Expectations and associations that heal: Immunomodulatory placebo effects and its neurobiology

The use of placebo may have accompanied healing and medical practices since their origins (Plato; Charmides, 155–156). Recent experimental data indicate that we would be well advised to further consider placebo effects in future therapeutic strategies, with a better knowledge of their potency, psychological basis and underlying neurobiological mechanisms. Current research in the areas of pain, depression and Parkinson’s disease has uncovered some of the potential neurobiological mechanisms of placebo effects. These data indicate that conscious expectation and unconscious behavioral conditioning processes appear to be the major neurobiological mechanisms capable of releasing endogenous neurotransmitters and/or neurohormones that mimic the expected or conditioned pharmacological effects. To date, research on placebo responses affecting immune-related diseases is scarce, but there are consistent indications that skin and mucosal inflammatory diseases, in particular, are strongly modulated by placebo treatments. However, the brain’s capability to modulate peripheral immune reactivity has been impressively demonstrated by paradigms of behavioral conditioning in animal experiments and human studies. Thus, placebo effects can benefit end organ functioning and the overall health of the individual through positive expectations and behavioral conditioning processes.