Time to recover from daily caffeine intake.

Abstract Caffeine elicits widespread effects in the central nervous system and is the most frequently consumed psychostimulant worldwide. First evidence indicates that, during daily intake, the elimination of caffeine may slow down and the primary metabolite, paraxanthine, may accumulate. The neural impact of such adaptions is virtually unexplored. In this report, we leveraged the data of a laboratory study with N= 20 participants and three within-subject conditions: caffeine (150 mg caffeine x 3/day x 10 days), placebo (150 mg mannitol x 3/day x 10 days), and withdrawal (caffeine x 9 days, afterwards placebo x 1 day). Using liquid chromatography–mass spectrometry coupled with tandem mass spectrometry, we determined the course of salivary caffeine and paraxanthine, measured regularly at day 10. We assessed grey matter (GM) intensity and cerebral blood flow (CBF) in the withdrawal condition as compared to their changes in caffeine in our previous report. The results indicate high remaining levels of paraxanthine and of caffeine carried overnight during daily intake, and the levels of paraxanthine remained higher than in placebo during withdrawal. After 36 h of withdrawal, the previously reported caffeine-induced GM reduction was partially mitigated, while CBF was elevated compared to placebo. Our findings unveil that conventional daily caffeine intake does not provide sufficient time to clear up psychoactive compounds and restore cerebral responses, even after 36 hours of abstinence. They also suggest investigating consequences of a paraxanthine accumulation during daily caffeine intake.