Psychopharmacology (2011) 215:537–548 22 min. Expectancies explained more of the variance in placebo responding 25–40 min after administration of placebo compared to 5–20 min after. This was probably due to an initial decrease in pain during the first 20 min that matched and enhanced subject’s expectancies, i.e. expec- tancies were updated and increased by personal experience of reduced pain. In the present study, the pain relieving effect of caffeine could have functioned as an interoceptive cue that updated and increased subject’s expectancies of pain relief. This could explain why subjects that were more certain of pain relief were more likely to report larger pain relief in the active placebo condition and more likely to show an active placebo response. This is in accordance with the active placebo hypothesis suggested by several authors (Dinnerstein and Halm 1970; Flaten et al. 2004, 1999; Thomson 1982). Laser-evoked potentials were recorded in order to rule out possible effects of response bias and to determine whether reduced pain was related to inhibition of nociceptive process- ing in the brain. There were significant correlations between reductions in LEPs and reductions in pain in the active placebo condition showing that reductions in pain were not due to response bias. Limitations and future directions The analgesic effect of caffeine could have masked the effect of information in the active placebo condition. Consequently, only eight subjects showed larger reduc- tions of pain in the active placebo condition compared to the caffeine condition. In future studies, a drug with no analgesic effects could be used to induce interoceptive cues. For instance, it has been reported that a bolus infusion of the non-selective beta adrenergic agonist isoproterenol induced changes in interoceptive awareness in all participants (Khalsa et al. 2009). Measures of blood pressure and heart rate should be recorded in order to assess correlations between subjective and physiological effects. Verbal information that an over the counter painkiller was administered in a drink did not induce strong expectancies of treatment efficacy. Probably, administration of capsules, or injections, with stronger suggestions of pain relief will induce stronger placebo responses. The inclusion of an additional posttest could also be considered in order to assess the temporal characteristics of drug by information interactions. Conclusions The results of the present study indicate that the effect of a drug can modulate expectancies of treatment effects with a 547 consequent change in the drug response. Hence, the assumption of placebo-controlled clinical trials that the only difference between the drug group and the placebo group consist in the pharmacological actions of the drug might under certain circumstances be mistaken. 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