, Volume 122, Issue 2, pp 158–168 | Cite as

Caffeine attenuates scopolamine-induced memory impairment in humans

  • W. Reidel
  • E. Hogervorst
  • R. Leboux
  • F. Verhey
  • H. van Praag
  • J. Jolles
Original Investigation


Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

Key words

Caffeine Nicotine Scopolamine Cognition Aging Alzheimer's disease 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bartus RT, Dean RL, Pontecorvo MJ, Flicker C (1985) The cholinergic hypothesis: A historical overview, current perspective, and future directions. Ann NY Acad Sci 444:332–358PubMedGoogle Scholar
  2. Benowitz NL, Porchet H, Shiener L, Peyton JI (1988) Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Ther 44:23–38PubMedGoogle Scholar
  3. Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 80:1–46Google Scholar
  4. Briley M (1990) Biochemical strategies in the search for cognition enhancers. Pharmacopsychiatry 2:75–80Google Scholar
  5. Cacabelos R, Nordberg A, Caamano J, Franco-Maside A, Fernandez-Novoa L, Gomez MJ, Alvarez XA, Takeda M, Prous J, Nishimura T, Winblad B (1994) Molecular strategies for the first generations of antidementia drugs (1). Tacrine and related compounds. Drugs of Today 30:295–337Google Scholar
  6. Fagan D, Swift CG, Tiplady B (1988) Effects of caffeine on vigilance and other performance tests in normal subjects. J Psychopharmacol 2:19–25Google Scholar
  7. Gilman AG, Rall TW, Nies AS, Taylor P (1990) Goodman and Gilman's the pharmacological basis of therapeutics. Pergamon Press, New York, pp 150–166Google Scholar
  8. Houx PJ (1991) Cognitive aging and health-related factors. Datawyse, DatawyseGoogle Scholar
  9. Jarvis M (1993) Does caffeine intake enhance absolute levels of cognitive performance? Psychopharmacology 110:45–52PubMedGoogle Scholar
  10. Jones GMM, Sahakian BJ, Warburton DM, Gray JA (1992) Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. Psychopharmacology 108:485–494CrossRefPubMedGoogle Scholar
  11. Klatsky AL, Armstrong MA, Friedman GD (1993) Coffee, tea, and mortality. Ann Epidemiol 3:375–381PubMedGoogle Scholar
  12. Levin ED (1992) Nicotinic systems and cognitive function. Psychopharmacology 108:417–431CrossRefPubMedGoogle Scholar
  13. Lieberman HR, Wurtman RJ, Emde GG, Roberts C, et al. (1987) The effects of low doses of caffeine on human performance and mood. Psychopharmacology 92:308–312CrossRefPubMedGoogle Scholar
  14. Loke WH (1988) Effects of caffeine on mood and memory. Physiol Behav 44:367–372Google Scholar
  15. Molchan SE, Mellow AM, Lawlor BA, Weingartner HJ, Cohen RM, Cohen MR, Sunderland T (1990) TRH attenuates scopolamine-induced memory impairment in humans. Psychopharmacology 100:84–89Google Scholar
  16. Molchan SE, Martinez RA, Hill JL, Weingartner HJ, Thompson K, Vitiello B, Sunderland T (1992) Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model. Brain Res Rev 17:215–226CrossRefPubMedGoogle Scholar
  17. Nehlig A, Daval J-L, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Rev 17:139–170CrossRefGoogle Scholar
  18. Overall JE, Rhoades HM (1987) Adjusting p values for multiple tests of significance. In: Meltzer HY (ed) Psychopharmacology. The third generation of progress. Raven Press, New York, pp 1013–1018Google Scholar
  19. Pollack I, Norman DA (1964) A non-parametric analysis of recognition experiments. Psychon Sci 1:125–126Google Scholar
  20. Preda L, Alberoni M, Bressi S, Cattaneo C et al. (1993) Effects of acute doses of oxiracetam in the scopolamine model of human amnesia. Psychopharmacology 110:421–426CrossRefPubMedGoogle Scholar
  21. Rusted J, Eaton-Williams P (1991) Distinguishing between attentional and amnestic effects in information processing: the separate and combined effects of scopolamine and nicotine on verbal free recall. Psychopharmacology 104:363–366CrossRefPubMedGoogle Scholar
  22. Rusted JM, Warburton DM (1988) The effects of scopolamine on working memory in healthy young volunteers. Psychopharmacology 96:145–152PubMedGoogle Scholar
  23. Stavric B (1992) An update on research with coffee/caffeine (1989–1990). Food Chem Toxicol 30:533–555CrossRefPubMedGoogle Scholar
  24. Sternberg S (1969) Memory scanning: mental processes revealed by reaction time experiments. Am Sci 57:421–457PubMedGoogle Scholar
  25. Surgeon General (1988) Nicotine addiction: the health consequences of smoking. A report of the Surgeon General. US Department of Health and Human Services, RockvilleGoogle Scholar
  26. Swift CG, Tiplady B (1988) The effects of age on the response to caffeine. Psychopharmacology 94:29–31CrossRefPubMedGoogle Scholar
  27. Terry WS, Phifer B (1986) Caffeine and memory performance on the AVLT. J Clin Psychol 42:860–863PubMedGoogle Scholar
  28. Wesnes K, Parrott A (1992) Smoking, nicotine and human performance handbook of human performance. Academic Press, New York, pp 127–167Google Scholar
  29. Wesnes K, Simpson P, Kidd A (1988) An investigation of the range of cognitive impairments induced by scopolamine 0.6 mg s.c. Hum Psychopharmacol 3:27–41CrossRefGoogle Scholar
  30. Wesnes KA, Anand R, Simpson PM, Christmas L (1990) The use of a scopolamine model to study the potential nootropic effects of aniracetam and piracetam in healthy volunteers. J Psychopharmacol 4:219–232Google Scholar
  31. Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New YorkGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • W. Reidel
    • 1
  • E. Hogervorst
    • 1
  • R. Leboux
    • 1
  • F. Verhey
    • 1
  • H. van Praag
    • 1
  • J. Jolles
    • 1
  1. 1.Department of Psychiatry and NeurophysiologyUniversity of LimburgMaastrichtThe Netherlands

Personalised recommendations