. So hopefully that distills it at least somewhat for some people. But unfortunately I think this is, this is one of those answers where you have to be real and say like, you know, it's going to be different for different people.

I was recently with Snoop Dogg and I had the opportunity to talk to him about. I mean, he was high, as one may expect when I was talking to him. So I'm not quite sure how much he heard what I was saying. But he's, he's been smoking for quite some time now. I mean for as long, I guess. Like, I think he was the earliest of adopters.

I gotta imagine Snoop just like, is like, he's, it's baseline for him at this point. Right? Like I'm so. I'm sure he heard everything you're saying. Like he probably, at this point, he probably thinks better when he's smoking.

This is my subjective opinion. I struggle to identify anyone in my life that consistently uses weed, any version of it, edibles, and of any variety that I would say is like in some ideal state. Maybe there's exceptions I'm unaware of, but I just generally do not know regular users that are just doing. They're thriving.

I wonder how many people in your life you don't know? Regular users.

Exactly. I agree with that. It's definitely a risk of my. That I the data sets complete. So yeah. So if you're listening to this and you are a regular user and you think you're thriving, first check with your friends and think, well, first, like you need friends that are not regular users and then once they are not regular users, then survey them and inquire of them of how you're doing. Then put your comment in the section below. Let us know if we've not assessed. If I've not assessed this property.

Also send us your biomarkers. We want to check that too. Perhaps a more reliable source than your friends opinions.

That's a good point. Kate.

We want to know, Brian, did you smoke with Snoop Dogg?

With Snoop. No, I didn't. I've tried CBD and THC and then various combinations of those two. And whenever I do it makes me feel dumb. It makes me feel like my, my. Like I lose 50 IQ points and I just can't think. I don't find it enjoyable. I find it to be just not stimulating and kind of claustrophobic. So I don't enjoy it. I tried it for sleep. I tried THC for sleep and it gave me a sleep hangover and a headache. So it didn't work. I think it maybe had some small effect of a deeper sleep the first night, but then it quickly wore off in the second, third night. So I've had zero success with any form of marijuana. But then again, I haven't done rigor. This is like years ago, before we were doing rigorous studies and measuring. This is just like trying things out when it became legalized.

Funnily enough, I have. My experiences in trying marijuana have been the camp that Mike described where it is not for me. I have a hundred out of a hundred horrible experience, like absolutely excruciating. So I've definitely learned it's not for me.

Same. Yep.

Really?

Wow.

That's fascinating that all three of us are like that.

When I was a kid, it was a very positive experience.

Really?

Yeah.

Oh yeah. Right.

Yeah.

Until, you know, early 20s maybe. And then it flipped and it turned into an extremely negative experience. 100. 100 negative. Just like you, Kate.

Wow. Yep.

So if we did this podcast. Hi.

That'd be very interesting.

What do we think would happen?

None of us would talk and we would stare at one another with paranoia. We would just sit here staring like what?

How much of like I know in pop culture, the conversation a lot is around. Like these are really hyper optimized compounds. Now how much do we, do we have any information on that Mike? Like how much that might be affecting the day to day experience, people?

Probably a lot. Yeah, I've, I've seen, I don't remember off the top of my head, but I've seen something like, you know, a hundred, two hundred percent increased amount of actual chemical in a standard dose. Like yeah, just this is not our parents marijuana that's being sold at stores these days.

Okay, so if we're going to summarize this then if we cover last episode and also this episode, we would say of the rankings of these various recreational drugs. I shouldn't even say recreational, just say drugs. Psilocybin is among the top of longevity friendly, as is ketamine. LSD is interesting. Mike, you said because of the similarity of its mechanism of action. DMT is emergent. There's not a lot of evidence there, but there's some early emergent evidence that it could be beneficial for the brain. And then marijuana, which is mostly negative evidence and occasionally you've got some acute applications that may work, but heavy usage may be damp. Is that a fair summary of how we would score psychedelics for longevity?

I'm hemming and hawing because it's just like, there's just not a ton of data yet. But based on the data that we have, yeah, I think that's, that's a fair start. And then also thinking about like the safety profile of most of these medications being you know, fairly positive for the psychedelics, obviously very negative for the drugs that we mentioned earlier that are not safe. I think that's reasonable. Um, I, I also want to just like, sorry. I feel the need to caution people about like just going out there and be like, I wanna, I wanna live a long time so I'm gonna go take 10 grams of psilocybin. Like these, all of these drugs come with the like whopping caveat that like set in setting is important. Making sure you're understanding what you're doing, having a guide, having someone who has experienced all those things are extremely, extremely important. So like please don't take this as like a approval to go and just like start experimenting without any thought or protocol beforehand. That's obviously not what, not what we're about here.

And in fact make sure you definitely consult with your, whoever your medical provider is or whoever your team is looking after your care because you want to do this with the appropriate precautions if you do this at all. And definitely not to say we are encouraging it.

And then the things to stay away from, cocaine, meth, heroin, fentanyl, Fentanyl. You have to have your don't die drug kit for a nasal spray we put up on screen last time and also the test strips. Just don't put yourself in a compromised situation. And what a terrible way to, for life to end in that kind of accident.

One note is like the three of us, we just talked about how we don't personally use weed. And I know a lot of people out there have a lot of positive experience with weed. Like chronic pain is a really big one, obviously, but getting to sleep and we know the importance of sleep. So just to call out that there are definitely use cases for weed that people have self reported positive benefit from. And I guess this brings us back to what we've always said, which is measure yourself. So make sure, you know, is your sleep architecture being impacted by weed, for example.

Good point, Kate. I was trying to elicit that nuance, but yeah, I think maybe all of us being non users maybe made the negative come across a little bit more, more strongly than the positive. There's certainly some benef. Some benefits that some people have with regular use of marijuana.

Yeah, actually I would love to hear from you guys in the comments. Those of you who do use weed successfully in your life, I would love to hear what you're using it for and your approach to doing so. I do admit that I have a negative bias towards it through my own personal life experience and my own interactions. But I'm entirely open to being incorrect on this and that I just am unaware of the positive use cases that are genuinely helpful to people in ways that other things are not. Because I know when you're trying to deal with a complicated thing and nothing else solves that problem, that when you do find it, it's a gem. So that may be the case where marijuana really is plugging that hole that just nothing else can solve. And that would be a really important for others to understand and that we don't overly bias this conversation for others who could benefit from the same thing.

One thing we didn't cover, which would be cool to cover in future episodes, would be mdma. We didn't cover that at all, I don't think.

How did we not cover mdma?

That seems.

Yeah, it's like that's the one that almost got FDA approval for, for the things we're talking about.

Why don't we put that as the next one?

Yeah, sounds good.

Okay, friends, there you go. So again, a reminder this is not an encouragement to do psychedelics. This is a conversation to discuss the potential health effects and complications of various drugs. So be mindful, be careful, make sure you're only doing things in a legal and safe setting. These things are not to be played around with. You definitely don't want to be in a compromised situation. Please let us know your thoughts, the things we missed in conversation, and what we should have been identifying for evidence that we missed, and your personal life experience with things, for example, like marijuana. All right, 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.