Caffeine associated stimuli elicit conditioned responses: an experimental model of the placebo effect

Rationale. A neutral stimulus repeatedly paired with administration of a dr ug may elicit a conditioned response. This process, termed pharmacological classical conditioning, may be important in the understanding of placebo ef fects. Objective. The unconditioned response to caffeine is increased physi ological and psychological arousal. The present study investigated whether stimuli associated with the use of caffeine, i.e, the smell and taste of co ffee, elicited a conditioned increase in arousal. It was also investigated whether conditioned arousal modulated the unconditioned arousal induced by caffeine. Methods: Twenty subjects who drank at least two cups of coffee pe r day were exposed to four conditions in a within-subjects design, where th e subjects received coffee or orange juice crossed with placebo or 2 mg/kg caffeine. Dependent variables were skin conductance responses and startle r eflexes to 85 dB noise bursts, skin conductance levels, blood pressure, hea rt rate, and subjective measures of arousal. Results. Both caffeine (caffei nated juice) and caffeine-associated stimuli (decaffeinated coffee) increas ed subjective and physiological arousal. When caffeine and caffeine-associa ted stimuli were presented together (caffeinated coffee), a non-significant tendency towards an additive effect of the conditioned arousal on the unco nditioned arousal to caffeine was seen in some dependent variables. Conclus ions. Presentation of caffeine-associated stimuli to caffeine-users elicite d conditioned responses similar to the unconditioned drug response. Thus, p resentation of caffeine-associated stimuli could be used as an experimental model of placebo effects.