Caffeine withdrawal symptoms and rate of metabolism

Forty normal subjects (mean age 36) had their caffeine intake estimated by keeping a diary (n=40) and also by analysing provided samples of tea and coffee (n=28). A test dose of caffeine (500 mg) was given and a series of salivary samples analysed to estimate pharmacokinetic measures of the rate of caffeine metabolism. They then underwent 48 h of placebo substitution using double-blind procedures. A wide range of physiological, psychological and subjective measures were taken on successive days during withdrawal and resumption of caffeine. On withdrawal, 27 subjects reported tiredness and 18 developed headache. Electroencephalograph, skin conductance and blood pressure changes were apparent. Sleep improved on withdrawal but subjects reported feeling less alert and more tired. The higher the usual caffeine intake, the greater the unpleasant feelings on withdrawal and the more marked the reversal of feelings on resumption. The faster the metabolism of caffeine, the less the drop in anxiety during withdrawal and the less its return on resumption. These correlations were, however, rather weak and sporadic.