How placebo responses are formed: a learning perspective

Colloca, Luana; Miller, Franklin G.

doi:10.1098/rstb.2010.0398

Cited by 270 publications

(273 citation statements)

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“…The placebo effect is defined as the reduction of a symptom, reported by the patient, after the administration of a placebo; it is modulated by the patient's perception of the placebo action 4 . In accordance with recent reports, there are some neurobiological and psychobiological mechanisms which are implicated in placebo effect: expectation and brain reward circuitry, and conditioning 5,6,7 . It has been proposed that positive expectation before treatment relates to positive responses to placebo, through the brain reward circuitry; thus, responsiveness to placebo would be directly related to the effectiveness of the reward system, which is variable between individuals.…”

Section: What Is Placebo Effect? What It Means In Clinical Practice?mentioning

confidence: 49%

Placebo and nocebo effects in the neurological practice

Bittar

Nascimento

2015

Arq. Neuro-Psiquiatr.

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Knowledge of placebo and nocebo effects is essential to identify their influence on the results in clinical practice and clinical trials, and thereby properly interpret their results. It is known that the gold standard of clinical trials research is the double-blind, placebo-controlled, randomized clinical study. The objective of this review is to distinguish specific from non-specific effects, so that the presence of positive effects in the group that received placebo (placebo effect) and the presence of adverse effects in the group receiving placebo (nocebo effect) lead to confounding in interpreting the results. Placebo and nocebo effects have been considered in neurological diseases such as depression, pain, headache, multiple sclerosis, epilepsy. As placebo and nocebo effects are also present in clinical practice, the purpose of this review is to draw attention to their influence on neurological practice, calling attention to the development of measures that can minimize them.Keywords: placebo, nocebo, neuropathic pain, headache, multiple sclerosis, epilepsy, clinical trials.RESUMO O conhecimento dos efeitos placebo e nocebo é essencial para identificar a sua influência sobre os resultados na prática clínica e ensaios clínicos, e, assim, interpretar corretamente seus resultados. Sabe-se que o padrão-ouro dos estudos clínicos de pesquisa é o ensaio clínico randomizado, placebo-controlado, duplo-cego. O objetivo da revisão é distinguir os efeitos específicos e não específicos, de modo que a presença de efeitos positivos no grupo que recebeu placebo (efeito placebo) e a presença de efeitos adversos no grupo que recebeu placebo (efeito nocebo) levam à confusão na interpretação dos resultados. Placebo e nocebo são descritos em doenças neurológicas como a depressão, dor, cefaleia, esclerose múltipla, epilepsia. Como os efeitos placebo e nocebo também se projetam na prática clínica, o objetivo desta revisão é o de destacar sua influência na prática neurológica, chamando a atenção para o desenvolvimento de medidas que possam minimizá-los.Palavras-chave: placebo, nocebo, dor neuropática, cefaleia, esclerose múltipla, epilepsia, ensaios clínicos.The knowledge of the neurobiology and psychology of the placebo and nocebo effects is of great importance, as it can aggregate into basic and clinical research, and in neurological practice 1 . Further, in order to understand better what these effects mean and how do they act, it is possible to evaluate their influence in clinical trials and try to minimize them, by changing the design of such trials in which treatment is tested against a placebo 2 . Additionally, a better understanding of these effects may reflect in changes in health care systems, forcing us to think always on the significance of the placebo and nocebo effects in clinical practice, and to standardize actions to minimize their influence. The progress in this field becomes evident by the growing number of publications involving placebo and nocebo effects, including their prevalence, physiology, impact...

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Section: What Is Placebo Effect? What It Means In Clinical Practice?mentioning

confidence: 49%

Placebo and nocebo effects in the neurological practice

Bittar

Nascimento

2015

Arq. Neuro-Psiquiatr.

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“…Placebo responses (PR) arise from complex and heterogeneous psychoneurobiological learning processes (1), involving contextual conditioning, expectation formation and social learning mechanisms (2). They can be elicited by the perceived treatment context consisting of a variety of interrelated implicit and explicit psychosocial as well as environmental stimulation components within the relational clinician-patient system (3).…”

Section: Introductionmentioning

confidence: 99%

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Kempler

Kossowsky

Schwarz

et al. 2014

The Journal of Pain

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Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat-pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned -stratified for MT and gender -to either an analgesia-expectation or a controlexpectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearmside: low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. PERSPECTIVE: The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children from 6 to 9 years of age. Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. Conflicts of Interest and Source of FundingThe authors declare that there is no conflict of interest. This research was supported by the University of Basel.Running Title: Placebo Analgesia and Magical Thinking in Children Krummenacher et al., 2014 1 Abstract Objective: Higher brain functions such as expectations and beliefs shape the experience of pain. This is most evident in context-induced placebo analgesia (PA), which was recently shown in adults to interact with the trait of magical thinking (MT).In children, PA and the possible relationship between PA and MT has remained unexplored.Methods: Using a lateralized heat-pain paradigm, we investigated the possible modulatory role of PA expectation and MT in response to nociceptive stimuli on the right and left forearm.Participants were 49 right-handed children (6-9 years). In a between-subjects design, half of them were either randomly -stratified for MT and gender -assigned to an analgesia-expectation or a control-expectation condition. Results:Results indicate that, independent of MT, the placebo procedure significantly increased both heat pain threshold (...

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“…The importance of verbal suggestions and expectations for placebo and nocebo effects has meanwhile been demonstrated in numerous experimental studies [22,[27][28][29]. Furthermore, there is now compelling evidence for the validity of classical conditioning theory for explaining placebo effects, because drug-like effects also occur when active treatments administered repetitively are replaced with pharmacological inert interventions such as saline solutions or sugar pills [24,27,30]. Recent studies have additionally demonstrated that social observational learning represents another psychological mechanism for producing placebo responses [31].…”

Section: Introductionmentioning

confidence: 99%

“…The last contribution of the first part provided by Colloca & Miller [27] aims at interpreting, critiquing and conceptualizing the existing experimental and clinical research on placebo (and nocebo) effects though a learning perspective-the process of decoding information and creating expectations. The question whether and how human beings can activate this sort of inbuilt 'endogenous pharmacy' is of utmost interest for all areas of medicine.…”

Section: Overview Of the Theme Issuementioning

confidence: 99%

“…Inspired by the insights stemming from hypnosis research, Kirsch [26] wondered about the underlying psychological function determining the specific response to a suggestion, and he began to focus on the role of expectancy as a mediating psychological variable. The importance of verbal suggestions and expectations for placebo and nocebo effects has meanwhile been demonstrated in numerous experimental studies [22,[27][28][29]. Furthermore, there is now compelling evidence for the validity of classical conditioning theory for explaining placebo effects, because drug-like effects also occur when active treatments administered repetitively are replaced with pharmacological inert interventions such as saline solutions or sugar pills [24,27,30].…”

Section: Introductionmentioning

confidence: 99%

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Introduction to placebo effects in medicine: mechanisms and clinical implications

Meißner

Kohls

Colloca

2011

Phil. Trans. R. Soc. B

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The field of placebo research has made considerable progress in the last years and it has become a major focus of interest. We know now that the placebo effect is a real neurobiological phenomenon and that the brain's 'inner pharmacy' is a critical determinant for the occurrence of psychobiological and behavioural changes relevant to healing processes and well-being. However, harnessing the advantages of placebo effects in healthcare is still a challenge. The first part of the theme issue summarizes and discusses the various kinds of placebo mechanisms across medical fields, thereby not only focusing on two main explanatory models-expectation and conditioning theory-but also taking into account empathy and social learning, emotion and motivation, spirituality and the healing ritual. The second part of the issue focuses on questions related to transferring knowledge from placebo research into clinical practice and discusses implications for the design and interpretation of clinical trials, for the therapeutic settings in daily patient care, and for future translational placebo research.

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How placebo responses are formed: a learning perspective

Cited by 270 publications

References 75 publications

Placebo and nocebo effects in the neurological practice

Placebo and nocebo effects in the neurological practice

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Introduction to placebo effects in medicine: mechanisms and clinical implications

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