Normally, Modern Drug Discovery carries only a few articles worth your time, so I was pleasantly surprised when I read a piece on caffeine. As it turns out, it is still not completely understood how caffeine and related compounds work, but most current thinking on its effect on wakefulness and intellectual activity involves its direct chemical impact upon the brain. Contrary to intuitive thinking, caffeine does not act to wake people up. Its real effect is to block the action of the natural relaxation compound adenosine. Under normal conditions, as adensosine builds up during the day and binds to membrane proteins in the brain (primarily the A2A adenosine receptor), loss of concentration and sleepiness occur at some variable threshold point. Caffeine, however, competitvely binds to these adenosine receptors, preventing the sleepiness signal from getting through. Hence, caffeine helps to improve mental performance, but only when other bodily conditions such as fatigue, pain, or sleepiness have diminished it — and then only to unimpeded levels, not as a sudden IQ pill.