542 Table 2 Pre-, post- and difference scores on stress in all conditions (n=20, mean±SEM) Pre Post Difference Control 2.2±0.2 1.6±0.3 −0.6±0.2 Placebo 2.2±0.3 1.8±0.3 −0.4±0.2 Caffeine 2.0±0.3 1.7±0.3 −0.3±0.1 Active placebo 2.0±0.3 1.5±0.2 −0.5±0.2 Psychopharmacology (2011) 215:537–548 repeated measures ANOVA showed a significant three-way interaction F(3, 57) = 4.79, p = .005. Trend analyses showed that there was a significant decrease across blocks in the active placebo condition (linear trend F(1, 19) = 8.34, p = .009), but not in the other conditions. There were no differences in pain over time between the placebo and control condition. Pain was lower in the fourth block in the active placebo condition compared to the caffeine condition (F(1, 19) = 8.17, p = .01; Fig 2b). Fig. 2 Pain report. a Mean pain intensity (± SEM) across conditions. Subjects reported larger reductions in pain after 4 mg/kg caffeine (caffeine, active placebo) compared to after 0 mg caffeine (control, placebo). b Pain reduction displayed as the difference scores (posttest– pretest) for all four blocks of the posttest and pretest (mean ±SEM). A significant interaction between drug, information and block was observed towards the end. This was due to the difference between the active placebo and caffeine conditions. A steady increase in pain relief was observed in the active placebo condition, whereas pain relief was disrupted in the caffeine condition. c Certainty of pain relief correlated with pain reduction in the active placebo condition (r = −.55, p = .012). d Active placebo responding (difference score active placebo − difference score caffeine) (positive scores indicate larger reduction in pain in the active placebo condition) correlated with certainty of pain relief (r = 46, p = .039)