Sleeping pills may have unexpected effects on the brain

So many of us struggle to fall asleep and stay there through the night. About a third of U.S. adults aren’t sleeping enough. Teenagers’ sleep is even worse; 8 in 10 teens are sleep deprived.

Our collective exhaustion isn’t good for us. Lack of sleep can come with a range of health problems. Our immune systems, hormones, hearts — maybe all the body’s major systems — are influenced by sleep. In the brain, our memory, creativity and ability to learn are, too.

But for something that’s so entwined with our health, the actual jobs of sleep are still, in many ways, a mystery. Scientists have tons of ideas: Perhaps sleep is for rifling through memories, picking out the important ones. Or maybe it’s a quiet, still time for growing bones in children. Or maybe it’s a time to let the brain loose on whatever problem vexed you that day. (One delightfully myopic theory posits that sleep, especially the rapid eye movement stage, is for squeezing fluid around the eye to keep it lubricated.)

Figuring out why we sleep has puzzled scientists for as long as the question has existed. It’s like following hundreds of disappearing breadcrumbs on paths through a forest of trees that keep shifting spots, only to realize you’re standing alone in only your underwear. Oh, and you forgot to study for the test.

Given this hazy scientific landscape, it’s no surprise that efforts to help the sleep-deprived catch some z’s might fall short or have unintended consequences. That’s clear from a new study of the sleep medicine zolpidem.

Zolpidem, sold as Ambien, messes with yet another possible job of sleep – housekeeping. Every 20 seconds or so, a wave of cerebrospinal fluid pulses through a person’s sleeping brain. Scientists suspect that these rhythmic pulses clear out waste products, including the sticky proteins that accumulate in Alzheimer’s disease.

This brain wash is sort of like running the dishwasher overnight, says neuroscientist Maiken Nedergaard, who helped discover the system. Washing up isn’t a flashy job, but an important one that hasn’t been fully appreciated. “The whole housekeeping function of sleep has been ignored for many, many years,” she says.

Mice on zolpidem fell asleep faster and slept deeper than naturally sleeping mice, says Nedergaard, of the University of Rochester in New York and the University of Copenhagen. But they had less power washing, her team reports in the Feb. 6 Cell.

Scientists don’t yet know if this also happens in humans, or what the consequences of this weaker wash cycle might be. But the results point out potential pitfalls in our attempts to kick-start sleep. 

Zolpidem targets GABA, a chemical messenger that sends “hush” signals. “That means it’s shutting down everything in your brain,” says sleep scientist Robert Stickgold of MIT. It’s a powerful, blunt-force tool that doesn’t need to know why you can’t sleep. Pain, stress, restless legs — these can all lead to insomnia. “Ambien doesn’t care,” Stickgold says. “Ambien is just going to hit you in the back of the head with a sledgehammer.”

Ambien-assisted sleep may be justified for short stretches, Nedergaard says. But long-term use brings considerable side effects. The brain-cleaning disruption may be one. “We need a new sleep aid that gets people to sleep but preserves these oscillations,” she says.

But for people in dire sleep straits, blunt force sleeping pills are better than no sleep at all. “I tell people sleeping meds are terrible things,” Stickgold deadpans. “You should never take them. Unless you can’t sleep well without them.”

Scientists aren’t just trying to help people sleep better. They’re also pushing the limits of what sleeping brains can accomplish. Researchers can instruct a sleeping person to dream about particular objects like trees, sharpen their piano playing skills and maybe even learn a new language. These feats are impressive but they may involve trade-offs, Stickgold warns. If you’re forcing the sleeping brain to do something specific, “then you’re getting less of something else,” he says. “We have to assume that something else is there for a reason.”

Humility is the way forward to understanding – and tinkering with – a system as complex as the sleeping brain.“It is arguably impossible for us to know everything,” Stickgold says.

So maybe we should not expect one simple answer to the question of why we sleep. It could be for growing bones, sharpening memories, cleaning the brain and many more tasks. In the years to come, we will no doubt find new clues about how sleep keeps our bodies and minds healthy. And these scientific breadcrumbs may lead us to yet more mysteries.