How Does Caffeine Work? The Molecule That Blocks Sleepiness

All day, as the cells of the brain burn fuel, they produce a by-product called adenosine, and it accumulates. Adenosine binds to receptors on neurons and slows them down, damping arousal and building the drowsiness that grows heavier the longer one is awake; it is one of the main components of what sleep scientists call sleep pressure, and sleep clears it. Caffeine has almost the same shape as adenosine. It fits into the same receptors without switching them on, so it sits in the lock and stops the key going in. The adenosine is still there and still building, but the brain cannot feel it, and the sleepiness it would have caused does not arrive.

With the brake lifted, the brain's own stimulants run freer: dopamine, noradrenaline and glutamate all rise, which is why caffeine improves alertness, reaction time and mood, and why it raises heart rate and blood pressure a little and makes some people jittery. It does not make anyone smarter or replace sleep. It postpones the bill.

Caffeine is absorbed within about forty-five minutes and has a half-life in most adults of around five hours, which means that half of a lunchtime coffee is still in the blood at six in the evening and a quarter at eleven. The variation is large: smokers clear it twice as fast, the contraceptive pill and pregnancy slow it, and some people carry a gene variant that makes the liver enzyme responsible sluggish, so that a single espresso keeps them awake all night. The crash comes when the caffeine wears off and the adenosine that built up behind it, unfelt, reaches its receptors all at once. Where it comes from:

• •A mug of filter coffee: about 90 to 140 milligrams, depending on the beans and the brew; espresso about 60 to 80 per shot
• •A cup of tea: about 40 to 50; green tea a little less
• •A can of cola: about 35; an energy drink about 80 to 160
• •A bar of dark chocolate: about 20 to 60
• •Decaffeinated coffee: about 2 to 5, since the process removes most but not all

The brain adapts. Faced with blocked receptors, it grows more of them, and within a week or two of daily use the same dose blocks a smaller share and the effect shrinks. A habitual drinker's morning coffee mostly returns them to the baseline a non-drinker starts from, rather than lifting them above it, which studies of alertness confirm. Stop, and the extra receptors are all suddenly available to adenosine: the result is the headache, fatigue and low mood of caffeine withdrawal, which begins within a day, peaks at one to two days and passes within a week. The headache is partly caffeine's own doing, since it narrows blood vessels in the brain and their rebound widening hurts, which is also why caffeine is added to some painkillers.

The evidence is mostly reassuring. Large studies following hundreds of thousands of people for decades find that moderate coffee drinkers, three or four cups a day, live slightly longer on average than non-drinkers and have lower rates of type 2 diabetes, liver disease and Parkinson's, though coffee contains a thousand other compounds and the caffeine may not be the reason. Regulators put the safe limit for healthy adults at about 400 milligrams a day and for pregnancy at 200, above which the risk of low birth weight rises. Caffeine does raise blood pressure briefly, worsens anxiety and reflux in people prone to them, and taken late in the day cuts deep sleep even in those who fall asleep without trouble, which is the one effect most people underestimate. The recorded deaths are from powders and pills, where a teaspoon can hold a lethal dose; nobody has managed it with coffee.

Caffeine is an insecticide. Coffee, tea, cacao, kola and guarana plants evolved it separately, and it paralyses and kills the insects that eat their leaves and seeds. The plants also put small amounts in their nectar, where it improves the memory of bees for the flower, so that they come back; a plant that drugs its pollinators gets more visits. Humans found the same effect in the same molecule, in Ethiopia, China and the Americas independently, and built three of the world's great trades on it. The first coffee houses opened in Mecca and Cairo around 1500, in London in 1652, and the drink was banned and un-banned several times by rulers who noticed that people who drank it talked politics.

Caffeine keeps you awake by blocking the receptors for adenosine, the chemical that accumulates with wakefulness and makes the brain feel tired, so that sleep pressure builds unfelt and arrives as a crash when the drug wears off after a half-life of about five hours. Daily use grows more receptors and breeds tolerance and withdrawal, moderate intake looks safe or mildly beneficial for most adults, and the molecule exists because it kills insects and rewards bees.