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

Rationale: A neutral stimulus repeatedly paired with administration of a drug may elicit a conditioned response. This process, termed pharmacological classical conditioning, may be important in the understanding of placebo effects. Objective: The unconditioned response to caffeine is increased physiological and psychological arousal. The present study investigated whether stimuli associated with the use of caffeine, i.e. the smell and taste of coffee, 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 per day were exposed to four conditions in a within-subjects design, where the subjects received coffee or orange juice crossed with placebo or 2 mg/kg caffeine. Dependent variables were skin conductance responses and startle reflexes to 85 dB noise bursts, skin conductance levels, blood pressure, heart rate, and subjective measures of arousal. Results: Both caffeine (caffeinated juice) and caffeine-associated stimuli (decaffeinated coffee) increased subjective and physiological arousal. When caffeine and caffeine-associated stimuli were presented together (caffeinated coffee), a non-significant tendency towards an additive effect of the conditioned arousal on the unconditioned arousal to caffeine was seen in some dependent variables. Conclusions: Presentation of caffeine-associated stimuli to caffeine-users elicited conditioned responses similar to the unconditioned drug response. Thus, presentation of caffeine-associated stimuli could be used as an experimental model of placebo effects.