title: Does the presence of a pharmacological substance alter the placebo effect?--results of two experimental studies using the placebo-caffeine paradigm.
abstract: OBJECTIVE
  We employed the placebo-caffeine paradigm to test whether the presence or absence of a substance (caffeine) influences the placebo effect.
  
  
  METHODS
  In experiment 1 consisting of four conditions with n = 15 participants each (control, placebo, two double-blind groups, each with placebo only), we maximized the placebo effect through expectation. Effects were assessed with physiological (blood pressure, heart rate), psychomotor (response times), and well-being indicators (self-report). In experiment 2, caffeine was administered in one of the double-blind groups, and another condition was added where caffeine was given openly.
  
  
  RESULTS
  Effect sizes were medium to large for some outcome parameters in experiment 1 and 2, showing partial replicability of the classical placebo effect. Although not formally significant, differences between the double blind placebo conditions of the two experiments (with and without caffeine present) were medium to small. There was a significant difference (p = 0.03) between experiment 1 and experiment 2 in the physiological variables, and a near significant interaction effect between groups and experiments in the physiological variables (p = 0.06).
  
  
  CONCLUSIONS
  The question warrants further scrutiny. The presence of a pharmacological substance might change the magnitude of the placebo response.
authors.affiliation: School of Social Sciences, European Office of the Samueli Institute for Information Biology, University of Northampton, UK. harald.walach@northampton.ac.uk
authors.forename: Harald
authors.initials: H
authors.lastname: Walach
authors.forename: Rainer
authors.initials: R
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D010919:Placebos / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012718:Set, Psychology; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D010919:Placebos; D002110:Caffeine