What's the deal with psychedelics?

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19:43Emily Oster:And we're back. What's the deal with psychedelics? Emily, psychedelic medicine is an incredibly new field boosted on the backs of some really interesting data that we're going to talk about and then a whole lot of influencers and marketing and amazing anecdotal stories. So let me just say before we get into this, I think that this has really now stepped into more of the mainstream, the daily, the New York Times podcast, which is a very serious podcast frequently about, you know, China and stuff, had a whole episode with a reporter who had sort of gone down to Mexico to do a, have a psychedelic experience and to talk about like this being transformative for his relationship with some, some childhood trauma.

20:35So I think this has gotten between that and Michael Pollan's book. And so I think this has gotten into the zeitgeist even beyond influencers on the internet who for sure are also talking about it. So good topic.

20:48Emily Oster:Yeah, absolutely. And the way I want to kind of approach this is first, let's do some science. Let's talk about how psychedelics work, right? And then we'll kind of go in if they work for various conditions. We'll hit on a few mental health conditions like PTSD and depression and addiction, which I think a lot of the data is really interesting. But then I think it's worth talking about, what about people who are otherwise healthy? Are there potential benefits to supplementing with psychedelics from time to time? It's not like vitamin D though. It's not an unsupervised experience. I want to think about psychedelics starting with neurobiology.

21:27Emily Oster:And there are three functions that the brain does that psychedelics mess with. And I think if you understand those functions, you get why the psychedelic experience is the psychedelic experience. The first one is called reality testing. So have you ever noticed, Emily, that in real life, when like your door bursts open and a goblin carrying machetes jumps through, you're like, that's probably not real. But if that happens in a dream, you're like, yeah, that's of course, like these things happen. Right. Right. Your brain is reality testing all the time when you're conscious and awake. Like it is getting stimuli from all over the place, not just the things you see and feel and smell, like tons of stimuli, but also just like random electrical firings in your brain that are happening all the time.

22:15Emily Oster:And there's a whole system designed to like make sure that the inputs correspond with your knowledge of the world, right? Like things don't fly up into the air unexpectedly. Like all of those things, that's what reality testing does. It gets shut down during dreaming, which is why your dreams can be so believable, even though bizarre things are happening. It is also shut down by psychedelics. And so all of a sudden, all those inputs that normally your brain would filter out is like, that's not consistent with reality. It's like, yeah, sure. That makes sense. Sure. That tree can be melting. Like, why not?

22:47Emily Oster:So that's number one. Yeah. So this is sort of like if I'm in my conscious mind and I out of the corner of my eye, I see something that looks like, you know, buffalo running down the street. My brain is sort of like, well, that's obvious. Like, it's coding. That's obviously not a buffalo. Exactly. And I either look again or I just am like, obviously, it must have been a dog. It might not even raise to conscious awareness. Like you might not even know that you saw a buffalo out of the corner of your eye. Yeah. Okay. Great. The second thing and something I think is really interesting is technically known as salience, which is that your brain assigns a level of meaning to every experience you have.

23:26Emily Oster:Like, is this important? So evolutionarily, salience is like you ate some berry and then you get like horribly sick. And your brain will attach a little tag to that memory. Like this is an important memory, right? Like this is meaningful. And those memories get processed differently. They get stored differently. So it's like, okay, in the future, you're not going to eat that berry again. Whereas like walking from your car to your office every day, your brain processes that. And it's like, this is not important. Like we don't need to remember this. This is nothing important is happening right now.

23:58Emily Oster:And this is really important because otherwise your brain gets full and you're like that guy in the far side cartoon. Psychedelics ramp up the salience metric of everything that is happening, which is why if you're sitting quietly on your couch and nothing in particular is happening, but your brain is saying like, this is really important, right? You have to have some explanation for that cognitive dissonance. And one of the ways people explain that is they're like, I'm in the presence of something bigger than me. God is here or an entity is here because this very banal thing sitting on your couch all of a sudden feels really, really important and meaningful.

24:44Emily Oster:this lack of reality testing and increase in salience is also seen in paranoid schizophrenia which is why paranoid people have hallucinations and also you know if you're just sitting there like watching tv and it's just a newscast but your brain is saying this is incredibly important you can see how you might jump to the conclusion like oh they're talking to me right this is about me, right? So in fact, the psychedelics, when they were originally discovered, were called psychotomimetics, like things that give you psychosis. But fortunately, with the psychedelics, it is temporary. And with schizophrenia, obviously, it's permanent.

25:26Emily Oster:So I think this is a good way to start thinking about what's actually happening here. That is very cool. So these, the compound, I think one of the things that's interesting about psychedelics is that these compounds have been around and used for, I think, probably all of human, you know, almost all of human history. So, you know, we associate in the kind of modern era, we associate the LSD with, I believe it was discovered by Albert Hoffman, but we associate it with Tim. Timothy Leary. Timothy Leary. Thank you. But many of the compounds that are sort of used in some of these for psychedelics are from plants or mushrooms or whatever and have been in use presumably again for millennia.

26:18Do we have a sense of what people use these for before like using it for PTSD? I assume just for hallucinating because it's fun.

26:28Emily Oster:I mean, in a lot of indigenous cultures, they're used for spiritual purposes. I think ayahuasca is maybe the one that people will be most familiar with, where the idea is to commune with something greater than yourself, not just to have a crazy trip. And there's a whole social fabric around it, which is really interesting. And I think even potentially part of the therapeutic benefit that can occur with some of these is what surrounds the experience. In fact, a lot of the studies that we'll talk about like really need to couple the drug with something, whether it's like psychotherapy or something like that to kind of allow the effects to take root.

27:11Emily Oster:There's a lot of psychedelics out there. You've alluded to a few. So I think we should just sort of like maybe say a couple of them. Should we list them? I mean, we could list them. I don't know. Do you want to give us a rundown of like what you see people talking about, Emily, in terms of what psychedelics we mean? Yeah. So I think the there I would sort of say there's a couple of categories that I hear talked about a lot. So one is the kind of psychosybin. Psilocybin. Yeah. Maybe I begin where people talk about usage in a kind of like a true like tripping state. we see I think a lot of discussion of ketamine I would say ketamine is the one where I hear people both on the internet and actually in my life talk about using ketamine so if you hang out in LA at all everyone will talk about how they're doing ketamine it's not literally everyone but all the people that I've encountered recently in LA you know we're explaining like this as a sort of standard part of kind of a psychological treatment.

28:11Yeah. And then MDMA, which is, it's ecstasy, right? I mean, yeah. Again, sort of not so much for the therapeutic uses, but almost like for relationship improvement. Interesting. Now that we're adults, I feel like everybody who talks to me about psychedelics is talking about it, not for like, this is going to make my rave more fun, but like, here's how I'm going to improve my marriage.

28:34Emily Oster:Okay. That's what it is to TV46, Perry. I love this. I love this so much. So great. I think it's worth saying that the hallucinogens like psilocybin, LSD, MDMA, all work in part on a specific receptor in the brain, the serotonin 2A receptor. Ketamine is not quite a hallucinogen. It doesn't work on that receptor. It's what's called a dissociative anesthetic. So that experience, as I understand it for ketamine is more just like you feel like you're not really in your body, like you're not kind of a participant in reality. So it's definitely an altered state, but it's not quite the same reality testing, salience stuff that we talk about with the hallucinogens.

29:23Emily Oster:So, Emily, we've gone through kind of a big list of psychedelics. There are others that we won't even get around to mentioning because there's not as many studies on them. But I think one thing that I often hear is like people kind of draw a line between something like mushrooms, which it's like, oh, that's from nature, like an ayahuasca, which is a, you know, something that grows versus something like LSD or MDMA, which are synthesized chemicals. Do you think that safety goes along with the fact that something comes from nature versus a synthesized in a lab? Or like, how do you how do you think about these?

29:58Emily Oster:Or do you not divide them at all? I think that most of that division is kind of fake in people's heads. I mean, these are all working on some, they're all like sort of chemical processes that are working on a brain receptor and often on the same brain receptor as each other. it is true that the synthesized versions tend to be much more potent and a much smaller amount. And so I think there's a sense in which like it's more difficult to take too many mushrooms than it is to take too much LSD because you could pretty easily take like quite a lot of LSD without realizing it. And the mushrooms like, you know, there's a little more processing of the experience.

30:37Yeah. But up to that issue, I think these are very like it's just a chemical. And so it's not like one of these is natural and one of them is not natural. They're just chemicals that are like produced in different ways.

30:48Emily Oster:Can I tell you an amazing - We should say that ketamine is a schedule, like most of these drugs are schedule one, which means they are not legal outside of a research context, I believe. And it's even really hard in research to get the approvals to do it. Yeah. Ketamine is schedule three drug, which means it can be used in certain circumstances. Oh yeah. We use it all the time for, oh my God, we use it for kids when they have broken bones. Really? Yeah, yeah. The first time I had a kid in the ER when I was a med student, I guess. No. Yeah. I guess I must have been a med student. Kid had a broken forearm.

31:22Emily Oster:Little kid, the poor guy. And, you know, the orthopedic surgeon was going to come in and, like, reset it and put it in a cast. And they gave the kid a little bit of ketamine. He, like, zones out. Like, not asleep. Just, like, not there. And they, like, you know, do his arm and everything. And he was totally chill. It's really great. It's a great drug for that. Actually, now that I think about it, they use ketamine all the time on the pit. Ketamine and rock, I believe, is Dr. Robbie primarily. So for those of you who have not yourself set a small child's arm, you can think about Dr. Robbie doing it.

31:53Awesome.

31:54Emily Oster:Just a brief tangent on the MDMA for relationship status. There is a totally amazing study of octopuses where - It's octopi, but fine. Oh, okay. I believe it's Octopoda. Actually, go ahead. All right. Current biology, 2018, they used these octopuses that are, okay, the two-spot octopus, which are notoriously antisocial and attack each other and stuff like that. And they put them in a tank together, but there was MDMA, like this ecstasy stuff in the tank. And the octopuses like got gentle and were like stroking each other's tentacles and stuff like that. So when you say it's good for like a marriage, I am on board.

32:49Okay. So there are many things one could say about the detailed chemical structures of these different drugs. But I think in some ways much more interesting and practical for people is the question of whether they are effectively used in treatment of various things and also the question of whether you would like to take them even if you are not looking for treatment. So I would say we should turn to that. And I actually wanted to start with sort of two big picture pieces of this, maybe three. So one is that by and large, these medications are used not like you would use Tylenol or even, you know, a statin.

33:34Like it's not like somebody gives you a bottle of, of, you know, MDMA and every day you, you take it and we can talk about micro micro dosing, but most of this is like a, a one time, a couple of times, small number of treatments under the supervision of a doctor. Many of these things people are doing in other countries because of drugs or schedule one. And so this is like a sort of pretty fundamentally different idea behind, you know, does this treat the following disease because it's not an ongoing kind of pill form treatment like we often talk about. I think the second thing is we've talked before about placebo effects.

34:15This is a place where placebo effects, I think, are incredibly complicated, even to conceptualize, because we are talking about things that are happening in your brain, which is where a placebo effect also happens. And in these cases, it's almost impossible to double blind. So, you know, these trips, when you talk about this, but people describe these as like the most meaningful experience in my whole life. It's hard to be like, well, do you know if you had, like, how would they know if they had it or not? It's like one group of people -

34:44Emily Oster:Are you sure it wasn't a really good sugar pill? Right. It's like, you know, and I guess the third piece about placebos here is I'm not even, it may not even matter, I guess. Maybe the whole thing is a place. I'm not really sure how to conceptualize it, but it's worth thinking about almost none of this can be truly placebo-controlled the way we would placebo-control a vaccine or a medication where you give people a sugar pill, you see if their cholesterol goes down and that's just easy to understand. And when you're talking about mental health, as we will be, placebo, if you tell me you're not depressed anymore.

35:20Emily Oster:I guess it worked. Okay. Great. As long as it works and it lasts. Yeah. So I thought maybe we start with PTSD. And the reason I want to start here is because this has gotten a lot of press recently because of President Trump meeting with Joe Rogan to specifically discuss psychedelics. And I'm going to play you a clip now of President Trump talking about Ibogaine. It's called Ibogaine treatment. Ibogaine. Remember the name? Is that pronounced relatively properly, what you said? I don't want to get it wrong. Ibogaine, because it's so important and experienced an 80 to 90 % reduction in symptoms of depression and anxiety within one month.

36:13Emily Oster:Can I have some, please?

36:17I'll take whatever it takes.

36:20Emily Oster:So first of all, does anyone else, like whenever you hear ibogaine, are you like, I spent the past few years building up an immunity to ibogaine powder. Is that, does anyone know? Okay. That's the princess bride. Hello, Jennings. How are you? Welcome back. It's iocaine powder from the princess bride. I know, but ibogaine always sounds like that. Um, so Emily, President Trump is referring to a paper in Nature Medicine, uh, that had, I mean, I have to say pretty, pretty incredible effect sizes here for, for Ibogaine for PTSD. Do you want to run us through that one? Yeah. So they, these guys are talking about a paper in Nature Medicine from 2024, uh, in which they're looking at treatment for traumatic brain injury, which is unfortunately can be common in veterans and is associated with depression, anxiety, PTSD, other kinds of functional disorders.

37:18This is proven to be very difficult to, very difficult to treat. So they took 30 men with, I would say mild traumatic brain injury, and they treated them with magnesium ibogaine. The paper is not a clinical trial, so it's not a randomized trial. They took these 30 people, they treated them all, and so again, it's hard to separate from what might have happened anyway. However, the improvements in functioning were really quite big. They have improvements in depression scales, improvements in PTSD, improvements in anxiety. And these are pretty large increases. I'm not sure exactly how we want to size them, but they are all incredibly significant and a very difficult to treat area.

38:14Emily Oster:Yeah. I mean, if you look, I'm just looking at the graph with the paper. And of these 30 people, you have, yeah, you have like 28 of them with like who went from moderate PTSD to minimal PTSD, which is amazing. After a single dose of this ibogaine therapy, I think it's worth saying that, hey, it's just one paper. There was another ibogaine. It's not a randomized trial. There was another ibogaine study of PTSD that actually did not show quite a strong effect, still showed effects, but not like this dramatic. And so, and there's no randomized trials whatsoever, basically. If you look, okay, if you look, you'll find one randomized trial of ibogaine, but it was a safety study.

38:57Emily Oster:So they were randomizing just to dose. So it's not like there's a control or anything like that. This is clearly a great area for research. And I'm actually enthusiastic that the administration is considering rescheduling some of these drugs so that they can be easier to research. But, you know, what we want in these types of trials is yes, we want placebo controls, even though it's incredibly hard to control, but we also want longer term outcomes, right? Like a month is great, but six months, a year, two years, what's the mental health of the people who got treated? Yeah. And I think that there's a, I mean, people have experimented with treatment with MDMA, with psilocybin, with ibogaine, like all three of these have come up in this treatment.

39:40Relaxing the rules about this would let researchers figure out things about randomizing, but also dosing and what is the best approach to dosing and how many times you need to do this and does it need a re-up every six months or what is the sort of treatment protocol? The other issue is, of course, when you only have three studies of something and they are all significant, one worries a little bit about did actually 25 different studies of this get run and only three of them get published, that's where you need pre-registered, large, randomized controlled trials, which are only going to happen if these drugs are easier to use in a trial setting.

40:23Yeah.

40:23Emily Oster:Yeah, absolutely. So we'll close the book on PTSD. I've been kind of interesting, some good data for MDMA and very preliminary data on psilocybin just to run through the psychedelics that are being used here. Let's move on to depression, though. Let's talk about depression. Yeah. I mean, this is obviously incredibly common and a place where there are current therapies, obviously. There are multiple therapies for depression, both pharmacologic and non-pharmacologic. But I think the public understands that the standard of care right now for major depression disorder, which are the SSRIs, are moderately effective and come with some side effects that people find not great.

41:08Emily Oster:And so if you did have something else, you might be open to something else. Is that fair to say? Yeah, I think that's fair to say. I mean, I think the administration has recently been quite negative. RFK Jr. has been quite negative on SSRIs. And I think that you know, that's probably some of his statements are overstated. But I think it is it is true that these have not proven to be a magic bullet for many people with depressions. They have been very helpful for for a large number of people, but not so amazing that we should not be looking for other approaches is how I would is how I would put it.

41:42And this is a place I don't know if you want to talk about my favorite thing here is the 2023 JAMA paper, because JAMA is such a great journal. Do you know that one time Perry published in that? I understand that you've also

41:53Emily Oster:published in JAMA, Emily. Do you want to tell us about the large clinical trial in JAMA of psilocybin on which neither of us is an author, but we still like it? Yeah. So this is a study in 2023, which took 104 adults with major depressive disorder and randomized them to a single dose, 25 milligrams of psilocybin. And also, and as I said, this was important, 11 hours of psychological support, which included like preparation for the psilocybin dose, support on the dosing day. And then after that, what they call integration, which is like processing the experience that you had. They did do a placebo control, 100 milligrams of niacin, which is a vitamin, but at that dose, it's going to cause some flushing.

42:42Emily Oster:Now, I don't think flushing is quite the same as a psilocybin trip, but it's not nothing at least. So if they didn't know what psilocybin was like to begin with, maybe they thought they were getting something. They might have thought it just made them hot. Okay. Yeah. I don't know. But they also got that psychological supportive protocol. The primary outcome was a score, a depression score. And I won't go through the score, but I'll tell you, it went down by 12 points, which was a highly significant difference. Like that is a clinically meaningful difference, a 12 point reduction in depression scores.

43:17Emily Oster:And that was out at day 43. The sustained response rate, which meant like you had sustained improvement in symptoms out that far at day 43 was 42 % in the psilocybin group versus 11 % in the niacin group. So this was, you know, a trial that said, okay, we've got something here. Yes, you're integrating it. But remember, it's only one, it's a single dose at one time. There's a bit of biology here. These drugs that stimulate the serotonin-2A receptor might increase neuroplasticity, which means you can form new neural connections. So psychiatrists and psychologists are wondering if that initial dose kind of shakes up your brain a little bit.

44:03Emily Oster:And then it's actually that integration phase where, you know, now the patient is sort of ready to make those cognitive changes that's going to improve their underlying status. So it's both the drug and then like which kind of shakes things up and then you kind of put things back together in a better way moving forward. That's all hypothetical, obviously, but pretty exciting results. Yeah, I thought that was exciting. I mean, not everything in this space is as exciting. And in particular, there's a Najum paper from around the same time, which did a trial of psilocybin versus a standard antidepressant.

44:41Emily Oster:Yeah. Oh, yes. An SSRI. This is a better control, like active. A better control, not just flushing, but something is actually, you think about like this would be alternative. So the primary outcome in the paper does not show differences in efficacy. see there are some secondary outcomes which do, although they test many of those. So I would say the results in this one were decidedly more mixed. But both of these together tell me, okay, you know, we're doing these trials with 60, you know, 60 or 100 people. We need to do these trials with 1 ,000 people. And for depression, unlike, you know, PTSD, there certainly are 1 ,000 people you could find with depression who one could experiment on.

45:25Emily Oster:Absolutely. Absolutely. The issue versus SSRI is like, you want to be a little skeptical when you hear people saying, you know, oh, these things blow SSRIs out of the water, like SSRIs don't work and psilocybin does. You know, the actual trial here says like, eh, they're close. But again, there are other reasons that you might, you know, a single dose of psilocybin might feel a lot better to people than a daily dose of an SSRI going on forever with the attendant side effects that one might have with those. The sort of flip side, not the flip side, I always think of depression and anxiety together, the two most common psychological disorders affecting people in the United States.

46:04Emily Oster:Anxiety, when it comes to psychedelics, always made me a little nervous, just in principle, I think because the psychedelic experience, as I understand it, can be anxiety inducing. In fact, some of the adverse events that were reported in some of those depression trials were like anxiety. And you can sort of imagine that if you're an anxious person already, and then all of a sudden the walls are melting and you feel like you're like melting into the floor or whatever, like maybe that's not great for you. But even here, and I should say like, we don't have nearly as much data in anxiety yet as there is for major depression disorder.

46:41Emily Oster:But I was looking at this 2016 study from the Journal of Psychopharmacology. Did you see this one, Emily, that seemed like there might be some use here? This was a pretty high dose of psilocybin. Yeah. They're treating people with cancer-related anxiety and depression. So it's a kind of combo group and they're giving them a fairly highly dose of psilocybin. But it does seem to have improved anxiety, depression, and they're kind of decreasing cancer-related demoralization. That's from the paper. So positive there. Not enough data to be sure. Not enough data to be sure, which is the tagline for this episode.

47:25Emily Oster:If you're an anxious person, this is maybe not the thing to jump right into quite yet. The other big category before we get to just the healthy people who are curious - Drugs, alcohol, cigarettes. Addiction. So what Joe Rogan was talking about when he was meeting with Trump actually was not Ibogaine's effect on PTSD, but Ibogaine's effect on addiction. And like all things Joe Rogan, he has some story. It's always an anecdote with him, which is he had this guy who was addicted to heroin and everything was horrible. And then single dose of Ibogaine and cleaned himself up and we're off to the races.

48:07Emily Oster:Again, there is no randomized trial for ibogaine whatsoever. There's some open-label data, though, I found. There's a study of 191 people who were using opioids or cocaine, and they did show that a single dose of ibogaine diminished withdrawal symptoms and drug cravings at one-month follow-up. This comes from Frontiers in Pharmacology in 2018. You know, this is open label. There's no control here. It's a little hard to say. Any thoughts on Ibogaine for addiction? I mean, again, I think this is a space where people are, it is very treatment resistant. And so having something to try is interesting.

48:56We also worry that when people get to the point, at least in this case, I worry, you get to the point where like, I'll try anything. I'm going to go to Ibogaine. Maybe you are, that actually is a signal of sort of motivation to fix things. And so if you thought of this as like, we're just going to assign this random, like we're going to assign this to people, it might, it might show up differently. There's actually a bit better data for psilocybin in alcohol use disorder. I was trying to think this is from randomized trial data and we see, you know, a reduction, uh, sort of a larger reduction in heavy drinking days with psilocybin versus the, in this case, versus like control.

49:34Emily Oster:You used to have Benadryl as a control in this study, which is another, it's like, I kind of, it's sort of like, it's fun to imagine these scientists being like, what the hell are we going to use as a control? Like, let's give someone Benadryl. What do you have? What are you looking at in your cabinet? Should we drive Pepsid? No, no, Benadryl. What makes you feel weird, but not too weird? Yeah. Benadryl is a good one. And then, I mean, I wondered here about how large this effect is relative to GLP-1s, which we're constantly talking about. Like, you know, like for the alcohol stuff, it seems like we're increasingly having some other options.

50:10Right. Okay. Can we talk about healthy 40-somethings like us and whether we should have this experience?

50:17Emily Oster:I have to say, I wrote about a new article that just came out recently, was looking at the effect of a single dose of 25 milligrams of psilocybin in healthy 40-somethings who were psychedelic naive. So like - Just like us. Just like us. I was like, Spider-Man meme. Like, oh, that's me. Like, you know, who are these people? Because all these prior studies, even the studies in healthy people in the past, like many of them are people who have had experiences with psychedelics. And so it's like, maybe it affects your brain, but it already did affect your brain. Anyway. Right. This is a super cool study.

50:57Emily Oster:So psychedelic naive, otherwise healthy 40 somethings, they got 25 milligrams of psilocybin or one milligram of psilocybin, which is sort of a subtherapeutic dose, which they gave them first. And then they did EEGs of their brain and a functional MRI a month later. So the question was like, were there acute changes in your brain waves and then were there lasting changes one month down. Small study still, 28 volunteers for this. To your point, 27 of the 28 rated it as the single most unusual conscious state of their entire lives. Yeah. One guy didn't, who's like awesome, obviously. The guy's having a lot of great stuff happening.

51:38Emily Oster:He said he was in the top five, but I'm like in the top four. I would be curious about what number two was. Yeah. So to break this down, the EG findings really interesting. What they showed acutely was a reduction in alpha power, which is alpha is are the waves that are sort of like they're like the lid on your brain. They're the they're like our self-control almost like they sort of tamp down all the crazy stuff that's going on under the surface. So it's like calm, restful consciousness is alpha waves. That power goes down, which sort of means like the lid is off. And then the EEG complexity went way up.

52:17Emily Oster:So, you know, so all of a sudden, just like the stuff that was coming out of the brain was much crazier than what had come out of the brain with a one milligram dose. That sounds right. It feels right to me. I mean, it's so, it makes me so curious. That's exactly, I was like, that sounds, that sounds kind of amazing. Now, one month later, they did some stuff. They did an fMRI. And honestly, it didn't show very much. Like it didn't show like dramatic structural or functional changes in the brain. Okay. Which is different than what has been shown in some like depression related studies of psilocybin.

52:56Emily Oster:Maybe because maybe if your brain is kind of like functioning normally to begin with, like I don't know what's going to change as much or something like that. They didn't show that. But psychological well-being was significantly higher one month after the 25 milligram dose versus the one milligram dose. And they measured the day after you took the thing. They gave people a survey of insight. So they asked questions like, do you feel this experience led you to think about yourself differently? Have you learned important new ways of thinking about yourself and your problems? That's a measure of insight.

53:33Emily Oster:And the people who had higher insight had higher well-being at the one month mark. So there's this little bit of like a mechanistic, like you take the drug, you kind of think about it, you think you work through some stuff, you kind of shake up your brain. And then a month later, you're doing better. What I can't tell you is because there's no like, yes, it's different than the one milligram dose, but like, obviously that's not, it's a totally different experience, right? Like 25 milligrams is the most unusual conscious state of your entire life, one milligram, they had like no sensations whatsoever.

54:06Emily Oster:You're feeling better a month later. Is that because something fundamentally about you has changed? Or like, do you feel good a month after a nice vacation, right? Like, is it just the memory of this very cool, unusual experience just kind of like breaks up the monotony of your life for a little bit? And does it even matter? I don't know. Yeah, I don't know. I mean, I think that what's so what I find so compelling about this is like, I could not tell you right now. Now that's not true. I could tell you. But like, if I think about like, what is the single most like unusual and meaningful experience of my life?

54:39It is having, it is birth of my children. Like the experience of like producing a new person, it was not comfortable. It wasn't like a, you know, which I think is also true, but like, it was a very unusual experience that I still could, I could tell you almost to the minute in both of the births, like exactly what happened.

54:57Emily Oster:Because your salience system was revved So high. And I could tell you who was in the room at each of these moments, exactly what happened. And so I'm so curious about, I find this whole thing very curious. I'd be interested to have an experience like that where you didn't also have to push a person out of your vagina, which has some negatives in the long run. And I mean, positives also. You wouldn't be worried that it would push the meaningfulness of those experiences down, right? You'd be like, yes, the birth of my children was the second most important thing that ever happened to me. The second and third.

55:34I mean, I'd have to like break them.

55:36Emily Oster:Like staring at the wall for three hours. Relative to lying here. Sorry, Emily's kids. You're not that replaceable, I promise. Yeah, sorry, kiddos. All right. Two other things before we end, I think we should touch on. So one is I hear a fair amount about micro dosing, but my read, which is like, maybe I take a little bit of mushrooms every single day to improve some aspect of well-being. My read is actually people have tried a little bit of this and it doesn't work. Yeah. The studies of micro and micro doses, you know, first of all, there's no great definition of this. Like in theory, a micro dose should be a dose low enough that you don't experience the psychedelic effects.

56:18Emily Oster:Like you're not supposed to feel much if you're really micro dosing. And I'm not sure that's how people are doing it. Right. It's like I'm microdosing wine by only drinking a glass. Like, well, that's not really. But yeah, the studies that have looked at microdosing, my read is that it does show some improvement in well-being on the day people microdose, but it doesn't persist to the next day. And it certainly doesn't persist in the long term, which also feels like drinking a glass of wine to me. So maybe that's what it is. yeah maybe or maybe it's just a placebo effect it could definitely be a placebo effect which is also what a glass of wine is to some extent there are some safety concerns we should run through uh people who are schizophrenic should not use these medications they're also illegal they're illegal uh oh yeah so that's i have to say as i was reading all this stuff and especially about the healthy 40 somethings and it being this incredibly meaningful experience i was like you know, I'm curious, like I would probably want to try.

57:25And then I'm like, oh, I have literally

57:27Emily Oster:no idea like how to obtain a psychedelic, like short. Have you been to a fish concert? Have you been to a fish concert? Do they still exist? That's the that's the I think that that relates to the second point, which is, of course, like these drugs are illegal. And so if you decided you're just going to go out and like get yourself some, you know, psilocybin on the on the street corner and like do it, do it yourself. You don't know that that's what it, what it is. And so, you know, please do not, do not do that. Yes. Adulterated stuff, particularly, I mean, I guess mushrooms kind of look like mushrooms, but first of all, mushrooms are very scary because some mushrooms look like other mushrooms and some are toxic.

58:08Emily Oster:So there's mushrooms. Don't eat mushrooms. And, and then LSD is so potent. Like an amount of LSD, the size of a grain of table salt is a real dose of LSD. It is a thousand times more potent than psilocybin at the serotonin 2A receptor. So that's fine if it's being like synthesized and careful and everything is proper, but like it does mean that you can't inspect it. Like you're trusting that whatever's not like dissolved on this piece of paper you're putting on your tongue is what people tell you it is. And yes, things absolutely get adulterated. So be careful out there. The psychedelics increase blood pressure a little bit.

58:47Emily Oster:We should say that, you know, whatever, if you have blood pressure problems, be aware of that. And then, yeah, you want to be in a safe place. You're not going to be operating vehicles, folks. You got to be careful. You got to be careful. All right, Perry, smash or pass on the psychedelics? I'm smashing psychedelics. I mean, as someone, again, as someone who's never done them, I think that the data for mental health is highly compelling. Obviously, I want to see more research here, but I'm so excited that that is potentially opening up, that a new door is opening for people who suffer from these conditions.

59:24Emily Oster:Super exciting. In terms of general wellness, I'm mostly curious. I don't certainly think it would ever become part of my wellness routine, but am I going to die never having experienced the single most unusual conscious state of my life? That doesn't seem like a good idea. Emily, smash or pass. I am also a smash on this. I think I'd like to wait until it gets a little more regularized. Or regulated, so you know that you're getting a safe amount or something. Yes. But I think definitely, I feel like when we were in college, pot was illegal, But now there's a drive-through dispensary on the highway.

1:00:12And I feel that when there is a drive-through psilocybin treatment option, I'm going to do it.

1:00:21Emily Oster:And when that happens, should we do an entire Wellness Actually episode? About what happened and the different goblins and so on? I'm saying during. During, not after. Okay. I think these things are like 10 hours long. I'm not sure that people's case for us is then. Livestream. But we can edit it. We can edit it down. Sounds great. Your question of the week after the break. Let's take a minute to unpack the myths behind GLP-1 drugs. Myth number one, GLP-1 is a long-term solution for weight loss. True. True. GLP-1 can potentially be a long-term solution for weight loss if you want to be on a drug that changes your body's natural instincts.

1:01:05Myth number two. GLP-1 can fix your metabolism. False. GLP-1s fix hunger, and this leads to weight loss. But the GLP-1s may actually slow down your metabolic rate as your body adjusts to consuming fewer calories. Myth number three. GLP-1 leads to a loss of muscle mass. True, GLP-1 can lead to a loss of muscle mass due to losing weight so rapidly that your body is pulling from both fat and muscle to make up for the energy gap from consuming so few calories. If you're looking for a natural GLP-1 therapy, you should consider Metabolism Ignite. Metabolism Ignite is powered by plants and can help boost your natural GLP-1.

1:01:41Visit veracityhealth.co to learn more. That's V-E-R-A-C-I-T-Y health.co and type in promo code IHEART for up to 65 % off your purchase. Apple Vacations, where your story starts.

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1:03:25Hi, I'm Alian Perry. This is Meredith in Phoenix. And I have kind of a love-hate relationship with tracking, you know, calories and steps and sleep. I think I'll love it and then I get kind of obsessed with it and then I hate it. So I have a question for you. What is your relationship with tracking? What do you guys each track? Thanks. All right, Perry, I would venture this is a place in which we are almost polar opposites for people who otherwise share like a pretty similar like demographic lifestyle? Like you don't do any self-tracking, do you?

1:04:05Emily Oster:I'm really trying to think here. What do I track on like a daily basis? Like, I've been tracking our podcast rankings. So hey, everyone, leave a review and give us five stars on Apple Podcasts to help my daily tracking. No, I don't weigh myself daily. I think my phone tracks my steps, but like, I don't know what they are. I don't track calories. Yeah, I am not a tracker. But Emily, how many different spreadsheets do you use to track? It's not zero. I'm just going to say it's not zero. I track a lot of things and I want to explain why, because I generally don't think it's a good idea. I feel like this is a like, don't do, like do as I say, that as I do, I think for almost no one, is it a good idea to obsessively track a huge number of the things that you're doing?

1:05:02Because I think for a lot of people, it makes it very anxious. Yeah, yeah, yeah. People always tell me like, okay, I'm tracking my sleep. But like, I woke up this morning and my sleep tracker said I didn't sleep good, but I felt like slept good. And now I'm like worried. Now I'm laying up a night worrying my sleep tracker is going to judge me for my like lack of sleep. And that's really bad for your for your sleep. So I think for most people, this, there is like no, people don't like it. It makes them anxious and there's not a lot of value. Like if you just said like, I'm interested in like improving my health.

1:05:33Yeah. For the most part, like you don't need to do any tracking for that. Um, why do I do this then given, I want to know what you do.

1:05:41Emily Oster:Give me like what the thing is that you track. So I have a whoop, which tracks my sleep and my recovery. I track the miles that I run and the workouts that I do. I track how much protein I get. Sometimes I track other macronutrients. Right now I'm doing that because I wasn't eating enough and now I need to eat more for, so I'm tracking my macronutrients. And that's probably it. Okay. All right. Yeah. That's not bad. So it's a lot of different things. But I will say the two reasons I do this, other than being crazy, which is I guess the third reason, is that I really like it. It's like a thing I enjoy.

1:06:27You're an economist after all. But it's like I like it. It's fun. You're a numbers person. I'm a numbers person. I like data. I track when my kids were babies. We would like track the diapers and the amount of time they slept and all kinds of other stuff. because like even though I realized it was useless, I just like thought it was fun. Yeah. And I care, as have previously mentioned 400 times on every episode of this podcast, I care tremendously about my athletic performance. And a fair amount of the tracking I do is in the service of like, like trying to link like behaviors to performance outcomes.

1:07:03Right. So that's it. But I don't think other, I'm not, maybe I'm just saying other people shouldn't do this so I can run faster than them. Perhaps that's, this is a competitive advantage.

1:07:12Emily Oster:I would not put it past you. All right, that's it for us today. Stick with us next week when we'll ask, what's the deal with methylene blue?

1:07:26Wellness Actually is produced in association with iHeart Media. Our senior producer is Tamar Avishai. Our executive producer at iHeart is Jennifer Bassett. Our theme music is by Eric Deutsch. and our content is for educational purposes only.

1:07:40Emily Oster:If you like the show, help other people find us. Leave a rating and review on Apple Podcasts or your podcatcher of choice and help us spread the word about the show. You can follow us on Instagram at wellnessactuallypod. And don't forget, we want to hear from you. Head over to wellnessactually.fm and leave us a question for our mailbag or suggest a topic for a future show. We'll let the influencers have the last word. We found this one swimming naked in the fermentarium. I am the Lizard Queen!

1:08:22Let's take a minute to unpack the myths behind GLP-1 drugs. Myth number one, GLP-1 is a long-term solution for weight loss. True. GLP-1 can potentially be a long-term solution for weight loss if you want to be on a drug that changes your body's natural instincts. Myth number two. GLP-1 can fix your metabolism. False. GLP-1s fix hunger, and this leads to weight loss. But the GLP-1s may actually slow down your metabolic rate as your body adjusts to consuming fewer calories. Myth number three. GLP-1 leads to a loss of muscle mass. True. GLP-1 can lead to a loss of muscle mass due to losing weight so rapidly that your body is pulling from both fat and muscle to make up for the energy gap from consuming so few calories.

1:09:04If you're looking for a natural GLP-1 therapy, you should consider Metabolism Ignite. Metabolism Ignite is powered by plants and can help boost your natural GLP-1. Visit veracityhealth.co to learn more. That's V-E-R-A-C-I-T-Y health.co and type in promo code IHEART for up to 65 % off your purchase.

1:09:27Emily Oster:Apple Vacations semi-annual sale is here, and it's the perfect time to plan your next beach getaway. Enjoy up to$250 off international and Hawaii vacations, up to$150 off domestic trips and hotel savings up to 70 % off. With instant savings of$300,$500, or even$700, your escape has never been more rewarding. Book by May 28th at AppleVacations.com or contact your local travel advisor. Apple Vacations, where your story starts. Paramount Plus is now the home of all your BET favorites. What? Yeah! With all new episodes of Tyler Perry's Divorce Sisters. You've always liked a little drama. Plus a whole new world of movies like Gladiator 2.

1:10:06Emily Oster:Now I will control an empire. Original series like The Chi. Just make sure we protect each other. And live sports like UFC. Welcome to the history books! New home, same family. Your BET favorites are now on Paramount Plus. Subscribe now. This is an iHeart Podcast. Guaranteed human.