Neuro-bio-behavioral mechanisms of placebo and nocebo responses: implications for clinical trials and clinical practice
Open accessAbstract
The placebo effect has often been considered a nuisance in basic and particularly clinical research. This view has gradually changed in recent years due to deeper insight into the neuro-bio-behavioral mechanisms steering both the placebo and nocebo responses, the evil twin of placebo. For the neuroscientist, placebo and nocebo responses have evolved as indispensable tools to understand brain mechanisms that link cognitive and emotional factors with symptom perception as well as peripheral physiologic systems and end organ functioning. For the clinical investigator, better understanding of the mechanisms driving placebo and nocebo responses allow the control of these responses and thereby help to more precisely define the efficacy of a specific pharmacological intervention. Finally, in the clinical context, the systematic exploitation of these mechanisms will help to maximize placebo responses and minimize nocebo responses for the patient's benefit. In this review, we summarize and critically examine the neuro-bio-behavioral mechanisms underlying placebo and nocebo responses that are currently known in terms of different diseases and physiologic systems. We subsequently elaborate on the consequences of this knowledge for pharmacological treatments of patients and the implications for pharmacological research, the training of healthcare professionals, and for the health care system and future research strategies on placebo and nocebo responses.
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Expectancy and anticipation play a central role in the placebo effect, and expectations about treatment success are the most prominent predictor of outcome in psychopharmacological and psychological interventions.
“Previous studies have demonstrated that expectancy and anticipation play a central role in the placebo effect (Rief and Glombiewski, 2017), and it has been proposed that expectations about treatment success are the most prominent predictor of outcome in psychopharmacological and psychological interventions (Schedlowski et al., 2015).”
From Cortisol Response to Stress: The Role of Expectancy and Anticipatory Stress Regulation (2020) · cites this paper as Schedlowski et al., 2015
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BackgroundPlacebo effects in laser-evoked pain potentials.
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“A recent study reported distinct patterns of neural activation induced by positive or negative expectancies, however, that resulted in a correlated placebo and nocebo behavioral response (Freeman et al., 2015).”
BackgroundPlacebo analgesia and the heart
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- Authors
- Schedlowski, M., Enck, P., Rief, W., & Bingel, U.
- Affiliations
- Philipps University of Marburg (DE)
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 67
- Issue
- 3
- Pages
- 697-730
- ISSN
- 0031-6997 (ISSN-L)
- OpenAlex
- W2180491479
- Cited by
- 323
- References
- 431
- Citations by year
- 2026: 19 · 2025: 30 · 2024: 23 · 2023: 17 · 2022: 32 · 2021: 32 · 2020: 44 · 2019: 38 · 2018: 29 · 2017: 24 · 2016: 29 · 2015: 5 · 2014: 1
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Pharmacological Reviews (publishedVersion)
- PubMed (publishedVersion)
- German Medical Science (German Research Foundation) (publishedVersion, cc-by)
- German Medical Science (German Research Foundation) (cc-by)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- placebo effect, nocebo effect, symptom perception, neural mechanisms, cognitive and emotional factors, end-organ function, health professions education, clinical trials, health care system
- MeSH terms
- Animals, Brain, Clinical Trials as Topic, Cognition, Humans, Placebo Effect, Biomedical Research, Nocebo Effect
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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