Reading up on caffeine in preparing to write this post, I found that scientists who have caffeine as their drug of choice (as a subject of study) like pointing out that it is the most widely used psychoactive drug in the world. This surprised me at first. Had you asked me to guess what that drug would be, I would have said “alcohol,” not even really thinking of caffeine as a contender.

But learning this, it’s not hard to see why: after all, I’ve never relied on alcohol to get me through finals week. It’s thanks to caffeine that last semester, I managed to get away with only really starting a major paper 13 hours before it was due, with only a few brief notes prepared in advance, and with normal reasoning telling me I needed to spend 8 of those hours sleeping. And I got an AB+ on the paper. Some of caffeine’s promoters will tell you even more wonderful things about it: One enthusiastic blogger for Wired gave caffeine credit for launching the Enlightenment, and proposed we might get a new Enlightenment the day scientists invent the new caffeine.

So how does this wonder drug work? Caffeine can, in theory, chemically affect several different parts of the body, but as far as we know, the main thing it does at the levels you’ll actually get from drinking a cup of coffee is affect adenosine receptors. Chemically, caffeine is similar enough to adenosine to bind to its receptors, but not similar enough to actually have adenosine’s signaling effect. Thus, caffeine just gets in the way of adenosine doing its work, so less of what adenosine is supposed to do gets done. Adenosine’s role in the nervous system is to say “enough!” to firing neurons, so blocking it increases neuron firing overall. Thus, caffeine is a stimulant.

However, not everything that stimulates neurons causes wakefulness. Your brain has a center dedicated to telling you when to go to sleep; stimulating that will make you sleepy, rather than wake you up. Wiring matters. Turn an excitatory synapse into an inhibitory one, or vice versa, or insert a single inhibitory neuron between two others, and you flip the relationship between those neurons.

As it turns out, there are two main subtypes of adenosine receptors that are affected by caffeine, the A1s and the A2As. The A1s are found throughout the brain, but the A2As are restricted to the basal ganglia, structures deep inside your brain associated mainly with motor control. Somewhat surprisingly, if you know caffeine mainly for its stay-awake effects, this has led to a lot of interest in how caffeine affects motor control. But motor control isn’t wakefulness, so it doesn’t sound like caffeine’s effect on the basal ganglia tells us much about how it works. /On the other hand/, the basal ganglia can send signals to the frontal cortex, which is responsible for higher-order thought, so caffeine could wake up the thinking part of our brains that way.

How exactly does caffeine work, though? Maybe, even though stimulating certain specific parts of the brain puts you to sleep, stimulating it overall wakes you up. There may be more to it than that, though: it seems that during sleep deprivation levels of both adenosine and adenosine receptors, especially the A1s, go up. Similarly, artificially raising adenosine levels makes people sleepy. Maybe adenosine is part of the brain’s mechanism for deciding when it needs to go to sleep.

But wait—how would increasing adenosine activity make people sleepy? We haven’t really answered the key question here. (Compare: “Who made God?”) Maybe there’s some specialized circuitry here. As I explained in my discussion of the retina, circuitry seems like it can do pretty impressive things, even though circuits to do things beyond the most basic sensory processing can be hard to puzzle out. On the other hand, again, it may just be that general inhibition of brain activity, without any special circuit, is how adenosine causes sleepiness.

I’ll wrap up with a last bit of caffeine boosterism. It may be that caffeine is so popular because in some ways it acts like a stimulant, but has unusual properties that make its negative effects less than, say, the amphetamines found in Adderall. Thus, not only is caffeine the sort of drug that would be wonderful to invent in terms of its readily noticeable surface effects, scientists are actually looking at its chemistry for inspiration on how to create new drugs. Excited?