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Research ArticleArticle

Caffeine Withdrawal: A Parametric Analysis of Caffeine Dosing Conditions

Suzette M. Evans and Roland R. Griffiths
Journal of Pharmacology and Experimental Therapeutics April 1999, 289 (1) 285-294;
Suzette M. Evans
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Roland R. Griffiths
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Abstract

Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been only moderately well characterized in humans. Four double-blind experiments were conducted in independent groups of healthy participants to assess the conditions under which withdrawal symptoms occur upon cessation of low to moderate doses of caffeine. In experiment 1, there was no evidence that the range or magnitude of caffeine withdrawal symptoms differed when 300 mg of caffeine was consumed as a single dose in the morning versus 100 mg at three time points across the day. In experiment 2, both the range and severity of withdrawal increased as a function of caffeine maintenance dose (100, 300, and 600 mg/day), with even the lowest dose (100 mg) producing significant caffeine withdrawal. Experiment 3 showed that when individuals were maintained on 300 mg caffeine/day and tested with a range of lower doses (200, 100, 50, 25, and 0 mg/day), a substantial reduction in caffeine consumption (≤100 mg/day) was necessary for the manifestation of caffeine withdrawal. Experiment 4 manipulated duration of exposure to caffeine (1, 3, 7, or 14 days of 300 mg/day) and showed that caffeine withdrawal occurred after as little as 3 days of caffeine exposure, with a somewhat increased severity of withdrawal observed after 7 or 14 days of exposure. As a whole, this set of experiments provides the most complete parametric characterization of caffeine withdrawal to date and suggests that caffeine physical dependence can occur under more modest conditions (i.e., fewer doses per day, lower daily dose, shorter duration of exposure) than previously recognized.

Footnotes

  • Send reprint requests to: Roland R. Griffiths, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 550 Nathan Shock Dr., Baltimore, MD 21224.

  • ↵1 This work was supported by the National Institute on Drug Abuse Grant RO1 DA 03890. Portions of these data were presented to the College on Problems of Drug Dependence in Scottsdale, AZ in June, 1995.

  • ↵2 Present address: New York State Psychiatric Institute, 1051 Riverside Dr., Unit 66, New York, NY 10032.

  • Received for publication: July 6, 1998.

  • Abbreviation:
    POMS
    Profile of Mood States Questionnaire
    • Accepted November 25, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 1
1 Apr 1999
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Research ArticleArticle

Caffeine Withdrawal: A Parametric Analysis of Caffeine Dosing Conditions

Suzette M. Evans and Roland R. Griffiths
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 285-294;

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Research ArticleArticle

Caffeine Withdrawal: A Parametric Analysis of Caffeine Dosing Conditions

Suzette M. Evans and Roland R. Griffiths
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 285-294;
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