546 Caffeine A dose of 4 mg/kg caffeine decreased pain compared to 0 mg. Keogh and Witt (2001) tested the effect of 250 mg caffeine versus placebo on pain threshold, pain tolerance and VAS ratings of pain intensity and unpleasantness. Blood pressure was measured in order to determine whether it had any mediating effect. It was found that caffeine increased blood pressure, pain threshold and pain tolerance compared to placebo, while there were no effects on pain intensity and unpleasantness ratings. Pain tolerance was positively corre- lated with systolic blood pressure, indicating a link between caffeine-induced analgesia and blood pressure. This is in line with studies on the relationship of hypertension to pain. Both hypertensives, and normotensives with induced high blood pressure, exhibit decreased pain sensitivity compared to normotensives, or normotensives with low blood pressure, respectively. Unfortunately, no measure of cardiovascular activity was taken in the present study and it is not possible to draw any conclusions regarding the mechanism of caffeine’s analgesic effect. Measures of blood pressure and heart rate should be considered in future studies. Arousal decreased after 0 mg/kg caffeine, whereas arousal after 4 mg/kg caffeine was the same as in the pretest. This is evidence that caffeine increased subjective arousal compared to control levels, which is consistent with previous research (Flaten and Blumenthal 1999; Mikalsen et al. 2001). The effect of drug on N2 amplitude approached significance. There were also reductions in P2 amplitude in both the caffeine and active placebo conditions, but a main effect of drug might have been masked by the comparable reduction in the placebo condition. These data must be interpreted in light of the effect arousal has on LEPs. Beydoun et al. (1993) found that laser stimuli evoked smaller N2 (24% reduction) and P2 (54% reduction) amplitudes when delivered during drowsiness compared to wakefulness, and evoked no response during stage 2 sleep. Consequently, differences in physiological arousal between 4 and 0 mg/kg caffeine could have masked differences in LEPs due to nociceptive processing. There were significant correlations between reductions in N2 and P2 amplitude and reduction in pain in the active placebo condition, showing that pain report was reliable and reflected cortical processing of nociceptive input. There were no correlations between N2 and P2 amplitude reduction in the caffeine condition, indicating that the neural mechanisms underlying pain perception and LEPs are partly different. Drug × information Information that a painkiller had been administered increased the duration of the analgesic effect of caffeine. Psychopharmacology (2011) 215:537–548 The pain relieving effect of caffeine was disrupted in the last block of the posttest when caffeine was administered with no drug information. On the other hand, pain relief increased steadily in the posttest when caffeine was administered with drug information. This resulted in a significantly larger reduction of pain in the last block of the active placebo condition compared to the caffeine condi- tion. The effect of information is consistent with previous research showing that information can modulate the effect of drugs. For instance, Flaten et al. (1999) administered either placebo or the muscle relaxant carisoprodol with relaxant, stimulant information, or no information. Carisoprodol administered with no information or relaxant information decreased tension. A placebo administered with information that it acted as a stimulant increased subjective tension. When carisoprodol was administered with information that it acted as a stimulant, tension increased. Moreover, tension increased even more in the presence of carisoprodol than when the same information was administered together with a placebo. As serum concentrations of carisoprodol increased, so did reported tension. Most likely, information that a stimulant drug had been administered induced expectancies of stimulant effects with a resultant increase in tension. Interoceptive cues from carisoprodol then provided subjects with information that was interpreted in the direction suggested by the verbal information. Hence, expectancies of stimulant effects were updated and boosted by interoceptive cues from the drug. The results of the present study are consistent with such a reciprocal relationship between information and drug. Information that a painkiller had been administered had no effect on pain perception in the presence of 0 mg/kg caffeine. On the other hand, information induced a weak increase in the analgesic effect of 4 mg/kg caffeine. This suggests that, as in the study by Flaten et al. (1999), the drug provided an interoceptive cue that interacted with the verbal information. It was hypothesised that increased arousal after caffeine would provide an interoceptive cue that would enhance expectancies of pain relief and thereby increase the placebo analgesic response in the active placeco condition com- pared to the placebo condition. However, arousal after 4 mg/kg caffeine did not increase compared to the pretest. Thus, the interoceptive cue generated by caffeine was most likely weak. Consequently, no significant enhancement of expectancies was observed in the active placebo condition. Neither was there any correlation between arousal and expectancies in the active placebo condition, or between arousal and pain generally. Possibly, the effect of information in the active placebo condition was related to the analgesic effect of caffeine. In a study by Vase (2005), patients with irritable bowel syndrome were administered an inert placebo or lidocaine for their pain. Expected pain was measured both after 5 and