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Sleep & circadian

Adenosine

DEAdenosin

Adenosine is a small molecule (a purine nucleoside) that builds up in your brain while you are awake, as a byproduct of neurons using energy. It acts on receptors (A1 and A2A) to make you sleepy and dial down arousal. In effect, it is the main molecular signal of 'sleep pressure'. Its levels peak after a long stretch of being awake, then fall during sleep. Caffeine works mainly by blocking adenosine's receptors, without lowering adenosine itself. That is why you get a pronounced sleepiness rebound once the caffeine clears. Beyond sleep, adenosine helps regulate brain blood flow, and it has been implicated in the 'glymphatic' brain-cleaning process that ramps up during deep (slow-wave) sleep.

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Sources

  1. Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW. (1997). Adenosine: A Mediator of the Sleep-Inducing Effects of Prolonged Wakefulness. *Science*doi:10.1126/science.276.5316.1265