Psychopharmacology (2011) 215:537–548 Table 3 Pre-, post- and difference scores on pain in all conditions (n=20, mean±SEM) Pre Post Difference Control 5.5±0.3 5.6±0.3 0.1±0.2 Placebo 5.3±0.2 5.2±0.2 −0.1±0.2 Caffeine 5.5±0.3 5.1±0.3 −0.4±0.1 Active placebo 5.3±0.3 4.7±0.2 −0.6±0.2 Event-related potentials N2 amplitude The N2 data are presented in Table 4 and Fig. 3. The ANOVA showed an effect of drug that approached significance, F(1, 18) = 4.38, p = .051, with a tendency towards larger reduction in N2 amplitude after 4 mg/kg caffeine compared to 0 mg/kg. There were no other main effects or interactions (Fig. 3a). N2 latency There were no significant main effects or interactions between drug and information in the N2 latency data. P2 amplitude The P2 data are presented in Table 5 and Fig. 4. The ANOVA showed no main effects of drug, information or gender. Neither was there an interaction of drug and information. There was, however, a significant interaction between information and gender F(1, 18) = 4.66, p = .04. Larger reductions of P2 amplitude was observed in males given drug information compared to women given the same information (p = .049). The post hoc test showed a significant reduction in P2 amplitude in the placebo condition compared to the control condition for men (F(1, 18) = 11.28, p = .003), but not for women. There was no difference between the active placebo condition and the caffeine condition for either men or women. P2 latency There were no significant main effects or interactions in the P2 latency data. Order of conditions Order of conditions had no main effect and did not interact with any of the other variables. Table 4 Pre-, post- and differ- ence scores on N2 in all conditions (n =20, mean±SEM) 543 Correlations between the outcome variables Arousal and expectancy It was hypothesised that increased arousal in the active placebo condition should enhance expectancies of treatment efficacy. There was, however, no correlation between increased arousal and certainty of pain relief in the active placebo condition (r(18) = −.06). Arousal and pain Pre- to posttest differences in arousal did not correlate with pain difference scores in any of the conditions. Stress and expectancy In the active placebo condition, subjects that were more certain of pain relief had larger decreases in stress from the pretest to the posttest (r(18)=−.51, p=.02). There was no correlation between certainty of pain relief and stress reduction in the placebo condition. Stress and pain Stress reduction correlated with pain reduction in the active placebo condition (r(18) = .50, p = .03), but not in any of the other conditions. Expectancy and pain In the active placebo condition, subjects that were more certain of pain relief reported larger reductions in pain (r(18) = −.56, p = .01; Fig.2c). Certainty of pain relief also correlated with the active placebo response variable (r(18) = .46, p = .04; Fig 2d): Subjects that were more certain of pain relief responded with larger pain reduction in the active placebo condition compared to the caffeine condition. No correlation was observed in the placebo condition between certainty of pain relief and reduction in pain or between certainty of pain relief and the placebo response variable. Pain and ERPs A positive correlation was observed between the pain intensity difference score and the N2 amplitude difference score in the placebo condition (r(18)=.48, p=.03) and the active placebo condition r(18)=.54, p=.01. Subjects with larger reductions in N2 amplitude reported larger reductions in pain (Fig. 3b and c, respectively). The same was true for P2 amplitude and pain: Subjects with larger reductions in P2 amplitude reported larger reductions in pain in both the placebo condition (r(18)=.49, p=.03) and active placebo condition (r(18) = .60, p = .006; Fig. 4b and c, respectively). There were no correlations between pain and ERPs in the control or caffeine conditions. Pre Post Difference Control −9.5±1.9 −6.8±1.9 −2.7±1.4 Placebo −11.2±1.9 −9..0±1.8 −2.2±1.0 Caffeine −10.9±1.9 −7.4±1.5 −3.5±0.8 Active placebo −10.4±2.0 −6.5±1.4 −3.9±1.0