Two groups of normal subjects were withdrawn from caffeine for either 24 h (n = 9) or 7 days (n = 12). Following a pre-drug test sequence, subjects were given either 250 mg or 500 mg of anhydrous caffeine or a placebo. Tests were repeated 1, 3 and 5 h later. Tiredness, as measured by a visual analogue scale, was the most sensitive indicator of caffeine withdrawal. Headache was only apparent for subjects off caffeine for 24 h and given placebo, confirming this as a specific withdrawal effect, coming on 24-30 h after stopping caffeine. Alertness was increased by caffeine only in the group abstinent for 24 h. After longer term abstention, caffeine had no effects, confirming that drowsiness and lethargy are transient caffeine withdrawal symptoms.
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