Early study reveals why sleeping pills may not supply the best-quality snooze

Sleeping pills may interfere with the brain's overnight cleaning system, new research in mice suggests.

Like cells everywhere in the body, cells in the brain produce a plethora of waste products that need to be regularly removed to prevent them from accumulating and causing damage. These wastes include toxic molecules associated with neurodegenerative disorders, such as Alzheimer's disease.

Normally, this housekeeping is conducted by the glymphatic system, a network of tunnels that surround the blood vessels in the brain. These tunnels contain a colorless liquid called cerebrospinal fluid, which collects "trash" from cells and then flushes it out of the brain. From there, the trash is processed by the body's larger waste-deposal unit, the lymphatic system.

The glymphatic system operates all the time, but evidence suggests that most of the hard work happens when we sleep. However, experts were unsure exactly what drove this vital process.

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It turns out that, at least in mice, glymphatic clearance is driven by a chemical called norepinephrine, also called noradrenaline. This chemical is released by the brain stem and is best known for its roles in the fight-or-flight system.

Norepinephrine's role in brain cleaning was revealed in a new study published Wednesday (Jan. 8) in the journal Cell.

In the study, brain scans revealed that during deep sleep — a type of non-REM sleep that occurs when we transition from being awake to being asleep — norepinephrine is released in tiny waves about every 50 seconds.

These peaks of norepinephrine cause blood vessels in the brain to constrict, reducing blood flow through them. This creates more space for cerebrospinal fluid to flow through the tunnels of the surrounding glymphatic system and gather up cellular waste products. As norepinephrine levels fall off again, the system resets itself, and then the cycle repeats seconds later.

That's what glymphatic clearance looks like in mice that fall asleep of their own accord. However, the researchers found that sleeping pills may disrupt this whole process.

When the researchers gave mice a common sleeping pill called zolpidem, which is often sold under the brand name Ambien, the drug inhibited the release of norepinephrine by 50% compared with mice that fell asleep without medication. The drug's effects resulted in a more than 30% reduction in fluid transport through the glymphatic system to the brain.

These findings have yet to be confirmed in humans. However, previous studies have shown that our brains show similar fluctuations in the flow of blood and cerebrospinal fluid during deep sleep that may be triggered by norepinephrine. So it's thought that our glymphatic networks work similarly to those of mice.

The research hints that, while taking sleeping pills like zolpidem can help people to fall asleep faster, these drugs may inadvertently reduce a person's quality of sleep and potentially increase their risk of disease.

"Sleep medication in general has been associated with higher all-cause mortality [deaths from any cause] and with cognitive deficits — so there's already some clues that sleep medication is probably not giving you the best sleep," study lead author Natalie Hauglund, a neuroscientist at the University of Oxford in the U.K., told Live Science.

Going forward, the researchers plan to investigate if sleeping pills have any long-term impacts on the brain's overnight cleaning ritual. If they do, scientists may need to develop new sleeping pills that don't derail the glymphatic system, Hauglund said.

"We just want to look at the brain and say, 'Okay, the brain goes to sleep, then everything is fine,'" she said.