Skip to main content

Caffeine tolerance and choice in humans

Abstract

Thirty-two healthy subjects with histories of moderate caffeine consumption abstained from dietary caffeine throughout the study. Subjects were stratified into two groups based on several factors including caffeine preference, which was assessed using a caffeine versus placebo choice procedure. Subsequently, subjects received either caffeine (300 mg t.i.d.) or placebo (placebo t.i.d.) for 18 consecutive days, and thereafter were exposed again to a caffeine versus placebo choice procedure. The study documented tolerance development to the subjective effects of caffeine: after chronic dosing, administration of caffeine produced significant subjective effects in the chronic placebo group but not in the chronic caffeine group. The study also provided indirect evidence for tolerance development: during chronic dosing, the chronic caffeine and placebo groups did not differ meaningfully on ratings of mood and subjective effect. When subjects were categorized into caffeine choosers or nonchoosers, caffeine choosers tended to report positive subjective effects of caffeine and negative subjective effects of placebo. Nonchoosers, in contrast, tended to report negative subjective effects of caffeine. Chronic caffeine did not alter the reinforcing effects of caffeine as assessed by caffeine versus placebo choice, possibly because the relatively short duration of caffeine abstinence in the placebo condition was not sufficient to result in maximal withdrawal effects after termination of the relatively high caffeine dose. This study provides the clearest evidence to date of complete tolerance development to a CNS effect of caffeine in humans.

This is a preview of subscription content, access via your institution.

References

  • Ammon HPT, Bieck PR, Mandalaz D, Verspohl EJ (1983) Adaptation of blood pressure to continuous heavy coffee drinking in young volunteers. A double-blind crossover study. Br J Clin Pharmacol 15:701–706

    PubMed  Google Scholar 

  • Barone JJ, Roberts H (1984) Human consumption of caffeine. In: Dews PB (ed) Caffeine: perspectives from recent research. Springer, Berlin Heidelberg New York, pp 59–73

    Google Scholar 

  • Chait LD, Griffiths RR (1983) Effects of caffeine on cigarette smoking and subjective response. Clin Pharmacol Ther 34:612–622

    PubMed  Google Scholar 

  • Colton T, Gosselin RE, Smith RP (1968) The tolerance of coffee drinkers to caffeine. Clin Pharmacol Ther 9:31–39

    PubMed  Google Scholar 

  • Costa PT Jr, McCrae RR (1985) The NEO Personality Inventory Manual, Psychological Assessment Resources, Odessa, FL

    Google Scholar 

  • Eddy NB, Downs AW (1928) Tolerance and cross-tolerance in the human subject to the diuretic effect of caffeine, theobromine and theophylline. J Pharmacol Exp Ther 33:167–174

    Google Scholar 

  • Gilbert RM (1984) Caffeine consumption. In: Spiller GA (ed) The methylxanthine beverages and foods: chemistry, consumption, and health effects. Liss, New York, pp 185–213

    Google Scholar 

  • Goldstein A (1964) Wakefulness caused by caffeine. Naunyn Schmiedeberg's Arch Exp Pathol Pharmakol 248:269–278

    Google Scholar 

  • Goldstein A, Warren R, Kaizer S (1965) Psychotropic effects of caffeine in man. I. Individual differences in sensitivity to caffeine-induced wakefulness. J Pharmacol Exp Ther 149:156–159

    PubMed  Google Scholar 

  • Goldstein A, Kaizer S, Whitby O (1969) Psychotropic effects of caffeine in man. IV. Quantitative and qualitative differences associated with habituation to coffee. Clin Pharmacol Ther 10:489–497

    PubMed  Google Scholar 

  • Griffiths RR, Woodson PP (1988a) Caffeine physical dependence: studies in humans and laboratory animals. Psychopharmacology 94:437–451

    Article  PubMed  Google Scholar 

  • Griffiths RR, Woodson PP (1988b) Caffeine reinforcement in humans. J Pharmacol Exp Ther 246:21–29

    PubMed  Google Scholar 

  • Griffiths RR, Woodson PP (1988c) Reinforcing properties of caffeine: studies in humans and laboratory animals. Pharmacol Biochem Behav 29:419–427

    Article  PubMed  Google Scholar 

  • Griffiths RR, Bigelow GE, Liebson IA (1986a) Human coffee drinking: reinforcing and physical dependence producing effects of caffeine. J Pharmacol Exp Ther 239:416–425

    PubMed  Google Scholar 

  • Griffiths RR, Bigelow GE, Liebson IA, O'Keefe M, O'Leary D, Russ N (1986b) Human coffee drinking: manipulation of concentration and caffeine dose. J Exp Anal Behav 45:133–148

    PubMed  Google Scholar 

  • Griffiths RR, Evans SM, Heishman SJ, Preston KL, Sannerud CA, Wolf B, Woodson PP (1990) Low-dose caffeine physical dependence in humans. J Pharmacol Exp Ther 255:1123–1132

    PubMed  Google Scholar 

  • Haertzen CA (1974) An overview of Addiction Research Center Inventory Scales (ARCI): an appendix and manual of scales. US Government Printing Office, Washington, DC, pp 74–92

    Google Scholar 

  • Hughes JR, Higgins ST, Bickel WK, Hunt WK, Fenwick JW, Gulliver SB, Mireault GC (1991) Caffeine self-administration, withdrawal and adverse effects among coffee drinkers. Arch Gen Psychiatry 48:611–617

    PubMed  Google Scholar 

  • Jacob P III, Wilson M, Benowitz NL (1981) Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatogr 222:61–70

    PubMed  Google Scholar 

  • McNair DM, Lorr M, Droppleman LF (1971) EITS Manual for the Profile of Mood States, Educational and Industrial Testing Service, San Diego, CA

    Google Scholar 

  • Robertson D, Wade D, Workman R, Woosley RL, Oates JA (1981) Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Invest 67:1111–1117

    PubMed  Google Scholar 

  • Spielberger CD, Gorsuch RL, Lushene RE (1970) STAI Manual for the State-Trait Anxiety Inventory (“Self-Evaluation Questionnaire”), Consulting Psychologists Press, Palo Alto, CA

    Google Scholar 

  • Spiller GA (1984) The chemical components of coffee. In: Spiller GA (ed) The methylxanthine beverages and foods: chemistry, consumption, and health effects. Liss, New York, pp 91–147

    Google Scholar 

  • Stern KN, Chait LD, Johanson CE (1989) Reinforcing and subjective effects of caffeine in normal human volunteers. Psychopharmacology 98:81–88

    Article  PubMed  Google Scholar 

  • van Dusseldorp M, Katan MB (1990) Headache caused by caffeine withdrawal among moderate coffee drinkers switched from ordinary to decaffeinated coffee: a 12 week double blind trial. BMJ 300:1558–1559

    PubMed  Google Scholar 

  • Weiss B, Laties VG (1962) Enhancement of human performance by caffeine and the amphetamines. Pharmacol Rev 14:1–36

    PubMed  Google Scholar 

  • Winsor AL, Strongin EI (1933) A study of the development of tolerance for caffeinated beverages. J Exp Psychol 16:725–744

    Google Scholar 

  • Zwyghuizen-Doorenbos A, Roehrs TA, Lipschutz L, Timms V, Roth T (1990) Effects of caffeine on alertness. Psychopharmacology 100:36–39

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Evans, S.M., Griffiths, R.R. Caffeine tolerance and choice in humans. Psychopharmacology 108, 51–59 (1992). https://doi.org/10.1007/BF02245285

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245285

Key words

  • Caffeine
  • Tolerance
  • Reinforcement
  • Physical dependence
  • Chronic exposure
  • Subjective effects
  • Humans