Placebo and nocebo effects: an introduction to psychological and biological mechanisms

Placebo and nocebo effects are essential components of medical practice and efficacy research, and can be regarded as a special case of context learning. A fundamental function of the central nervous system is to configure the way in which previous learned context becomes linked to corresponding responses. These responses could be either automatic procedures with little flexibility or highly adaptive procedures modified by associated contexts and consequences. Placebo and nocebo effects may represent a typical example of the combination of the two: conditioning effect, which is an inflexible, instinctual, and automatic response, and cognitive expectancy effect, which is a flexible adaptive response modified by prevailing conscious context. Given the fact that contextual learning originates in the brain, neuroimaging tools have been widely used to study placebo and nocebo effects. In addition, pretest resting state fMRI may be a valuable biomarker to predict placebo responses.