The future of sleep
Neurobiologist Jamie Zeitzer is an expert on sleep – or, more accurately, an expert on why so many can’t sleep.
He notes that, ironically, it’s often anxiety about sleep that prevents good sleep. In short, we lose sleep over lost sleep. Wearables and other tools can help but only to a point, and medications do not induce natural sleep. Instead, he counsels consistent routines, less stimulation at bedtime, and cognitive behavioral therapy to reduce worry about insomnia. Unfortunately, you can’t work harder to get better sleep – you have to learn to relax, Zeitzer tells host Russ Altman on this episode of Stanford Engineering’s The Future of Everything podcast.
Transcript
[00:00:00] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. I thought it would be good to revisit the original intent of this show. In 2017, when we started, we wanted to create a forum to dive into and discuss the motivations and the research that my colleagues do across the campus in science, technology, engineering, medicine, and other topics. Stanford University and all universities, for the most part, have a long history of doing important work that impacts the world. And it's a joy to share with you how this work is motivated by humans who are working hard to create a better future for everybody. In that spirit, I hope you will walk away from every episode with a deeper understanding of the work that's in progress here, and that you'll share it with your friends, family, neighbors, coworkers as well.
[00:00:48] Jamie Zeitzer: Is your cognition as good if you don't get enough sleep? No. Is your memory as good? No. Is your metabolism as good? No. But all those pale in comparison to the fact that you feel tired. And so, you know, what is sleep doing? Well, it's doing a lot of things. You know, I, I think that there's no singular thing that it does. It basically, it prepares us for being awake.
[00:01:12] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. If you're enjoying the show, if it's helped you in any way, please consider sharing it with friends, families, and colleagues. Personal recommendations are a great way to spread news about the podcast and help us grow today. Jamie Zeitzer will tell us about sleep. He'll tell us that one of the big problems if you're having trouble with your sleep is worrying about it. He has some hints about how to loosen up, worry less, and sleep more. It's the future of sleep. Before we get started, a reminder to please tell your friends, family, colleagues, acquaintances, anybody you know, and like, that they should listen to The Future of Everything podcast. Spreading the word is the way to go.
[00:02:01] Well, we all know about sleep. We all know that it's critical. We know that it's annoying not to get enough sleep, and it's great to get a good night's sleep. But the frequency of folks who have trouble with sleeping is remarkable. One of the things that they do is they worry about their sleep. We're gonna find out that worrying about your sleep is a great way to make sure that you don't get great sleep. But what about medications? What about wearables? My watch can tell me how well I slept last night, but guess what? I kind of already know. Well, Jamie Zeitzer is a professor of psychiatry and behavioral sciences at Stanford University. He's an expert at circadian rhythms, bad sleep, good sleep, and how to optimize sleep. He's gonna tell us that wearables don't work. There are some medications that sound pretty promising. And don't worry about it as much as you are, because that's contributing to the problem.
[00:02:51] Jamie, what made you decide to devote your professional life to the study of sleep?
[00:02:57] Jamie Zeitzer: Probably the, uh, the, the old adage of, you know, physician help by self. Never been a good sleeper, always had problems, um, actually came in through a, through a back door. I, I, I was trained in circadian rhythms. But found that sleep paid the bills better. So,
[00:03:12] Russ Altman: Okay. Well that leads right to what I wanted to ask you about, which is two things. Why do we sleep and how is it related to our circadian rhythms? And maybe even, maybe you should define, for those who haven't thought about circadian rhythms very much, uh, what are they and how do they relate to sleep?
[00:03:29] Jamie Zeitzer: Sure. So circadian clock, so I didn't hear about until graduate school. So if, if people haven't heard about it, that that's okay though, though it is definitely more, more out there right now. I, these are intrinsic twenty-four hour rhythms. Um, I find them particularly appealing. They, they are endogenous to an organism and you find them in every single organism that has ever been studied on the planet Earth. So there's obviously something incredibly important about them if throughout the evolutionary tree you see them. And, and these are basically the, the key to these rhythms is that they allow you to anticipate changes in the future. So as opposed to responding to the environment, you can anticipate them. And so one of the obviously anticipations that, that we have as humans is sleep. And so it's very much intimately involved in the timing of sleep, when we sleep and how we sleep.
[00:04:13] Russ Altman: So it sounds like, um, from what you're saying, I'm, I'm, I'm kind of, um, it's kind of implying to me that circadian rhythms might have lots of other uses to the organism other than, uh, telling us when to go to sleep and when to wake up.
[00:04:27] Jamie Zeitzer: Absolutely. They're, they're, they're basically involved in, in pretty much any physiologic process. I mean, the, the vast majority of them have a circadian component. The real question is what is the magnitude of that component? Not if it, and, and in fact when people show like, oh, there's no circadian component, I'm like, wow, that's really important because it means that you have to be up all the time. There's no anticipation, uh, for it. And so everything, you know, if you look at immune system, if you look at breathing, heart, you know, diet, every, every aspect of your physiology, there's a circadian component.
[00:04:57] Russ Altman: Okay, great. Okay, so, and now, and now let's go to sleep. Um, and I kind of buried it, but like, do we understand why we sleep and why it's critical?
[00:05:06] Jamie Zeitzer: No.
[00:05:07] Russ Altman: Okay. Thanks very much. That was Jamie's answer.
[00:05:10] Jamie Zeitzer: There you go. Um, so I mean, you know, we, we have ideas about what happens during sleep. Um, you know, what exactly, why is it important? I mean, by far, if you take a look by far the biggest effect size about losing sleep as you feel tired. And, and it's not even, I mean, it's, it's more than tenfold, bigger than any other like cognitive effect. Like basically is your cognition as good if you don't get enough sleep? No. Is your memory as good? No. Is your metabolism as good? No. But all those pale in comparison to the fact that you feel tired. Um, and so, you know, what is sleep doing? Well, it's doing a lot of things. You know, I, I think that there's no singular thing that it does. It basically, it prepares us for being awake. And anything that can be optimized during sleep while we're not, you know, while we're not awake and gathering information, that that's kind of what happens there.
[00:06:00] Russ Altman: So, so you said earlier that part of the reason you entered the field is, you know, you, you've been, you have problematic sleep and we'll, I, I want to get into that. Well, perhaps not your personal sleep situation, but the issue. And, but I will also just disclose that I feel very lucky to be, um, I don't know what the word would be, but gifted would be the only thing I can think of. And it's been a incredible asset to my life. Uh, when I get nervous about things, I actually go to sleep instead of like staying awake. And it was extremely adaptive, like as a student and whatnot. Okay, enough of the biography. Um, I know you've studied a lot about light and, and there's a sense that we all have that the circadian rhythm in some sense is, um, kind of synchronized with the Sun. And so tell me about the role of light, and particularly in sleep.
[00:06:45] Jamie Zeitzer: Sure. So where the, so the circadian clock in humans on average is a little longer than twenty-four hours, around twenty-four point two hours. So it has to synchronize to a twenty-four hour day. How does it do that? Mainly through light. And so basically your light exposure is dictating where the circadian clock is placed. The most, you know, obvious place that you experience this is when you travel across time zones. You go into a new time zone. How do you adapt your internal clock to the external time that you're living on? That's through light exposure. So the light exposure is basically dictating where this circadian clock is positioned. And therefore where, when you're sleeping, when you feel tired, when you feel alert.
[00:07:22] Russ Altman: And, and is it certain, is it sunlight? Is that what we need? Are there certain waves of light? I know you've looked at flashing lights. This is all very interesting.
[00:07:30] Jamie Zeitzer: Yeah. So you know, basically anything you can see can impact the clock. And it's just a question of magnitude. Um, if you are completely optimized, so you've been in a dark environment for a long time, even fairly dim light, just like a few candles worth of light can impact the clock. But in general, in, in most adult humans, um, you, you're talking about room light being effective and outdoor light being about twice as effective, even though outdoor light is more than tenfold brighter, there's a compression of this information. So, but that being said, room light, it's about half as important as outdoor light. So even what you're getting in a standard, you know, office environment, home environment can be very impactful.
[00:08:13] Russ Altman: And, and, and does that have any implication for like, uh, optimal, so, uh, uh, I think of room light as a little bit more orange, a little bit on the red side of the spectrum. I think of sunlight outside as a little bit more blue. Um, is, does that imply if we're spending time, you know, a lot of us are in offices, we don't get to go be outside all day. Um, does that make implications for what kind of lighting we should or should not be using, uh, in our internal environments?
[00:08:41] Jamie Zeitzer: Yeah, so the, the circadian clock is definitely optimally, um, sensitive to the shorter wavelengths, blue light. Um, and that's because basically how, how light information goes from the outside into the circadian clock, um, is a combination of your rods and cones, which again, you see things with which are more optimized in, in TOTO to green light. Um, but then it also uses this substance called melanopsin, um, which is a opsin, it's, it's basically, it's a protein in the eye that can also respond to light, and that's blue sensitive. So this is why when you hear a lot about blue light, that's the kind of the concern. Now again, any light can have an impact, but blue light photon for photon is more impactful. So, when you're inside, the real thing about being inside and again, after the pandemic, so many people working from home, um, the real thing is that you need to create a contrast, right? So, so basically the brain is, and circadian clock is really good at, at adapting to your light level.
[00:09:43] So even if you were, say, living in a cave all day, if you had five minutes of light. That'd be totally fine, right? But you need a contrast. You need dark and you need light. And so if you're basically inside all day in an office and then you're, it's a home office and you're into the same lighting throughout the evening, there's no contrast. It didn't know that that was day and that this is night. And so the, really the thing that people have to pay attention to in terms of working from home, things like that, is that they have to create this contrast. And that contrast might be, uh, have better lighting in, in your office. So basically brighter lighting. I mean, we found that even if you just increase the brightness of, of your lighting during the day, uh, in your home office, that's sufficient. Or go outside, which is good for number of reasons.
[00:10:31] Russ Altman: Reasons, yes.
[00:10:32] Jamie Zeitzer: You know, but, you know, go outside for a half hour in the afternoon, like three o'clock in the afternoon, ideal time to go outside, you get the light there. And the other thing that that does is that it also minimizes the impact of light in the evening. So the light, how the, how the clock responds to light as well as many other kind of, um, impacts in the brain, it's, it's a relative thing. So it's not just looking at how bright it is, it's how bright it is compared to what you were getting before. So if you're inside all day, there's no contrast. If you go outside for a half hour in the middle of the day, you get well, nice California weather. We're getting eighty-thousand lux outside. You come back inside and you get fifty lux, all of a sudden that fifty lux isn't so bright. But if you were getting fifty lux all day and then you're getting fifty lux in the evening, that appears brighter to the system.
[00:11:18] Russ Altman: Okay, so I do want to go to, to the issue of people who are having problems with sleep. Um, and, and, and I think it's gonna be related to a lot of these things and there's, you know, we were all, we're all getting advice about, you know, if you're looking at your phone at midnight, you should be looking at your phone with an orange light and not with a blue light. And I don't even know if you want to comment on that at this point.
[00:11:39] Jamie Zeitzer: Oh, sure. No, absolutely it, a lot of things do, but this particularly drives me nuts. Um, so if you are, again, inside all day long, don't get any bright light, can that light from your phone impact your brain. Sure. Absolutely. I mean, physiologically speaking, you keep someone dim light all day and then you give 'em a phone at night, it will impact it. The vast majority of people though, don't do that, right? They're getting any degree of, of light that would really minimize that light. So the problem is that when, when you say, oh, I've got this orange filter on, on, on my, on my phone, now I can do whatever I want. It's like, no, it's like you're doing things like you're checking your email, which is stressing you out, or you're on an app that has been optimized by psychologists to keep you on the app. You know, I've got this great clip that I love playing for classes here, which is of Reed Hastings, who's the, um, CEO of Netflix and during a corporate earnings call, and this was several years ago. He said, our biggest competitor is sleep.
[00:12:38] Russ Altman: Oh my goodness.
[00:12:38] Jamie Zeitzer: And, and he wasn't kidding. It's 'cause you got the next episode button and you just keep, next episode, next episode, next. And so you don't, you know, you don't pay attention to sleep. So blue light, light filters on phone, do they work? Yes. If, if you're inside all day, they, they, they're nice. But by far the much bigger thing is the content, what you're experiencing, how it's impacting you. If you're checking something out, you know, and you're stressing out like, oh my god, everyone else is having so much fun, I'm not having fun. Yeah, that's gonna keep you awake. Or, oh, look at all this work I have to do. It's gonna keep you awake. Um, ah, politics. Wow. Yeah. That's definitely gonna keep you awake.
[00:13:16] Russ Altman: Right, right. So perhaps the blue, orange thing is in the noise of all the other stuff that's happening.
[00:13:22] Jamie Zeitzer: It, it, when you look at the effect size, it's not even close. I mean, the only good thing that, that it really does is that it provides kind of like an inverse alarm clock. It reminds you it's time to go to bed. Like, when your screen automatically changes color, you're like, oh yeah, it's, it's, it's, you know, eleven o'clock at night, it's time for me to go to bed. I didn't, I lost track of time. So in that sense it can be a, a helpful psychological cue, but in terms of its actual effects in the brain, it's really doing quite, quite little.
[00:13:49] Russ Altman: Okay. So let's go to problems with sleeping. Uh, it is so common, like, uh, it's the number I'm aware of it 'cause as I said, I don't have problems and so I'm maybe sensitive to hearing how many people are struggling with it. Uh, it's a topic of conversation. Um, what can you say about it? Like what are the sources of this? What it, what I am impressed by is when you, as a, I'm a doctor, I can ask somebody, how's your sleep? I do not have to explain what it means. They know if it's good or bad or, or middling. And so tell me about sleep problems and how we should think about them.
[00:14:24] Jamie Zeitzer: Yeah. So it's good that, uh, uh, as an MD you actually ask people that question because most MDs do not want to ask that question 'cause then they'll get an answer and they don't know what to do, right? So, um, then, oh, I gotta document that, so.
[00:14:38] Russ Altman: And Doc, can I have a pill please?
[00:14:40] Jamie Zeitzer: Exactly, 'cause that's what people want. I mean, they, they just want, they, they want an on off switch. Um, we don't have that. There's, so there's been a lot of concern about sleep there, there's been a lot of, um, there have been many things published in the, in the lay press books telling us how terrible it is to lose sleep. I, I don't happen to agree, now, I'm not saying that the data are wrong, but I, I don't happen to agree that scaring people into getting more sleep is actually an effective way of getting them more sleep. What it does, it makes them more anxious about their sleep. And the only thing worse about not getting enough sleep, is not getting enough sleep and being anxious about it.
[00:15:20] Like, that's worse. I mean, the, the, the stress that you're experiencing, that's doing far more damage. Honestly, losing the night of sleep or not getting great sleep, it's more like a lottery ticket. Very long odds, and you're talking about, like you, you telling someone who's twenty-five years old, you know what, you should get better sleep because in thirty years if you don't get good sleep now, you're gonna have like a three percent increased risk of getting diabetes. I mean, it's stupid. I mean, that's not gonna actually change people's behaviors. So there's a lot of anxiety and that's, that's, that's causing problems. Um, we can talk about wearables. They don't work. Um, they're not accurate.
[00:16:02] Russ Altman: Well, wow. Okay. So yeah, you went right to the wearables and like you know, my watch every morning is telling me exactly how much time I spent in each of these phases that I don't really understand, but it, but it's, it's very impressive.
[00:16:17] Jamie Zeitzer: Yes. It's, it's nice, but it's, if you're, in you, it's probably actually reasonably accurate. In bad sleepers, it's completely inaccurate. And, and there are a number of reasons for that. And, but the biggest problem is that even if it were a hundred percent accurate in everybody, it's decontextualized information. It makes people anxious about their sleep. Especially if, look, if they're getting good sleep, fine, great. But if you're getting bad sleep and it's, and it's accurately saying, well, you didn't sleep well last night. You know, you didn't get a lot of deep sleep, you got too much N1 sleep. What am I gonna do about that? Like, now you just make me anxious. Like, before I just woke up and I was tired. Now I'm waking up, and now I'm anxious. Um, so it's not particularly helpful. Um, and, and that's something, uh, you know, that I, I hope in the future basically, this is one of the things that I think that we need to get to, is not only making that data accurate in people who are bad sleepers, but also then contextualizing it in terms of what you can do about it.
[00:17:14] Russ Altman: Yeah. Actionability is always kind of, um, on, on, that's what a, that's what the physicians would want. That's why they would, they would ask more if they had a toolkit to actually be helpful.
[00:17:25] Jamie Zeitzer: Exactly, and look, now there are, there are standard kind of, uh, interventions that work quite well. Um, CBTI, cognitive behavioral therapy for insomnia, works really well if people are willing to do it. It's not talk therapy, it's not, you know, like how your mom screwed up your sleep in your entire life kind of thing. It's, this is more on like, okay, um, you know, here are some tools that you can use to get sleep better. And the amazing thing about it's when you look at the objective measures of sleep and someone who's been successfully treated, like they had bad insomnia, and now they say they're fine. Their objective measures of sleep really don't change that much.
[00:18:01] What changes is their perception. They basically, you teach them not to care about their sleep so much. And so if it takes you, for example, if it takes you a half hour to fall asleep, that would be considered a long time. But if it doesn't bother you, that's not insomnia. Clinical definition of insomnia and all of the, you know, the, the, the international definitions, no numbers, right? So it's not about how long it takes you to sleep. If it takes you ten minutes to fall asleep, which is totally normal, but you're anxious about that, that's insomnia.
[00:18:31] Russ Altman: Okay. So there's a functional element to these diagnoses, which actually sounds like the right answer.
[00:18:37] Jamie Zeitzer: Yeah, I mean, so it's basically saying like, if it doesn't bother you, okay. You know, and, and really there's, there's been a move, you know, people have for a long time really kind of dichotomized sleep. You have good sleep or bad sleep, you know? Um, now we understand that there's, there are people with good sleep and there, and there are people with pathologically bad sleep, but it's a bell curve and there are different components. Duration is just one of them. You know how, how regularly you go to sleep, like if you, you might have, like when we study college students, uh, they're wonderful to study. Because, um, I, I, I often, when, when I, when I lecture to them, I'll thank them because I, I say because you do things to your sleep that we study that ethically we're not allowed to ask you to do.
[00:19:19] Russ Altman: I was gonna say, the ethics board would never let us do what you do to yourself.
[00:19:24] Jamie Zeitzer: No, in a million years. It's like, so what I want you to do is sleep three hours tonight, but go to sleep at two AM. Then tomorrow night I want you to not sleep at all, and then the next night I want you to go to sleep five hours earlier, but sleep ten hours. It's like, you can't do that. Like there's all sorts of data saying how bad that is for you, but people do this. So, you know, and they very rarely have, you know, insomnia. I mean, many, you know, there are many college students who do. But they're usually so sleep deprived, there's, there's no insomnia. I mean, we in fact, have studied, in the past, we, we did a, a modeling study looking at the impact of caffeine and basically found that for most college students, caffeine has no impact. Like they're having like six hundred milligrams of caffeine right before they go to bed and fall asleep instantly because they're so sleep deprived.
[00:20:08] Russ Altman: Yes. My daughter is a, uh, resident, she's a medical resident and she's had sleep problems in the past per her own report. But I asked her about her sleep during a residency and she said, that has gone away, dad. If I see a bed, I'm asleep.
[00:20:22] Jamie Zeitzer: See, there you go. This is where gurneys all of a sudden look like comfortable, uh, you know, sleeping positions.
[00:20:27] Russ Altman: This is The Future of Everything with Russ Altman. More with Jamie Zeitzer next. Welcome back to The Future of Everything. I'm Russ Altman and I'm speaking with Jamie Zeitzer. In the last segment, we talked about some of the basics of circadian rhythm, sleep problems, and worry. In this segment, we're gonna touch upon medications and we're gonna talk about some easy do's and don'ts that can help you improve your sleep if you're not happy with it.
[00:21:01] We were just talking about these college students that you talked to and the fact that you can kind of, my words, not yours, you could hardly pay them to have more bizarre sleep habits. So what, what kind of things do we learn from, from, from those students and, and teenagers and people who are at the extremes of like, testing their sleep, sleep ability.
[00:21:21] Jamie Zeitzer: Yeah. So we, we use it to our advantage. Basically, what we do is we, when they have these kind of weird schedules, we're able to then look and see what is the contribution of circadian rhythms and what is the contribution of sleep. So in normal humans that are regular sleepers at all, when your circadian clock is timed, is almost always at the same time relative to sleep. Like it's always signaling for sleep when you're asleep. In college students sometimes it's signaling for sleep when they're awake, sometimes signaling awake when they're asleep. So basically, it's called basically a desynchronization of these two systems. So it basically gives us an opportunity to study what the contribution of this. So for example, where right now we're just finishing up a study where we're looking at how sleep and circadian rhythms in the menstrual cycle impact, um, injury risk in college aged women. Uh, and so basically these have been studied independently, but these are not independent factors. So the question is, well, can we use this and kind of tease it apart? So we're using it basically as kind of a scientific tool.
[00:22:24] Russ Altman: Yeah.
[00:22:24] Jamie Zeitzer: Now, of course it would be great if they slept better, but, you know, students are busy, they've got fun lives, there's interesting things. And so we're, we're, we're letting them do that. And then trying to figure out like how, how to adapt afterwards.
[00:22:36] Russ Altman: Really interesting. So, um, it, that made me think that, is it something about college or is it that age group? So if I look across the world at people in that age range, let's say eighteen to twenty-two, are they kind of always a little bit, um, wacky with their sleep? Or is this a phenomenon about the college?
[00:22:56] Jamie Zeitzer: I think it's a combination. I, I think at that age, basically you have the, the independence to do this kind of stuff, um, and you also have the recovery. You know, as, as I, as I tell my younger students, like, it's not that I can't do it anymore, it's that I, I can't do it anymore, like every night, you know? You know, I, I can't stay up until three o'clock every single night. I can do it every once in a while, and then it kills me for a week. But they can do it and then just like roll outta bed the next day fine. So their recovery is, is remarkable. So basically they can do it and it's fun. And you know, I think it's at a time of life, especially in college, but even if you're not in college, even if you're working where there's a lot going on. You know, you're exploring a lot who you are, various kinds of interests, things like that. So, um, and then it's unique to the college. But I, I do think that it definitely accentuates this, it gives you kind of a protected realm to, uh, to kind of do this and, you know, and occasionally study and things like that.
[00:23:49] Russ Altman: So, so what about folks who are, uh, you know, they go, they grow older and they're, they're involved in shift work, they have shifts, you know, nurses, we, we all know the kinds of folks who do that. That must, that's a big deal for them, I'm, I'm guessing. And, um, how do they manage it? And what do you learn from looking at, at their, uh, do they just switch their circadian clocks or is it more complicated than that?
[00:24:09] Jamie Zeitzer: Yeah. So they, they, they try to, but they can't. So basically what happens is we have the technology to, to flip people's clocks. We can make night people or day people night, night people day. Not a problem, but it takes time.
[00:24:20] Russ Altman: Let's put a pin in that, 'cause I, we want to hear about that for sure.
[00:24:23] Jamie Zeitzer: Yeah. So, but, but it takes time, you know, it'll take like a week. So if you're on permanent night shift, you can totally do that. But the problem is that people who are on permanent night shift, then on their days off are day shift. They wanna be awake during the day, see family and friends. So we don't have the ability to flip people back and forth, let alone what is more common in shift work, which was is people kind of flipping back and forth on multiple different days, um, so they end up basically getting meh sleep all the time. And then being tired a lot. So we try to work with them, things like taking naps, prophylactic naps. So basically nap before you go on a night shift. Um, actually a lot of the older nurses that we've worked with, you know, they enjoy that.
[00:25:05] My, my wife, she's a hospitalist, right? Pediatric hospitalist. And so I think it's basically to directly insult my profession, um, because she's worked twenty-six hour shifts for the past twenty years. Um, and, but she likes it because it gives her a flexibility in terms of her schedule and being able to, you know, she was able to be with the kids when they were younger, uh, and now when they're a little older, you know, to be able to see them after school. So, it gives them certain flexibility. Other people are on, on shifts because they have to, it's economic necessity. They don't wanna be on shifts. But they have to. And it's, it's difficult to do this, it's difficult to sleep during the day, you know, we can do that. We've got medication that we've tested, we've shown that we can take people who are shift workers and um, and basically have them in, in the wild.
[00:25:53] So, so they're doing what they do. They normally sleep around four hours and we can give them medication that basically suppresses a wake promoting signal, uh, which is hypocretin, uh, and basically suppresses this signal. And hypocretin is something that, you know, if you, if you don't have it, you have narcolepsy. Um, but you can suppress the signal. It doesn't do much else. And humans accept this wake promoting signal. So when you suppress that, they go from getting four hours of sleep to getting six to seven hours of sleep. So you can totally get that if you're willing to take a medication during the day. If you're not willing to take a medication, it's really hard to get more than four hours during the day.
[00:26:26] Russ Altman: Okay. So you, you said the word medication. I know everybody is interested in this. So talk to us, you know, we, we know about benzodiazepines like Valium and uh, and uh, we know, so tell us what the status is and does any of this work? Is any of it look promising to you? Uh, where are we?
[00:26:43] Jamie Zeitzer: So benzodiazepines work great if you don't wanna be awake. They don't recapitulate normal sleep. But for most people, for short term, your dog just died, you're totally stressed. You can't sleep. A benzodiazepine does exactly what you want, which is it puts you into a state of not being awake, right? So that's fine. I, I totally see how that works. And I, I support that and, and I think it's a great kind of medication to basically anesthetize people, put them, you know, into a state of not being awake.
[00:27:14] Russ Altman: So I'm not staring at a ceiling for eight hours.
[00:27:16] Jamie Zeitzer: Right. And anxious and stressed and, and feeling miserable. At least you get some degree of sleep. Again, it's not perfect. It definitely is not the same as normal sleep. So, um, there are many other drugs that have been used for years for sleep. Um, none of them really recapitulate normal sleep very well. Um, using medication for chronic sleep is not a great solution. People use it all the time, though. Um, the most common things that people use are antihistamines. And antihistamines worked well.
[00:27:44] Russ Altman: Benadryl for the kids on the flight to the East Coast.
[00:27:46] Jamie Zeitzer: But you gotta watch out 'cause if they have the hype, if they have the paradoxical hyperactivity,
[00:27:51] Russ Altman: Bad news.
[00:27:52] Jamie Zeitzer: Yeah. So test it out before you go on the plane. But, so I mean, you know, it works, antihistamines work great in the sense that, you know, histamine is awake promoting peptide. You're gonna suppress that wake promoting peptide, which enables normal, normal sleep and that's fantastic. That's what you want. Then you get normal sleep. However, antihistamines are not just antihistaminergic, they're also anticholinergic. So you get a lot of cholinergic side effects. Um, they also obviously work on all histamine receptors, you know, including H1, which are on immune cells. So it's, you know, you take the same drug if you've got hay fever, as you do if you wanna go to sleep. So, it's not ideal. So there are people working on drugs that are going after the H3 receptor, which are auto receptors on the histaminergic neurons in the brain.
[00:28:36] Russ Altman: They would be more specific.
[00:28:38] Jamie Zeitzer: It would be specific just to the brain, would get out the immune effects, they already have ones that are out there for alerting, um, but it's a little trickier to develop an agonist for these receptors, uh, 'cause if you, if you, um, if you basically activate these receptors, you, you're reducing histamine, um, 'cause they're auto receptors. And so basically, so these are, these are great but they're not out there yet. Um, so hopefully, we're hoping that this get out there. There are new drugs that are, uh, that block the hypocretin receptors that we talked about, um, that basically blocks this wake promoting system. Um, they work okay for some insomnia, um, especially if you're trying to go to sleep at the wrong time. So weird thing is your strongest circadian sign for wake occurs right before you normally go to sleep. So if you go to sleep at eleven, it's really hard to go to sleep at ten or nine or eight because the circadian signal is basically keeping you awake, trying to sustain your, your wakefulness, waking day of sixteen hours. It's why if you go from California to New York, you normally go to sleep at eleven, you try to go to sleep eleven, you can't fall asleep. Why? Well, 'cause it's eight o'clock in your brain when you first get there and your circadian system's telling you to be awake.
[00:29:46] Russ Altman: So the circadian system at, at bedtime is more like a cliff. It's not a slow, it's not a slow reduction. It's a, it's, cliff is the right, uh, metaphor.
[00:29:55] Jamie Zeitzer: Absolutely. Yeah. It, it really, you, you've have this, you have this weird window of opportunity for sleep where basically when the circadian system turns off this, this strong alertness signal, which really is a very robust signal and does drop off, as you say, like a cliff, that's your opening of this window to go to sleep. If you spend too long awake after that, the brain's like, oh, Russ, you're trying to stay awake. Let me help you out.
[00:30:20] Russ Altman: Let me help you out.
[00:30:22] Jamie Zeitzer: Let me, let me over ramp all of these systems that shouldn't be up right now. So we're gonna increase norepinephrine, we're gonna increase dopamine, serotonin, let me help you out. And so then you become agitatedly awake. Um, and then it's hard to fall asleep, so it's a window.
[00:30:36] Russ Altman: What about melatonin?
[00:30:39] Jamie Zeitzer: So, open label studies of melatonin, you give melatonin to someone who knows they're taking it at night, thirty minutes up to sixty minutes of extra sleep. Great.
[00:30:49] Russ Altman: Extra sleep. Extra sleep.
[00:30:50] Jamie Zeitzer: Yeah. Yeah. Double blind placebo-controlled trial, five minutes of extra sleep. It's a great placebo. So basically melatonin does not work well at night. It works well during the day, gives you around an extra half hour during the daytime.
[00:31:08] Russ Altman: When you say it works well, the day it, it helps you, like with a nap?
[00:31:12] Jamie Zeitzer: Yeah. Yeah. Helps you with a nap. Or if you're traveling and you're traveling and you wanna sleep, but in, in your body, it's the daytime, then it can work. If you're doing a shift work, and again, you're trying to sleep during your biological daytime, it can work. But at night it really has a very small effect. Um, the other problem with melatonin, of course, is that the dosing, so if you want to get normal physiologic levels, you are looking at three hundred, maybe five hundred micrograms, which is point three to point five milligrams. Of course, you go into the store, and it's really hard to find something that low. It's usually one, three or even ten milligrams, which are super pharmacologic, thousands of times higher than normal levels. And the best part is if you take it at night, not only is it not really gonna help your sleep at night, but the levels are gonna be really high when you wake up in the morning when it's actually gonna be effective. So it's gonna make you tired in the morning. So now when I tell people not to take melatonin if they're using it, no, it's a great placebo. If you basically say, oh, I take this pill and then I can sleep, you've overcome the major barrier to sleep.
[00:32:16] Russ Altman: Yeah. And that makes me think about all your comments earlier about worrying and anxiety, and that's what you're treating.
[00:32:22] Jamie Zeitzer: Yes. Yes, you are now, you, you have basically, you have done something which CBTI tries to train you to do on your own, you have relaxed enough to let sleep happen. Because it's not something that, it's one of the weird things, like you can't actually work harder to get better sleep. You know, when, when I, when I talk to athletes, they're always looking to optimize things.
[00:32:41] Russ Altman: Right, 'cause that's what they do.
[00:32:42] Jamie Zeitzer: Exactly. And they're really good. They optimize their diet, their exercise, their time management. It's fantastic. They try to optimize their sleep and that's awful. I mean, that just does not work.
[00:32:52] Russ Altman: Great. Okay, so in the last minute or so, I, I love to, I'm sure you can do this, tell us, and you've told us already, but it's fine to repeat yourself, somebody who's worried about their sleep what are some of the do's and don'ts that you would tell your friends, your patients, anybody about how to kind of deal with this issue?
[00:33:11] Jamie Zeitzer: So, easier said than done, don't worry. Worry a little but not too much. Again, how, how, how you get to that sweet spot, I don't know. That, that's really hard. And that's actually my, my, my clinician colleagues who do CBTI, they're, they're wonderful at getting you to that spot where again, you're just concerned enough. I mean, to me some of it is, well, a big part of it is regularity. Regularity, not only in the timing of when you try to initiate sleep again, that is great for the circadian clock, um, but also regularity in, in terms of Pavlovian conditioning. You're basically saying, here's what happens, is I brush my teeth, I wash my face, I get into bed, I listen to my podcast, Future of Everything. It's really good. You should listen to it at some point.
[00:33:54] Russ Altman: Very soporific. Let's skip over that.
[00:33:57] Jamie Zeitzer: There you go. And, and, and then I, and then I go to sleep. You know, you set up this routine and it's really helpful. It really helps the brain kind of anticipate like, this is what's gonna happen. Now me, I like doing puzzles. I'll, I'll do like crossword puzzles and things like that because it's engaging enough that it doesn't make me awake but it allows me to be distracted and actually fall asleep. Other people, podcasts, some people do yoga, some people listen to music. It's something which is not gonna stress you out. Like, I love people thinking like, I'm basically, I'm, I'm alpha, I'm up all day. I'm stressed all day, and then I'm gonna turn it off and go to sleep. It's like that, that's not gonna work. You, you, you gotta slow that roll during the day 'cause it's really hard to, to come down. So, it, it's finding whatever is personal to you because there's no one thing that does it. Like, you know, if you like doing breathing exercises, fantastic, you know? That'll work. But so will all of these other things. It's basically whatever calms you down.
[00:34:55] Russ Altman: Alcohol, caffeine?
[00:34:58] Jamie Zeitzer: Um, so a lot of my colleagues are very much against alcohol. Um, to me it's a balance. Like, again, if, it's not good to like have a drink in order to go to sleep, but if there are times when like you're flying and you're anxious and you're taking the overnight flight and having that, you know, that half a glass of wine is gonna help cut the edge and, and like make you not anxious, but then enable you to get sleep. Your sleep's not gonna be as good as it would've been if you could have just fallen asleep naturally. But it's better than not sleeping at all. Caffeine is something that I always caution people to worry about because it's really weird. It's, it's, something that's strange about caffeine because when you look at absolutely healthy people, the half-life range is two to twelve hours, which means that some people have a cup of coffee in the morning and by lunchtime it's all gone.
[00:35:50] Other people have that same cup of coffee in the morning and at night you have half a cup running around your brain. So it's really being aware, and this actually comes in as people get older, you become, your thalamus, your gateway to the brain becomes less able to cut out these signals, right? So it's much easier as you get older, you know, the noise wakes you up now, it used to not. Caffeine will wake you up, it used to not. All of these other things, just being aware of that. So again, caffeine, again, there's nothing wrong with having caffeine. As I told you in college students, they have all this caffeine, doesn't impact them.
[00:36:24] When we look at, uh, soldiers in the military, they're having, I mean, silly amounts of caffeine and they can, you know, and it's totally messing up their sleep. So it's, it's really just being aware, like could that be impacting your sleep, even if it's in the morning. You know, people have shown you give three hundred milligrams of caffeine in the morning and in some people it impacts their sleep at night. So it has the capacity to do so. It's just really being aware of whether you, you know, if you're a fast metabolizer or not. Um, and it's also where, um, actually women on, uh, oral contraceptives actually, it changes the half-life as well. It increases the half-life. So you gotta, you gotta be worried about that too.
[00:37:07] Russ Altman: That's really helpful. And I do know, again, as a physician that people are usually very aware of their caffeine sensitivity. It's something that they've all assayed, they, and so you ask somebody, when's the last time you can have a cup of coffee? And they are calibrated to within half an hour about when that last caffeine can happen.
[00:37:24] Thanks to Jamie Zeitzer. That was the future of sleep. Thank you for tuning into this episode. Don't forget, we have zillions of old episodes in our back catalogs, and you can spend hours and hours listening to them and learning about a wide variety of topics. If you're enjoying the show, please remember to share with your friends, family, colleagues, acquaintances, anybody who you like, tell them because personal recommendations are a great way to spread news about the show and help us grow. You can connect with me on many social media platforms. I'm @RBAltman, or sometimes @RussBAltman on LinkedIn Threads, Bluesky and Mastodon. You can follow Stanford Engineering @StanfordSchoolOfEngineering or @StanfordENG.
