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Abstract

Adverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo effects can be triggered by verbal suggestions, prior negative experiences, observation of others experiencing negative outcomes, and other contextual and environmental factors. As research advances over the years, mechanistic knowledge is accumulating on the neurobiological mechanisms of nocebo effects. This review summarizes studies on different facets of nocebo effects and responses and discusses clinical implications, ethical considerations, and future directions.

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2024-01-23
2024-05-09
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Literature Cited

  1. 1.
    Kennedy WP. 1961. The nocebo reaction. Med. World 95:203–5Widely regarded as the first publication on the nocebo effect.
    [Google Scholar]
  2. 2.
    Barsky AJ, Saintfort R, Rogers MP, Borus JF. 2002. Nonspecific medication side effects and the nocebo phenomenon. JAMA 287:622–27A seminal article on the relevance of the nocebo effect in medicine.
    [Google Scholar]
  3. 3.
    Kissel P, Barrucand D. 1964. Placebos et Effet Placebo en Medecine Paris: Masson
  4. 4.
    Colloca L, Finniss D. 2012. Nocebo effects, patient-clinician communication, and therapeutic outcomes. JAMA 307:567–68
    [Google Scholar]
  5. 5.
    Chavarria V, Vian J, Pereira C, Data-Franco J, Fernandes BS et al. 2017. The placebo and nocebo phenomena: their clinical management and impact on treatment outcomes. Clin. Ther. 39:477–86
    [Google Scholar]
  6. 6.
    Colloca L, Miller FG. 2011. The nocebo effect and its relevance for clinical practice. Psychosomat. Med. 73:598–603
    [Google Scholar]
  7. 7.
    Häuser W, Hansen E, Enck P. 2012. Nocebo phenomena in medicine: their relevance in everyday clinical practice. Dtsch. Arztebl. Int. 109:459–65
    [Google Scholar]
  8. 8.
    Pouillon L, Socha M, Demore B, Thilly N, Abitbol V et al. 2018. The nocebo effect: a clinical challenge in the era of biosimilars. Expert Rev. Clin. Immunol. 14:739–49
    [Google Scholar]
  9. 9.
    Colloca L, Barsky AJ. 2020. Placebo and nocebo effects. N. Engl. J. Med. 382:554–61
    [Google Scholar]
  10. 10.
    Rief W, Avorn J, Barsky AJ. 2006. Medication-attributed adverse effects in placebo groups: implications for assessment of adverse effects. Arch. Intern. Med. 166:155–60
    [Google Scholar]
  11. 11.
    Myers MG, Cairns JA, Singer J. 1987. The consent form as a possible cause of side effects. Clin. Pharmacol. Ther. 42:250–53
    [Google Scholar]
  12. 12.
    Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM et al. 1985. Aspirin, sulfinpyrazone, or both in unstable angina—results of a Canadian multicenter trial. N. Engl. J. Med. 313:1369–75
    [Google Scholar]
  13. 13.
    Papadopoulos D, Mitsikostas DD. 2010. Nocebo effects in multiple sclerosis trials: a meta-analysis. Mult. Scler. 16:816–28
    [Google Scholar]
  14. 14.
    Gklinos P, Papadopoulos D, Mitsikostas DD. 2019. Nocebo in multiple sclerosis trials: a meta-analysis on oral and newer injectable disease-modifying treatments. Mult. Scler. Relat. Disord. 36:101389
    [Google Scholar]
  15. 15.
    Papadopoulos D, Mitsikostas DD. 2012. A meta-analytic approach to estimating nocebo effects in neuropathic pain trials. J. Neurol. 259:436–47
    [Google Scholar]
  16. 16.
    Shafiq F, Mitsikostas DD, Zis P. 2017. Nocebo in motor neuron disease: systematic review and meta-analysis of placebo-controlled clinical trials. Amyotroph. Lateral Scler. Frontotemporal Degener. 18:576–82
    [Google Scholar]
  17. 17.
    Mitsikostas DD, Mantonakis L, Chalarakis N. 2014. Nocebo in clinical trials for depression: a meta-analysis. Psychiatry Res. 215:82–86
    [Google Scholar]
  18. 18.
    Kokoti L, Drellia K, Papadopoulos D, Mitsikostas DD. 2020. Placebo and nocebo phenomena in anti-CGRP monoclonal antibody trials for migraine prevention: a meta-analysis. J. Neurol. 267:1158–70
    [Google Scholar]
  19. 19.
    Mitsikostas DD, Mantonakis LI, Chalarakis NG. 2011. Nocebo is the enemy, not placebo. A meta-analysis of reported side effects after placebo treatment in headaches. Cephalalgia 31:550–61
    [Google Scholar]
  20. 20.
    Mitsikostas DD. 2012. Nocebo in headaches: implications for clinical practice and trial design. Curr. Neurol. Neurosci. Rep. 12:132–37
    [Google Scholar]
  21. 21.
    Mitsikostas DD. 2016. Nocebo in headache. Curr. Opin. Neurol. 29:331–36
    [Google Scholar]
  22. 22.
    Kravvariti E, Kasdagli MI, Diomatari KM, Mouratidou P, Daskalakis K et al. 2023. Meta-analysis of placebo-arm dropouts in osteoporosis randomized-controlled trials and implications for nocebo-associated discontinuation of anti-osteoporotic drugs in clinical practice. Osteoporos. Int. 34:585–98
    [Google Scholar]
  23. 23.
    Amanzio M, Corazzini LL, Vase L, Benedetti F. 2009. A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain 146:261–69
    [Google Scholar]
  24. 24.
    Rief W, Nestoriuc Y, von Lilienfeld-Toal A, Dogan I, Schreiber F et al. 2009. Differences in adverse effect reporting in placebo groups in SSRI and tricyclic antidepressant trials: a systematic review and meta-analysis. Drug Saf. 32:1041–56
    [Google Scholar]
  25. 25.
    Reuter U, Sanchez del Rio M, Carpay JA, Boes CJ, Silberstein SD. 2003. Placebo adverse events in headache trials: headache as an adverse event of placebo. Cephalalgia 23:496–503
    [Google Scholar]
  26. 26.
    Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B et al. 2017. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial---Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet 389:247381Nocebo responses caused discontinuation of atorvastatin and subsequent increases of strokes and heart attacks.
    [Google Scholar]
  27. 27.
    MacKrill K, Gamble GD, Petrie KJ. 2020. The effect of television and print news stories on the nocebo responding following a generic medication switch. Clin. Psychol. Eur. 2:e2623
    [Google Scholar]
  28. 28.
    Crichton F, Petrie KJ. 2015. Accentuate the positive: counteracting psychogenic responses to media health messages in the age of the Internet. J. Psychosom. Res. 79:185–89
    [Google Scholar]
  29. 29.
    Faasse K, Cundy T, Petrie KJ. 2009. Thyroxine: anatomy of a health scare. BMJ 339:b5613
    [Google Scholar]
  30. 30.
    Crichton F, Petrie KJ. 2015. Health complaints and wind turbines: the efficacy of explaining the nocebo response to reduce symptom reporting. Environ. Res. 140:449–55
    [Google Scholar]
  31. 31.
    Crichton F, Chapman S, Cundy T, Petrie KJ. 2014. The link between health complaints and wind turbines: support for the nocebo expectations hypothesis. Front. Public Health 2:220
    [Google Scholar]
  32. 32.
    Kristensen LE, Alten R, Puig L, Philipp S, Kvien TK et al. 2018. Non-pharmacological effects in switching medication: the nocebo effect in switching from originator to biosimilar agent. BioDrugs 32:397–404
    [Google Scholar]
  33. 33.
    Colloca L, Panaccione R, Murphy TK. 2019. The clinical implications of nocebo effects for biosimilar therapy. Front. Pharmacol. 10:1372
    [Google Scholar]
  34. 34.
    Rezk MF, Pieper B. 2017. Treatment outcomes with biosimilars: Be aware of the nocebo effect. Rheumatol. Ther. 4:209–18
    [Google Scholar]
  35. 35.
    Boone NW, Liu L, Romberg-Camps MJ, Duijsens L, Houwen C et al. 2018. The nocebo effect challenges the non-medical infliximab switch in practice. Eur. J. Clin. Pharmacol. 74:655–61
    [Google Scholar]
  36. 36.
    Glintborg B, Sorensen IJ, Loft AG, Lindegaard H, Linauskas A et al. 2017. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann. Rheum. Dis. 76:1426–31
    [Google Scholar]
  37. 37.
    Nikiphorou E, Kautiainen H, Hannonen P, Asikainen J, Kokko A et al. 2015. Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin. Biol. Ther. 15:1677–83
    [Google Scholar]
  38. 38.
    Tweehuysen L, Huiskes VJB, van den Bemt BJF, van den Hoogen FHJ, den Broeder AA. 2017. FRI0200 higher acceptance and persistence rates after biosimilar transitioning in patients with a rheumatic disease after employing an enhanced communication strategy. Ann. Rheum. Dis. 76:557
    [Google Scholar]
  39. 39.
    Odinet JS, Day CE, Cruz JL, Heindel GA. 2018. The biosimilar nocebo effect? A systematic review of double-blinded versus open-label studies. J. Manag. Care Spec. Pharm. 24:952–59
    [Google Scholar]
  40. 40.
    Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F et al. 2016. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open 1:e000142
    [Google Scholar]
  41. 41.
    Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A et al. 2018. American Society of Clinical Oncology statement: biosimilars in oncology. J. Clin. Oncol. 36:1260–65
    [Google Scholar]
  42. 42.
    Eur. Specialist Nurses Organ. 2018. Switch management between similar biological medicines: a communication and information guide for nurses Guidel., Eur. Specialist Nurses Organ. Brussels, Belg: https://www.medicinesforeurope.com/wp-content/uploads/2018/06/biosimilar-nurses-guideline-final.pdf
  43. 43.
    Gasteiger C, den Broeder AA, Stewart S, Gasteiger N, Scholz U et al. 2023. The mode of delivery and content of communication strategies used in mandatory and non-mandatory biosimilar transitions: a systematic review with meta-analysis. Health Psychol. Rev. 17:148–68
    [Google Scholar]
  44. 44.
    Gasteiger C, Groom KM, Lobo M, Scholz U, Dalbeth N, Petrie KJ. 2022. Is three a crowd? The influence of companions on a patient's decision to transition to a biosimilar. Ann. Behav. Med. 56:512–22
    [Google Scholar]
  45. 45.
    Gasteiger C, Jones ASK, Kleinstauber M, Lobo M, Horne R et al. 2020. Effects of message framing on patients' perceptions and willingness to change to a biosimilar in a hypothetical drug switch. Arthritis Care Res. 72:1323–30
    [Google Scholar]
  46. 46.
    Gasteiger C, Lobo M, Dalbeth N, Petrie KJ. 2021. Patients’ beliefs and behaviours are associated with perceptions of safety and concerns in a hypothetical biosimilar switch. Rheumatol. Int. 41:163–71
    [Google Scholar]
  47. 47.
    Wager TD, Atlas LY. 2015. The neuroscience of placebo effects: connecting context, learning and health. Nat. Rev. Neurosci. 16:403–18
    [Google Scholar]
  48. 48.
    Miller FG. 2012. Clarifying the nocebo effect and its ethical implications. Am. J. Bioeth. 12:30–31
    [Google Scholar]
  49. 49.
    Power A, Brown CA, Sivan M, Lenton A, Rainey T et al. 2020. Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility. Pain 161:2720–30
    [Google Scholar]
  50. 50.
    Morton DL, Watson A, El-Deredy W, Jones AK. 2009. Reproducibility of placebo analgesia: effect of dispositional optimism. Pain 146:194–98
    [Google Scholar]
  51. 51.
    Pecina M, Love T, Stohler CS, Goldman D, Zubieta JK. 2015. Effects of the mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures. Neuropsychopharmacology 40:957–65
    [Google Scholar]
  52. 52.
    Pecina M, Azhar H, Love TM, Lu T, Fredrickson BL et al. 2013. Personality trait predictors of placebo analgesia and neurobiological correlates. Neuropsychopharmacology 38:639–46
    [Google Scholar]
  53. 53.
    Wang Y, Chan E, Dorsey SG, Campbell CM, Colloca L. 2022. Who are the placebo responders? A cross-sectional cohort study for psychological determinants. Pain 163:1078–90
    [Google Scholar]
  54. 54.
    Feldhaus MH, Horing B, Sprenger C, Buchel C. 2021. Association of nocebo hyperalgesia and basic somatosensory characteristics in a large cohort. Sci. Rep. 11:762
    [Google Scholar]
  55. 55.
    Colloca L, Akintola T, Haycock NR, Blasini M, Thomas S et al. 2020. Prior therapeutic experiences, not expectation ratings, predict placebo effects: an experimental study in chronic pain and healthy participants. Psychother. Psychosom. 89:371–78
    [Google Scholar]
  56. 56.
    Shafir R, Olson E, Colloca L. 2022. The neglect of sex: a call to action for including sex as a biological variable in placebo and nocebo research. Contemp. Clin. Trials 116:106734
    [Google Scholar]
  57. 57.
    Enck P, Klosterhalfen S. 2019. Does sex/gender play a role in placebo and nocebo effects? Conflicting evidence from clinical trials and experimental studies. Front. Neurosci. 13:160
    [Google Scholar]
  58. 58.
    Vambheim SM, Flaten MA. 2017. A systematic review of sex differences in the placebo and the nocebo effect. J. Pain Res. 10:1831–39
    [Google Scholar]
  59. 59.
    Klosterhalfen S, Kellermann S, Braun S, Kowalski A, Schrauth M et al. 2009. Gender and the nocebo response following conditioning and expectancy. J. Psychosom. Res. 66:323–28
    [Google Scholar]
  60. 60.
    Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH et al. 2017. Neuropathic pain. Nat. Rev. Dis. Primers 3:17002
    [Google Scholar]
  61. 61.
    Colloca L. 2019. The placebo effect in pain therapies. Annu. Rev. Pharmacol. Toxicol. 59:191–211
    [Google Scholar]
  62. 62.
    Colloca L, Sigaudo M, Benedetti F. 2008. The role of learning in nocebo and placebo effects. Pain 136:211–18
    [Google Scholar]
  63. 63.
    Colloca L, Benedetti F. 2006. How prior experience shapes placebo analgesia. Pain 124:126–33
    [Google Scholar]
  64. 64.
    Jensen KB, Kaptchuk TJ, Chen X, Kirsch I, Ingvar M et al. 2015. A neural mechanism for nonconscious activation of conditioned placebo and nocebo responses. Cereb. Cortex 25:3903–10
    [Google Scholar]
  65. 65.
    Jensen KB, Kaptchuk TJ, Kirsch I, Raicek J, Lindstrom KM et al. 2012. Nonconscious activation of placebo and nocebo pain responses. PNAS 109:15959–64
    [Google Scholar]
  66. 66.
    Colloca L, Petrovic P, Wager TD, Ingvar M, Benedetti F. 2010. How the number of learning trials affects placebo and nocebo responses. Pain 151:430–39
    [Google Scholar]
  67. 67.
    Babel P, Bajcar EA, Adamczyk W, Kicman P, Lisinska N et al. 2017. Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia. PLOS ONE 12:e0181856
    [Google Scholar]
  68. 68.
    Colagiuri B, Quinn VF, Colloca L. 2015. Nocebo hyperalgesia, partial reinforcement, and extinction. J. Pain 16:995–1004
    [Google Scholar]
  69. 69.
    Catania AC. 2013. Learning Cornwall-on-Hudson, NY: Sloan
  70. 70.
    Colagiuri B, Park J, Barnes K, Sharpe L, Boakes RA et al. 2021. Pre-exposure, but not overshadowing, inhibits nocebo hyperalgesia. J. Pain 22:864–77
    [Google Scholar]
  71. 71.
    Tu Y, Park J, Ahlfors SP, Khan S, Egorova N et al. 2019. A neural mechanism of direct and observational conditioning for placebo and nocebo responses. Neuroimage 184:954–63
    [Google Scholar]
  72. 72.
    Quinn V, Pearson S, Huynh A, Nicholls K, Barnes K, Faasse K. 2023. The influence of video-based social modelling on the nocebo effect. J. Psychosom. Res. 165:111136
    [Google Scholar]
  73. 73.
    Zhang H, Zhou L, Wei H, Lu X, Hu L. 2017. The sustained influence of prior experience induced by social observation on placebo and nocebo responses. J. Pain Res. 10:2769–80
    [Google Scholar]
  74. 74.
    Vogtle E, Kroner-Herwig B, Barke A. 2016. Nocebo hyperalgesia: contributions of social observation and body-related cognitive styles. J. Pain Res. 9:241–49
    [Google Scholar]
  75. 75.
    Faasse K, Grey A, Jordan R, Garland S, Petrie KJ. 2015. Seeing is believing: impact of social modeling on placebo and nocebo responding. Health Psychol. 34:880–85
    [Google Scholar]
  76. 76.
    Swider K, Babel P. 2013. The effect of the sex of a model on nocebo hyperalgesia induced by social observational learning. Pain 154:1312–17
    [Google Scholar]
  77. 77.
    Vogtle E, Barke A, Kroner-Herwig B. 2013. Nocebo hyperalgesia induced by social observational learning. Pain 154:1427–33
    [Google Scholar]
  78. 78.
    Benedetti F, Durando J, Vighetti S. 2014. Nocebo and placebo modulation of hypobaric hypoxia headache involves the cyclooxygenase-prostaglandins pathway. Pain 155:921–28
    [Google Scholar]
  79. 79.
    Janssens T, Meulders A, Cuyvers B, Colloca L, Vlaeyen JWS. 2019. Placebo and nocebo effects and operant pain-related avoidance learning. Pain Rep. 4:e748
    [Google Scholar]
  80. 80.
    Weng L, Peerdeman KJ, Della Porta D, van Laarhoven AIM, Evers AWM 2022. Can placebo and nocebo effects generalize within pain modalities and across somatosensory sensations?. Pain 163:548–59
    [Google Scholar]
  81. 81.
    Colloca L. 2017. Nocebo effects can make you feel pain. Science 358:44
    [Google Scholar]
  82. 82.
    Faasse K, Martin LR. 2018. The power of labeling in nocebo effects. Int. Rev. Neurobiol. 139:379–406
    [Google Scholar]
  83. 83.
    Kessner S, Wiech K, Forkmann K, Ploner M, Bingel U. 2013. The effect of treatment history on therapeutic outcome: an experimental approach. JAMA Intern. Med. 173:1468–69
    [Google Scholar]
  84. 84.
    Tinnermann A, Geuter S, Sprenger C, Finsterbusch J, Buchel C. 2017. Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia. Science 358:105–8Nocebo effects are associated with an activation of ACC-PAG–spinal cord systems.
    [Google Scholar]
  85. 85.
    Geuter S, Buchel C. 2013. Facilitation of pain in the human spinal cord by nocebo treatment. J. Neurosci. 33:13784–90
    [Google Scholar]
  86. 86.
    Tinnermann A, Sprenger C, Buchel C. 2022. Opioid analgesia alters corticospinal coupling along the descending pain system in healthy participants. eLife 11:e74293
    [Google Scholar]
  87. 87.
    Sprenger C, Eichler I-C, Eichler L, Zollner C, Buchel C. 2018. Altered signaling in the descending pain-modulatory system after short-term infusion of the μ-opioid agonist remifentanil. J. Neurosci. 38:2454–70
    [Google Scholar]
  88. 88.
    Nees F, Becker S, Millenet S, Banaschewski T, Poustka L et al. 2017. Brain substrates of reward processing and the μ-opioid receptor: a pathway into pain?. Pain 158:212–19
    [Google Scholar]
  89. 89.
    Eippert F, Bingel U, Schoell E, Yacubian J, Buchel C. 2008. Blockade of endogenous opioid neurotransmission enhances acquisition of conditioned fear in humans. J. Neurosci. 28:5465–72
    [Google Scholar]
  90. 90.
    Levine JD, Gordon NC, Bornstein JC, Fields HL. 1979. Role of pain in placebo analgesia. PNAS 76:3528–31
    [Google Scholar]
  91. 91.
    Levine JD, Gordon NC, Fields HL. 1978. The mechanism of placebo analgesia. Lancet 2:654–57
    [Google Scholar]
  92. 92.
    Koyama T, McHaffie JG, Laurienti PJ, Coghill RC. 2005. The subjective experience of pain: where expectations become reality. PNAS 102:12950–55
    [Google Scholar]
  93. 93.
    Keltner JR, Furst A, Fan C, Redfern R, Inglis B, Fields HL. 2006. Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. J. Neurosci. 26:4437–43
    [Google Scholar]
  94. 94.
    Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC et al. 2011. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci. Transl. Med. 3:70ra14
    [Google Scholar]
  95. 95.
    Bingel U, Wiech K, Ritter C, Wanigasekera V, Ni Mhuircheartaigh R et al. 2022. Hippocampus mediates nocebo impairment of opioid analgesia through changes in functional connectivity. Eur. J. Neurosci. 56:3967–78
    [Google Scholar]
  96. 96.
    van de Sand MF, Menz MM, Sprenger C, Buchel C. 2018. Nocebo-induced modulation of cerebral itch processing—an fMRI study. Neuroimage 166:209–18
    [Google Scholar]
  97. 97.
    Vlemincx E, Sprenger C, Buchel C. 2021. Expectation and dyspnoea: the neurobiological basis of respiratory nocebo effects. Eur. Respir. J. 58:2003008
    [Google Scholar]
  98. 98.
    Lui F, Colloca L, Duzzi D, Anchisi D, Benedetti F, Porro CA. 2010. Neural bases of conditioned placebo analgesia. Pain 151:816–24
    [Google Scholar]
  99. 99.
    Tu Y, Wilson G, Camprodon J, Dougherty DD, Vangel M et al. 2021. Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability. PNAS 118:e2101273118
    [Google Scholar]
  100. 100.
    Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK. 2008. Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch. Gen. Psychiatry 65:220–31
    [Google Scholar]
  101. 101.
    Benedetti F, Amanzio M, Vighetti S, Asteggiano G. 2006. The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. J. Neurosci. 26:12014–22The nonselective CCK antagonist proglumide blocks nocebo hyperalgesia.
    [Google Scholar]
  102. 102.
    Benedetti F, Amanzio M, Casadio C, Oliaro A, Maggi G. 1997. Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide. Pain 71:135–40
    [Google Scholar]
  103. 103.
    Daniels AM, Sallie R. 1981. Headache, lumbar puncture, and expectation. Lancet 317:1003
    [Google Scholar]
  104. 104.
    Luparello TJ, Leist N, Lourie CH, Sweet P. 1970. The interaction of psychologic stimuli and pharmacologic agents on airway reactivity in asthmatic subjects. Psychosom. Med. 32:509–13
    [Google Scholar]
  105. 105.
    Flaten MA, Simonsen T, Olsen H. 1999. Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom. Med. 61:250–55
    [Google Scholar]
  106. 106.
    Colloca L, Lopiano L, Lanotte M, Benedetti F. 2004. Overt versus covert treatment for pain, anxiety, and Parkinson's disease. Lancet Neurol. 3:679–84
    [Google Scholar]
  107. 107.
    Benedetti F, Colloca L, Lanotte M, Bergamasco B, Torre E, Lopiano L 2004. Autonomic and emotional responses to open and hidden stimulations of the human subthalamic region. Brain Res. Bull. 63:203–11
    [Google Scholar]
  108. 108.
    Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I. 2003. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J. Neurosci. 23:4315–23
    [Google Scholar]
  109. 109.
    Mondaini N, Gontero P, Giubilei G, Lombardi G, Cai T et al. 2007. Finasteride 5 mg and sexual side effects: How many of these are related to a nocebo phenomenon?. J. Sex. Med. 4:1708–12
    [Google Scholar]
  110. 110.
    Varelmann D, Pancaro C, Cappiello EC, Camann WR. 2010. Nocebo-induced hyperalgesia during local anesthetic injection. Anesth. Analg. 110:868–70
    [Google Scholar]
  111. 111.
    Benedetti F, Lanotte M, Lopiano L, Colloca L. 2007. When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience 147:260–71
    [Google Scholar]
  112. 112.
    Benedetti F, Amanzio M, Giovannelli F, Craigs-Brackhahn K, Arduino C, Shaibani A. 2022. Are nocebo effects in adulthood linked to prenatal maternal cortisol levels?. Clin. Neuropsychiatry 19:298–306
    [Google Scholar]
  113. 113.
    Taddio A, Shah V, Gilbert-MacLeod C, Katz J. 2002. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. JAMA 288:857–61
    [Google Scholar]
  114. 114.
    Colloca L. 2017. Tell me the truth and I will not be harmed: informed consents and nocebo effects. Am. J. Bioeth. 17:46–48
    [Google Scholar]
  115. 115.
    Miller FG, Kaptchuk TJ. 2008. The power of context: reconceptualizing the placebo effect. J. R. Soc. Med. 101:222–25
    [Google Scholar]
  116. 116.
    Haas JW, Bender FL, Ballou S, Kelley JM, Wilhelm M et al. 2022. Frequency of adverse events in the placebo arms of COVID-19 vaccine trials: a systematic review and meta-analysis. JAMA Netw. Open 5:e2143955
    [Google Scholar]
  117. 117.
    Fragoulis GE, Bournia VK, Mavrea E, Evangelatos G, Fragiadaki K et al. 2022. COVID-19 vaccine safety and nocebo-prone associated hesitancy in patients with systemic rheumatic diseases: a cross-sectional study. Rheumatol. Int. 42:31–39
    [Google Scholar]
  118. 118.
    Geers AL, Clemens KS, Faasse K, Colagiuri B, Webster R et al. 2022. Psychosocial factors predict COVID-19 vaccine side effects. Psychother. Psychosom. 91:136–38Negative expectations are among the strongest predictors of COVID-19 vaccine side effects.
    [Google Scholar]
  119. 119.
    Geers AL, Clemens KS, Colagiuri B, Jason E, Colloca L et al. 2022. Do side effects to the primary COVID-19 vaccine reduce intentions for a COVID-19 vaccine booster?. Ann. Behav. Med. 56:761–68
    [Google Scholar]
  120. 120.
    Clemens KS, Faasse K, Tan W, Colagiuri B, Colloca L et al. 2023. Social communication pathways to COVID-19 vaccine side-effect expectations and experience. J. Psychosom. Res. 164:111081
    [Google Scholar]
  121. 121.
    Colloca L, Thomas S, Yin M, Haycock NR, Wang Y. 2021. Pain experience and mood disorders during the lockdown of the COVID-19 pandemic in the United States: an opportunistic study. Pain Rep. 6:e958
    [Google Scholar]
  122. 122.
    Calabrese L, Colloca L. 2022. Long COVID-19 and the role of the patient-clinician interaction in symptom management. J. Patient Exp. 9: https://doi.org/10.1177/23743735221143960
    [Crossref] [Google Scholar]
  123. 123.
    Brody H, Colloca L. 2013. Patient autonomy and provider beneficence are compatible. Hastings Cent. Rep. 43:6
    [Google Scholar]
  124. 124.
    Miller FG, Colloca L. 2011. The placebo phenomenon and medical ethics: rethinking the relationship between informed consent and risk-benefit assessment. Theor. Med. Bioeth. 32:229–43
    [Google Scholar]
  125. 125.
    Tversky A, Kahneman D. 1981. The framing of decisions and the psychology of choice. Science 211:453–58
    [Google Scholar]
  126. 126.
    Barnes K, Faasse K, Geers AL, Helfer SG, Sharpe L et al. 2019. Can positive framing reduce nocebo side effects? Current evidence and recommendation for future research. Front. Pharmacol. 10:167
    [Google Scholar]
  127. 127.
    Wells RE, Kaptchuk TJ. 2012. To tell the truth, the whole truth, may do patients harm: the problem of the nocebo effect for informed consent. Am. J. Bioeth. 12:22–29
    [Google Scholar]
  128. 128.
    Clemens KS, Vang M, Colloca L, Sieg M, Vase L et al. 2023. The desire for side-effect information in pain treatment: an experimental analysis of contextual and individual difference factors. PAIN https://doi.org/10.1097/j.pain.0000000000003025
    [Google Scholar]
  129. 129.
    Wendt L, Albring A, Benson S, Engler H, Engler A et al. 2014. Catechol-O-methyltransferase Val158Met polymorphism is associated with somatosensory amplification and nocebo responses. PLOS ONE 9:e107665
    [Google Scholar]
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