Caffeine, sleep and wakefulness: implications of new understanding about withdrawal reversal.

The broad aim of this review is to critically examine the implications of new understanding concerning caffeine withdrawal and withdrawal reversal in the context of research concerned with the effects of caffeine on sleep and wakefulness. A comprehensive search was conducted for relevant experimental studies in the PubMED and PsycINFO databases. Studies were assessed with particular reference to methodological adequacy for controlling against confounding due to caffeine withdrawal and withdrawal reversal. This assessment was used to clarify evidence of effects, highlight areas of ambiguity and derive recommendations for future research. It was found that researchers have generally failed to take account of the fact that habitual use of caffeine, even at moderate levels, leads to physical dependence evidenced by physiological, behavioural and subjective withdrawal effects during periods of abstinence. Consequently, there has been near-complete absence of adequate methodological controls against confounding due to reversal of withdrawal effects when caffeine is experimentally administered. The findings of what has been a substantial research effort to elucidate the effects of caffeine on sleep and wakefulness, undertaken over a period spanning decades, are ambiguous. Current shortcomings can be redressed by incorporating suitable controls in new experimental designs.