The placebo response: how words and rituals change the patient's brain
Abstract
Objective The placebo effect, or response, has evolved from being thought of as a nuisance in clinical and pharmacological research to a biological phenomenon worthy of scientific investigation in its own right. The study of the placebo effect and of its negative counterpart, the nocebo effect, is basically the study of the psychosocial context around the treatment and the patient, and it plays a crucial role in the therapeutic outcome. Methods In recent years, different types of placebo responses have been analyzed with sophisticated biological tools that have uncovered specific mechanisms at the anatomical, physiological, biochemical and cellular level. Results Most of our knowledge about the neurobiological mechanisms of the placebo response comes from pain and Parkinson's disease, whereby the neuronal circuits involved in placebo responsiveness have been identified. In the first case, opioidergic, dopaminergic and cholecystokinergic networks have been found to be involved. In the second case, dopaminergic activation in the striatum and neuronal changes in basal ganglia have been described. Conclusion This recent research has revealed that these placebo-induced biochemical and cellular changes in a patient's brain are very similar to those induced by drugs. This new way of thinking may have profound implications both for clinical trials and for medical practice.
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The expectation of improvement can be further enhanced through factors such as attention, engagement, feeling well-treated, and participating in therapeutic rituals.
“The expectation of improvement can be further enhanced through factors such as attention, engagement, feeling well-treated, and participating in therapeutic rituals (Benedetti and Amanzio, 2011).”
From Revisiting the SSRI vs. placebo debate in the treatment of social anxiety disorder: the role of expectancy effects, neural responsivity, and monoamine transporters (2025) · cites this paper as Benedetti and Amanzio, 2011
Cites
The somatic marker hypothesis and the possible functions of the prefrontal cortex
Damasio, A. R. (1996) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1996.0125 · Cited by 2,847 · see citing works
Prefrontal cortical function and anxiety: Controlling attention to threat-related stimuli
Bishop, S., Duncan, J., Brett, M., & Lawrence, A. D. (2004) · Nature Neuroscience · doi:10.1038/nn1173 · Cited by 940 · see citing works
Response expectancies in placebo analgesia and their clinical relevance
Pollo, A., Amanzio, M., Arslanian, A., Casadio, C., Maggi, G., & Benedetti, F. (2001) · Pain · doi:10.1016/s0304-3959(01)00296-2 · Cited by 442 · see citing works
Self-citationPetrovic, P., Dietrich, T., Fransson, P., Andersson, J., Carlsson, K., & Ingvar, M. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.023 · Cited by 437 · see citing works
The role of conditioning and verbal expectancy in the placebo response
Voudouris, N. J., Peck, C. L., & Coleman, G. (1990) · Pain · doi:10.1016/0304-3959(90)90057-k · Cited by 369 · see citing works
Volkow, N. D., Wang, G.-J., Ma, Y., Fowler, J. S., Zhu, W., Maynard, L., Telang, F., Vaska, P., Ding, Y.-S., Wong, C., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-36-11461.2003 · Cited by 302 · see citing works
Geers, A. L., Helfer, S. G., Kosbab, K., Weiland, P. E., & Landry, S. J. (2005) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2004.08.011 · Cited by 225 · see citing works
Rief, W., Nestoriuc, Y., von Lilienfeld-Toal, A., Dogan, I., Schreiber, F., Hofmann, S. G., Barsky, A. J., & Avorn, J. (2009) · Drug Safety · doi:10.2165/11316580-000000000-00000 · Cited by 202 · see citing works
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Bishop, F. L., Fenge-Davies, A. L., Kirby, S., & Geraghty, A. W. A. (2015) · Psychology & Health · doi:10.1080/08870446.2014.953529 · Cited by 121 · see citing works
The placebo-nocebo response: controversies and challenges from clinical and research perspective
Jakovljevic, M. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.11.014 · Cited by 63 · see citing works
Wendt, L., Albring, A., Benson, S., Engler, H., Engler, A., Hinney, A., Rief, W., Witzke, O., & Schedlowski, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107665 · Cited by 47 · see citing works
Sanz-Baños, Y., Pastor-Mira, M.-Á., Lledó, A., López-Roig, S., Peñacoba, C., & Sánchez-Meca, J. (2018) · Disability and Rehabilitation · doi:10.1080/09638288.2017.1347722 · Cited by 35 · see citing works
Furmark, T., Wahlstedt, K., & Faria, V. (2025) · Frontiers in Psychology · doi:10.3389/fpsyg.2025.1531725 · Cited by 1 · see citing works
- Authors
- Benedetti, F., & Amanzio, M.
- Affiliations
- University of Turin (IT)
- Corresponding author
- Benedetti, Fabrizio
- Venue
- Patient Education and Counseling
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 84
- Issue
- 3
- Pages
- 413-419
- ISSN
- 0738-3991 (ISSN-L)
- OpenAlex
- W2011087046
- Cited by
- 132
- References
- 8
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 14 · 2018: 15 · 2017: 7 · 2016: 13 · 2015: 8 · 2014: 14 · 2013: 13 · 2012: 6
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Patient Education and Counseling (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Regione Piemonte
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- placebo effect, nocebo effect, placebo response, neurobiological mechanisms, pain, Parkinson's disease, opioid system, dopaminergic system, cholecystokinin, striatum, basal ganglia, clinical trials, medical practice
- MeSH terms
- Mental Disorders, Brain, Communication, Depression, Humans, Physician-Patient Relations, Reward, Placebo Effect, Substance-Related Disorders
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