#394 ‒ Sleep pharmacology: the role of medications in healthy sleep, the promise of emerging therapies, and the evidence for common sleep supplements

**Peter Attia** (0:11)
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Welcome to this episode of The Drive. In this episode, I focus on sleep pharmacology. Now, we've had plenty of previous episodes about sleep. We've talked about sleep biology, sleep hygiene, even cognitive behavioral therapy for insomnia or CBTI, and even different sleep supplements. But we've never done anything more than sort of a skim of the surface on sleep medications. And the intention of this episode is to fill that, obviously, very important void.
Sleep is a biological imperative. A pioneer of modern sleep research, first, put the problem this way. If sleep does not serve an absolutely vital function, then it is the biggest mistake the evolutionary process has ever made. When you're asleep, you can't protect yourself from predators, you can't hunt, you can't find a mate, you are, as the phrase goes, dead to the world. But natural selection insisted that we do it anyway. Every single night for our entire lives. That should tell you something. To make this practical, I want to give you a simple way to think about sleep problems, because most people, including most clinicians, don't diagnose them correctly. Almost every sleep issue can be traced back to one or more of four things. First, sleep pressure, that build up of the drive to sleep the longer you're awake. Second, circadian timing, whether your internal clock is aligned with the light-dark cycle. Third, hyperarousal, a state where your brain is effectively holding the gas pedal down when you're trying to sleep. And fourth, sleep architecture, the quality and structure of the sleep you're actually getting. Every tool we're going to talk about, behavioral, psychological or pharmacological, works by acting on one or more of these. And most failures happen when you apply a perfectly good tool to the wrong problem. Few organisms in their natural environment have trouble sleeping. So how did we get to a place where 36% of US adults fail to get the seven hours of sleep that most people need each day for optimal health and functioning? Where more than half of adults report difficulty sleeping and over 22% actually meet diagnostic criteria for insomnia. The answer is that we've engineered an environment that disrupts all four of those systems at the same time. Our sleep is regulated by two processes that were sculpted by over half a billion years of evolutionary experience. The first is the homeostatic process or process S, which is the accumulation of pressure to sleep. Sleep pressure builds as a result of brain activity, though the mechanism for the sleep pressure has not been identified. The longer you're awake, the more it builds until eventually it overwhelms you and you sleep. Think of it like a battery that discharges while you're awake and recharges during sleep. The second process is the circadian process or process C. This is your internal clock anchored to the light dark cycle, coordinated by melatonin at night and cortisol in the morning. It's not just one clock, it's a central clock in the brain with hierarchical peripheral clocks, governing individual cells and organs. We now spend almost all of our time indoors under light that's too dim during the day and too bright at night. We go to bed when our to-do list is finally exhausted, not when our body is biologically ready. We use caffeine to push through the afternoon, alcohol to wind down at night, and then wonder why we sleep like garbage. Jet lag, daylight savings time, and many prescription drugs further disrupt the natural regulators of sleep.
It's our systematic engineering away of these environmental cues that makes sleep a struggle for so many of us. Here's something that might surprise you. Our hunter-gatherer ancestors didn't sleep dramatically more than we do. The data suggest their total sleep time is roughly comparable to ours, and some have even more fragmented sleep.