What Caffeine Does to Your Brain: A Cellular Chronicle of the Most Common Psychoactive Drug

Staring into the abyss

Some mornings my mind gets trapped in a fog of pain. I can’t concentrate, my body aches, I’m nauseated, I’m irritable, and I can feel my pulse pound-pound-pounding in my head. I haven’t done anything extreme to warrant this internal pestilence. Rather, not doing something is the source of my problem. I’m in withdrawal—I’m craving my drug. I haven’t had my coffee (and with it, my morning dose of caffeine).

Everybody knows caffeine. They know the jolt of energy it might give you. They know it lurks in coffee and energy drinks and soda. They know having too much in the evening will make you restless all night. They know how it infiltrates the totally mundane aspects of our lives. But it has also crept into less likely places. Caffeine is found in gum, waffles, jelly beans, syrup, water, ice cream, lollipops, chocolate candy, and more. By the Food and Drug Administration‘s estimates, 80 percent of adults in the US consume caffeine every day. It’s so silent, prevalent, and covert that we often forget it’s a drug—the world’s most popular drug.

In 1994, researchers at Johns Hopkins confirmed what has always been anecdotally regarded as true: caffeine is addictive. As the New York Times then reported, “Caffeine addicts may try to give up their coffee, tea or cola habit but usually cannot, even when it threatens their health. Like emphysema patients who continue smoking cigarettes, they continue to use caffeine against their doctors’ orders.” In May 2013, the American Psychiatric Association labeled caffeine withdrawal as a mental disorder in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), further legitimizing the power of caffeine.

Caffeine and Adenosine

They look identical, right? It’s that double ring that does the trick.

Caffeine has such an incredible effect on our bodies because of two unique properties:

  • It’s both water and fat soluble, which gives an an all-access pass to our bodies and lets it cross the blood-brain barrier;
  • And it’s similar enough in molecular shape to adenosine that it can block adenosine receptors in the brain.

Adenosine plays many roles related to energy in the human body. To speak very generally, every time a neuron fires, adenosine is produced. As this adenosine builds up, it eventually binds with adenosine receptors which signal the brain to relax. This is why we get drowsy. Our body has a natural way of shutting down. Caffeine plays the perfect adenosine impersonator. It binds to the adenosine receptors, but it fails to signal the brain to slow things down. With caffeine on the receptors, there’s no place for the adenosine to go, so the body fails to slow down.

Blocking the receptors does have some ancillary effects: it allows the brains stimulants like dopamine and glutamate to work more efficiently; and the build up of adenosine causes the pituitary gland to produce more adrenaline. But the main effect is to prevent the brain from slowing down. Stephen R. Braun, author of Buzz: the Science and Lore of Caffeine and Alcohol, compares ingesting caffeine to “putting a block of wood under one of the brain’s primary brake pedals.” The caffeine doesn’t stimulate the brain itself, but it does ruin the brakes.

Because of this, coffee can’t get you more wired than your body could naturally be. It doesn’t over-stimulate you. It just lets you work at your peak while keeping tiredness at bay. It’s best to think of caffeine as something that will make you faster, not smarter or more powerful.

When people consume caffeine on a regular schedule, the body starts to catch on and the brain adapts its biochemistry. It knows it should be tired, but for some reason the adenosine receptors don’t seem to be working, so it develops more adenosine receptors. This is why people grow a tolerance for caffeine. X amount of caffeine used to be able to block Y receptors. But now there are twice as many receptors, you’ll need more caffeine for it to have any effect.

And if you suddenly stop taking caffeine after your biochemistry has altered itself, you pull the rug out from underneath the whole system. With no caffeine, none of the receptors are being unnaturally blocked so the brain receives an influx of signals telling it to slow down. And headaches, extreme drowsiness, and nausea come cascading down on your body as a result.

Fortunately caffeine withdrawal can be treated in two ways: consuming more caffeine (I suppose that’s not a real treatment), or not consuming coffee for a little over a week. Caffeine does have benefits and withdrawal isn’t particularly pleasant, so as long as you’re consuming a healthy amount of caffeine (under 400 mg/day) feel free to keep at it. But if you do want to kick the caffeine habit, it only takes 10 days or so for your body to reestablish a baseline for life without the neurotransmitter impostors.


Smithsonian Mag

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