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Expectation of caffeine induces dopaminergic responses in humans

Recent neuroimaging studies indicate that placebo treatments can induce clinically relevant neurobiological responses in patients with Parkinson's disease, depression and pain. The present study aimed to investigate neurotransmitter function in psychostimulant expectation, with the focus on dopaminergic effects of placebo caffeine in healthy human subjects. Eight habitual coffee drinkers were examined twice with [11C]raclopride positron emission tomography after no treatment and after oral placebo tablets in a counter‐balanced setting. During the placebo condition the subjects were instructed that they had a 50% chance of receiving caffeine, but all received placebo. As compared with no treatment, placebo induced a significant bilateral dopamine release in the thalamus, as reflected by a 15% reduction in thalamic [11C]raclopride binding (P < 0.001). The level of arousal after placebo correlated positively with the tracer binding in the putamen (r = −0.91, P = 0.004). The results indicate that caffeine expectation induces dopaminergic placebo effects, and that these effects are similar to previous findings with oral caffeine. The results therefore suggest that caffeine and placebo caffeine may share some dopaminergic mechanisms of action.