Central and peripheral effects of sustained caffeine use: tolerance is incomplete

Br J Clin Pharmacol. 2002 Oct;54(4):400-6. doi: 10.1046/j.1365-2125.2002.01681.x.


Aims: It is widely held that tolerance develops to the effects of sustained caffeine consumption. This study was designed to investigate the effects of chronic, staggered caffeine ingestion on the responses of an acute caffeine challenge, during -euglycaemia.

Methods: Twelve healthy volunteers were randomized using a double-blind, cross-over design to take either 200 mg caffeine (C-replete) or placebo (C-naïve) twice daily for 1 week. Following baseline measurements being made, the responses to 200 mg caffeine (blood-pressure, middle cerebral artery velocity, mood and cognitive performance) were examined over the subsequent 120 min. Blood glucose was not allowed to fall below 4.0 mmol l-1.

Results: After the caffeine challenge, middle cerebral artery blood velocity decreased in both conditions but was greater in the C-naïve condition (-8.0 [-10.0, -6.1] cm s-1 vs -4.9 [-6.8, -2.9] cm s-1 C-replete, P < 0.02). Systolic blood pressure rise was not significantly different in C-naïve, although this rise was more sustained over time (P < 0.04). Mood was adversely affected by regular caffeine consumption with tense aspect of mood significantly higher at baseline in C-replete 11.6 +/- 0.6 C-naïve vs 16.3 +/- 1.6 C-replete, P < 0.01). Cognitive performance was not affected by previous caffeine exposure.

Conclusions: Overall these results suggest that tolerance is incomplete with respect to both peripheral or central effects of caffeine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects*
  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects*
  • Caffeine / administration & dosage
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Cognition / drug effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Humans
  • Middle Cerebral Artery / drug effects*
  • Psychometrics


  • Central Nervous System Stimulants
  • Caffeine