The Brain Hormone That Cleans Your Mind - Or Clogs It...

New research in the journal Cell reveals how the brain cleans itself during sleep, and what medication might constipate that process...

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Why is sleep so important? It’s a deceptively simple question with surprisingly complex answers. But one leading theory is that sleep is the brain’s deep-cleaning cycle, clearing out metabolic waste that accumulates throughout the day. And new research published in Cell just revealed how this process works—along with an alarming connection to a popular sleep medication that might, well… “constipate” the system. Yep, I said that.

We’re about to break it all down. So, sit up, shake off that drowsiness—you won’t want to sleep through this one.

Brain Background: Glymphatics

First, I need to arm you with brain biology background, starting with defining something called the “glymphatic system,” which cleans the brain during sleep.

Throughout the rest of the body, there is a series of vessels called the “lymphatic system” (no “g”). However, your brain – despite being among your most metabolically active organs – lacks a lymphatic system. This is because your brain is packed so full of ~86 billion neurons — not to mention billions more support cells (glia), and a complex network of blood vessels — that there physically isn’t space for another vessel system.

The “glymphatic” system (named for glia + lymphatic) solves this problem. Unlike the lymphatic system, which is a series of tubular vessels, the glymphatic system is a set of channels that expand as blood vessels constrict.

Think about it this way: Imagine you have a blood vessel (artery, below) running through brain tissue, all bathed in cerebrospinal fluid (blue, below). When the blood vessel constricts and shrinks in diameter, it creates space between the vessel and brain tissue, allowing more cerebrospinal fluid to flow through and wash away waste. This is the glymphatic, waste removal system.

And because the brain is less metabolically active during deep sleep, it allows the prime opportunity to constrict blood vessels and turn “on” the glymphatic system. Simply, “non-rapid eye movement” (NREM) deep sleep is peak time for cleaning up the brain.

But how the ffff—enestrated capillaries—does this work?

That was the key question answered by this new research! Hang in with me as there will be some jargon coming up, but we will boil it down…

Norepinephrine: At the Heart of Glymphatic Flow

Through an elegant series of experiments conducted in mice, the researchers were able to show that the neurotransmitter norepinephrine is responsible for glymphatic flow.

Specifically, a group of neurons in the brain stem called the locus coeruleus bathes the brain in norepinephrine pulses while we sleep, particularly in NREM deep sleep. Norepinephrine is a vasoconstrictor, and these pulses therefore generate waves of blood vessel constriction that enhance glymphatic flow and metabolic waste removal.

A Mechanistic Analogy

By way of analogy, think about your gastrointestinal system: Your intestines use rhythmic contractions to move waste out. If that process stops—you get constipated. Now imagine your brain has a similar waste-removal system... but instead of food, it’s clearing out toxic byproducts. If something blocks that process? You get brain constipation. And that’s exactly likely what happens when norepinephrine pulses—and the glymphatic system—aren’t working properly.

Common Sleep Drug, Zolpidem (Ambien), Causes Brain Constipation

The researchers then asked the provocative question: what do certain sleep medications — specifically Zolpidem (Ambien) — do to norepinephrine pulses and glymphatic function?

In brief, they find that the sleep medication impairs the normal oscillations in norepinephrine and decreases glymphatic flow. The implication is that long-term use could contribute to a build-up of metabolic debris in the brain and, possibly, long-term negative consequences like cognitive decline. Indeed, long-term human studies have linked Zolpidem to higher rates of dementia and Alzheimer’s disease.

Fortunately, this does not appear to be the case for other medications that are often used to help with sleep, like the atypical anti-depressant trazodone. In fact, there are suggestions that trazodone might improve sleep architecture and is associated with lower rates of Alzheimer’s disease.

Note: I’m not a sleep scientist. I’m very happy to update this article with more information if/when I receive input from experts. Some people I’ve tagged and hoped to hear from include posts include Andrew Huberman (You know him), Matthew Walker (Professor of Neuroscience at UC Berkeley and Author: Why We Sleep), Mark Czeisler (Brilliant Harvard Medical Student with an interest in sleep science). And I’ve reached out to the first and senior author of this paper. If you have expertise or thoughts, please share them :).

New Frontiers!

An exciting frontier of research involves developing protocols to enhance this system.

For example, I’m currently enjoying using an acoustic neuromodulation device called Elemind (*aside: if you’re interested in trying this device, click HERE, and you can apply discount code: NICKNORWITZ), which has EEG sensors and sends acoustic pulses to interfere with alpha waves and accelerate sleep onset.

Currently, it’s only approved to help you get to sleep faster. But this sort of non-invasive technology may soon be able to alter the microarchitecture of deep sleep, potentially helping to improve glymphatic efficiency!

We could also ask about how different exposures to different types of light at different times during the day might impact sleep microarchitecture and glymphatic flow when we sleep.

And, with advancements in technology, maybe we will soon be able to turn on glymphatics and ‘brain cleaning’ when we’re doing a mindless task, like watching a Marvel Movie, Harry Potter, or Game of Thrones. That’s my nerd dream!

Conclusion

So, what’s the takeaway? Sleep isn’t just about feeling rested—it’s one of your body’s most powerful tools for long-term brain health. Keeping your glymphatic system running smoothly could mean sharper cognition, lower risk of neurodegenerative disease, and better overall performance.

While emerging technologies, from acoustic neuromodulation to light exposure strategies, might one day fine-tune this process, the fundamentals still matter:

• Sleep at consistent times.

• Minimize blue light at night.

• Avoid eating too close to bedtime.

• Keep your sleep environment cool and dark. (Seriously, if you’re sleeping at 70°F or higher… we need to talk.)

Bottom line? Sleep isn’t just important—it’s one of the best brain hacks you have. So, protect it, optimize it, and most importantly—get some.

And don’t miss the clip from the first author, provided exclusively for my YouTube channel and our community.