How Placebos Change the Patient's Brain
Open accessAbstract
Although placebos have long been considered a nuisance in clinical research, today they represent an active and productive field of research and, because of the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. Indeed, there exists not a single but many placebo effects, with different mechanisms and in different systems, medical conditions, and therapeutic interventions. For example, brain mechanisms of expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena, such as Pavlovian conditioning, cognitive, and social learning. There is also some experimental evidence of different genetic variants in placebo responsiveness. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, the neural networks that are involved have been identified: that is, the opioidergic-cholecystokinergic-dopaminergic modulatory network in pain and part of the basal ganglia circuitry in Parkinson's disease. Important clinical implications emerge from these recent advances in placebo research. First, as the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and rituals of the therapeutic act, may change the chemistry and circuitry of the patient's brain. Second, the mechanisms that are activated by placebos are the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Third, if prefrontal functioning is impaired, placebo responses are reduced or totally lacking, as occurs in dementia of the Alzheimer's type.
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Expectations could modulate reinforcement signals, and if such manipulations affect the reinforcement signal used in calculating prediction errors, it would short-circuit learning by suppressing cue-inconsistent prediction errors.
“If these manipulations affect the reinforcement signal used in calculating prediction errors, it would short-circuit learning by suppressing cue-inconsistent prediction errors.”
From Social information creates self-fulfilling prophecies in judgments of pain, vicarious pain, and cognitive effort (2026) · cites this paper as [38]
The “Expectation of Reward” section says expectations can induce changes through reward mechanisms and that dopamine neurons respond to deviations from predicted outcomes. It does not say that these changes suppress cue-inconsistent prediction errors or short-circuit learning; that proposed consequence is unsupported by the cited paper. (LLM, conf=0.83)
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- Authors
- Benedetti, F., Carlino, E., & Pollo, A.
- Affiliations
- University of Turin (IT)
- Corresponding author
- Benedetti, Fabrizio
- Venue
- Neuropsychopharmacology
- Published
- 2010-06-30
- Volume
- 36
- Issue
- 1
- Pages
- 339-354
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055515
- OpenAlex
- W2019039429
- Cited by
- 446
- References
- 137
- Citations by year
- 2026: 20 · 2025: 33 · 2024: 24 · 2023: 28 · 2022: 22 · 2021: 27 · 2020: 25 · 2019: 38 · 2018: 57 · 2017: 19 · 2016: 25 · 2015: 26 · 2014: 26 · 2013: 30 · 2012: 25
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Compagnia di San Paolo
- Volkswagen Foundation
- Regione Piemonte
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- placebo effect, expectations, anxiety, reward, classical conditioning, social learning, cognitive learning, genetic variants, pain, Parkinson's disease, basal ganglia, drug interactions, prefrontal cortex, Alzheimer's disease, dementia, healing rituals
- MeSH terms
- Affect, Animals, Brain, Brain Chemistry, Cognition, Humans, Mental Processes, Neural Pathways, Pain, Parkinson Disease, Placebos, Placebo Effect
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