The nocebo effect can occur when patients are informed of potential side-effects during a consent process.

Nocebo effects have been linked to the activation of brain stress pathways.

Self-hypnosis calming techniques may be an effective way of mitigating nocebo responses.

Negative expectations can cause or increase symptoms and side-effects beyond the physiological effects of a treatment. These responses are referred to as nocebo effects.

The nocebo effect can occur because of (Häuser, et al., 2012):

Being informed of potential side-effects during a consent process. For instance, this can occur upon enrollment in a research study, or when patients are being told about risks of a medical procedure.

Negative past experiences with treatments or environmental exposures. For instance, patients who have developed side-effects after taking previous medications, are more likely to develop side-effects from new medications (Planès, 2016). Patients with asthma who have developed shortness of breath after exposure to an allergen are more likely to develop shortness of breath when they think they have been exposed to this allergen, even in the absence of such exposure (Luparello, 1968).

Negative clinical interactions with a clinician or medical facility that lead to mistrust. An unfavorable treatment environment may also influence patients' expectations and trust, potentially contributing to nocebo responses. (Kothari, 2026).

Interestingly, the type of side-effects that patients develop because of a nocebo effect depends on (1) the possible side-effects from a drug or procedure that they have learned about through a consent process (Amanzio, et al., 2009); (2) whether they have experienced or observed people who have developed certain side-effects following a treatment or exposure (Vögtle, et al., 2013); or (3) when they have heard in the media of particular side-effects as being associated with a particular treatment (Asan, et al., 2024).

The Neurobiology of Nocebo

Nocebo effects have been linked to the activation of brain stress pathways involving the hypothalamic–pituitary–adrenal (HPA) axis, increased cortisol release, and activity in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and periaqueductal gray (PAG) (Raghuraman & Colloca, 2025).

For instance, functional magnetic resonance imaging (fMRI) studies have shown that expectations of increased pain are associated with greater brain activity in regions involved in pain processing and emotional regulation, including the PFC, ACC, and PAG. This can lead patients to have an increased subjective experience of pain.

Furthermore, negative expectations leading to........

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