Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression

Large interindividual differences exist in the presence and extent of placebo responses in both experimental and clinical studies, but little is known about possible predictors of these responses. We employed a behaviorally conditioned immunosuppression paradigm in healthy men to analyze predictors of learned placebo responses. During acquisition, the subjects received either the immunosuppressant cyclosporin A (n = 32) or a placebo (n = 14) (unconditioned stimuli (US)) together with a novel-tasting drink (conditioned stimulus (CS)). During evocation, the subjects were reexposed to the CS alone. In responders (n = 15), the CS alone caused a significant inhibition of interleukin (IL)-2 production by anti-CD3-stimulated peripheral blood T cells, closely mimicking the drug effect. Nonresponders (n = 17) did not show responses different from those of the controls. Multiple-regression analyses showed that baseline IL-2, plasma noradrenaline, and state anxiety predicted nearly 60% of the variance in the conditioned IL-2 response. These data provide first evidence for putative biological and psychological predictors of learned placebo responses.