Cancer and Metastasis Reviews

, Volume 38, Issue 1–2, pp 315–326 | Cite as

It is not just the drugs that matter: the nocebo effect

  • Marek Z. Wojtukiewicz
  • Barbara Politynska
  • Piotr Skalij
  • Piotr Tokajuk
  • Anna M. Wojtukiewicz
  • Kenneth V. HonnEmail author


The role of psychological mechanisms in the treatment process cannot be underestimated, the well-known placebo effect unquestionably being a factor in treatment. However, there is also a dark side to the impact of mental processes on health/illness as exemplified by the nocebo effect. This phenomenon includes the emergence or exacerbation of negative symptoms associated with the therapy, but arising as a result of the patient’s expectations, rather than being an actual complication of treatment. The exact biological mechanisms of this process are not known, but cholecystokinergic and dopaminergic systems, changes in the HPA axis, and the endogenous secretion of opioids are thought to be involved. The nocebo effect can affect a significant proportion of people undergoing treatment, including cancer patients, leading in some cases to the cessation of potentially effective therapy, because of adverse effects that are not actually part of the biological effect of treatment. In extreme cases, as a result of suggestions and expectations, a paradoxical effect, biologically opposite to the mechanism of the action of the drug, may occur. In addition, the nocebo effect may significantly interfere with the results of clinical trials, being the cause of a significant proportion of complications reported. Knowledge of the phenomenon is thus necessary in order to facilitate its minimalization and thus improve the quality of life of patients and the effectiveness of treatment.


Nocebo Nocebo effect Nocebo mechanism Pharmacotherapy Cancer Psychobiology 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Marek Z. Wojtukiewicz
    • 1
    • 2
  • Barbara Politynska
    • 3
    • 4
  • Piotr Skalij
    • 1
    • 2
  • Piotr Tokajuk
    • 1
    • 2
  • Anna M. Wojtukiewicz
    • 3
  • Kenneth V. Honn
    • 5
    • 6
    • 7
    Email author
  1. 1.Department of OncologyMedical University of BiałystokBialystokPoland
  2. 2.Department of Clinical OncologyComprehensive Cancer CenterBialystokPoland
  3. 3.Department of Philosophy and Human PsychologyMedical University of BiałystokBiałystokPoland
  4. 4.Robinson CollegeCambridge UniversityCambridgeUK
  5. 5.Bioactive Lipids Research ProgramDepartment of Pathology-School of MedicineDetroitUSA
  6. 6.Department of ChemistryWayne State UniversityDetroitUSA
  7. 7.Department of OncologyKarmanos Cancer InstituteDetroitUSA

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