Placebo responses to cocaine administration in humans: effects of prior administrations and verbal instructions

Subjective and physiological responses of eight male cocaine-using research volunteers were studied after a double-blind saline infusion (placebo) was given when subjects were instructed that a cocaine infusion might be given. Cardiovascular and subjective responses to placebo were similar in pattern and direction, though of lesser magnitude, than after a 40 mg cocaine infusion. These placebo responses were compared to responses after an earlier saline infusion condition in which subjects were instructed prior to the infusion that they would receive saline (instructed placebo). The design was thus meant to test for the effects of instructions on placebo responses to cocaine. Heart rates at baseline (pre-infusion) were significantly higher in the placebo than in the instructed placebo condition. Similar trends were found for elevated baseline placebo responses on two subjective effects measures. A comparison with an initial placebo session prior to the placebo and instructed placebo conditions described above provided evidence for conditioning of placebo responses on diastolic blood pressure and heart rate. The present results suggest that verbal instructions, as well as conditioning in the laboratory, could contribute to the observed placebo responses to cocaine infusions.