Nocebo

The nocebo effect refers to adverse health symptoms or worsened outcomes that arise from negative expectations, beliefs, or conditioning in response to an inert or benign treatment, such as a sugar pill, or to information about a treatment. It is not caused by the pharmacological action of the substance itself.

Nocebo is the counterpart to the placebo effect. While placebo effects involve beneficial responses from positive expectations, nocebo effects involve harm or increased symptom burden driven by negative expectations. Both phenomena reflect the influence of psychological and contextual factors on medical outcomes and can occur even when no active treatment is given.

Mechanisms underlying nocebo responses include expectancy, anxiety, prior experiences, and conditioning. Neurobiologically, anticipation and fear activate brain networks that modulate symptom perception and trigger stress responses, including autonomic arousal and the release of stress hormones. Psychological and social factors shape how information is interpreted, which symptoms are noticed, and how strongly they are reported.

Determinants of nocebo responses include how risks and side effects are communicated, framing of information, cultural background, personality traits such as anxiety or neuroticism, and past treatment experiences. Clinically, nocebo effects can inflate reported adverse events, reduce adherence to therapies, and complicate trial results.

History and terminology: the term nocebo was coined by Walter Kennedy in 1961 to describe harmful effects produced by negative expectations, contrasting with placebo. The concept has since become central to understanding how patient expectations influence treatment outcomes.