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I'll admit this curiosity is based on a personal experience I'll document here, but I do believe it's an interesting and useful academic question to study and explore.

For a while, I've noticed that caffeine doesn't give me the same buzz it used to. Fair enough, that's just tolerance, and according to the oh-so-accurate internet (many sources, none of them journal articles, so I'll leave them out unless you really want them), it should take about a week or two without caffeine to revert to pre-tolerance caffeine sensitivity.

So I went a week without caffeine, and then had a single energy drink, and for about 30 minutes, I felt buzzed and awake, and now about an hour later, I feel tired and sluggish again. Considering 30 minutes is nowhere near the biological half-life of caffeine, it can't be that the caffeine was already broken down, it must be something else: acute tolerance, some mechanism by which tolerance forms after a single exposure.

In caffeine, what is the mechanism of this acute tolerance?

Sources:

  1. Pharmacology of Caffeine - Caffeine for the Sustainment of Mental Task Performance

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