The placebo effect in reading performance: A cross-over experimental study.

Placebo and its evil twin, nocebo

Clinical neuroscience and neurobiology of placebo and nocebo effects.

Introduction: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. Objective: There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. Methods: Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. Results: There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. Conclusions: The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients’ needs, and on developing standardized disclosure training modules for clinicians.

The nature and magnitude of placebo and nocebo responses to ADHD medications and the extent to which response to active medications and placebo are inter-correlated is unclear. To assess the magnitude of placebo and nocebo responses to ADHD and their association with active treatment response. We searched literature until June 26, 2019, for published/unpublished double-blind, randomised placebo-controlled trials (RCTs) of ADHD medication. Authors were contacted for additional data. We assessed placebo effects on efficacy and nocebo effects on tolerability using random effects meta-analysis. We assessed the association of study design and patient features with placebo/nocebo response. We analysed 128 RCTs (10,578 children/adolescents and 9175 adults) and found significant and heterogenous placebo effects for all efficacy outcomes, with no publication bias. The placebo effect was greatest for clinician compared with other raters. We found nocebo effects on tolerability outcomes. Efficacy outcomes from most raters showed significant positive correlations between the baseline to endpoint placebo effects and the baseline to endpoint drug effects. Placebo and nocebo effects did not differ among drugs. Baseline severity and type of rating scale influenced the findings. Shared non-specific factors influence response to both placebo and active medication. Although ADHD medications are superior to placebo, and placebo treatment in clinical practice is not feasible, clinicians should attempt to incorporate factors associated with placebo effects into clinical care. Future studies should explore how such effects influence response to medication treatment. Upon publication, data will be available in Mendeley Data: PROSPERO (CRD42019130292).

The briefing of patients is part of the daily routine of clinical anaesthesiologists and a central element for justification of medical treatment. It is increasingly apparent that such conversations can significantly affect the success of treatment by eliciting placebo and nocebo effects. Placebo effects are psychosocially caused clinical improvements, mediated by neurobiological mechanisms, which would be omitted in the case of hidden application. Nocebo effects are deteriorations, caused by the same mechanism. Anesthesiologists can make use of the knowledge about placebo and nocebo effects to increase positive impact on the outcome of treatment and to reduce negative effects at the same time. To do so legitimately, physicians have to balance the respect for patients' autonomy, the benevolence, and the non-maleficence for their patients. Patient's autonomy remains the supreme principle of the briefing about treatment and is institutionalized by the informed consent paradigm. Positive and negative expectations are to be handled by patient-oriented communication, but hard paternalistic deceptions and omissions are ethically unjustifiable. We will examine the practical strategies that could be used to deal with the imminent conflict between profound information and optimising placebo and nocebo responses. One key stone of these strategies is the pilot model. It helps to shape briefings as individually required and to promote the wellbeing and autonomy of our patients at the very same time.

Placebo effects constitute a major part of treatment success in medical interventions. The nocebo effect also has a major impact, as it accounts for a significant proportion of the reported side effects for many treatments. Historically, clinical trials have aimed to reduce placebo effects; however, currently, there is interest in optimizing placebo effects to improve existing treatments and in examining ways to minimize nocebo effects to improve clinical outcome. To achieve these aims, a better understanding of the psychological and neurobiological mechanisms of the placebo and nocebo response is required. This review discusses the impact of the placebo and nocebo response in health care. We also examine the mechanisms involved in the placebo and nocebo effects, including the central mechanism of expectations. Finally, we examine ways to enhance placebo effects and reduce the impact of the nocebo response in clinical practice and suggest areas for future research.

Tapasin organizes the peptide-loading complex (PLC) by recruiting peptide-receptive MHC class I (MHC-I) and accessory chaperones to the N-terminal regions of the TAP subunits TAP1 and TAP2. Despite numerous studies...

There is evidence that placebo and nocebo effects are significant for many conditions, but their impact on weight loss has not yet been well described. A systematic review of studies indexed on PubMed, Cochrane, PsycINFO, PsycARTICLES, TripDatabase, and Embase was carried out. Studies (1) with at least two study groups - placebo and a corresponding control group; (2) published in English; and (3) focusing on adults participating in weight loss programs or on placebo/nocebo effects in weight loss were included. Synthesis and meta-analysis of the results of studies with comparable research plans were performed. Some preliminary trends suggesting placebo and nocebo effects in weight loss were found. Placebo effects manifested in trends towards a slightly greater reduction of Body Mass Index (BMI) and body fat ratio in the placebo compared with the control groups. On the other hand, in one study, it was found that the expectancy effects of taking oral weight-loss agents might be disadvantageous (i.e., because they elicit a nocebo effect on weight loss). The findings suggest a possibility that the nocebo effect may occur when an intervention has a medical context. In contrast, the placebo effect can be observed in cases where the intervention is of a different nature. However, considering the low number of studies analyzing the use of placebos in weight loss, new primary research is needed.

Sex has been speculated to be a predictor of the placebo and nocebo effect for many years, but whether this holds true or not has rarely been investigated. We utilized a placebo literature database on various aspects of the genuine placebo/nocebo response. In 2015, we had extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine). These meta-analyses were screened for whether sex/gender differences had been noted to contribute to the placebo/nocebo effect: in only 3 such analyses female sex was associated with a higher placebo effect, indicating poor evidence for a contribution of sex to it in RCTs. This was updated with another set of meta-analyses for the current review, but did not change the overall conclusion. The same holds true for 18 meta-analyses investigating adverse event (nocebo) reporting in RCT in the placebo arm of trials. We also screened our database for papers referring to sex/gender and the placebo effect in experimental studies, and identified 28 papers reporting 29 experiments. Their results can be summarized as follows: (a) Despite higher sensitivity of pain in females, placebo analgesia is easier to elicit in males; (b) It appears that conditioning is effective specifically eliciting nocebo effects; (c) Conditioning works specifically well to elicit placebo and nocebo effects in females and with nausea; (d) Verbal suggestions are not sufficient to induce analgesia in women, but work in men. These results will be discussed with respect to the question why nausea and pain may be prone to be responsive to sex/gender differences, while other symptoms are less. Lastly, we will discuss the apparent discrepancy between RCT with low relevance of sex, and higher relevance of sex in specific experimental settings. We argue that the placebo response is predominantly the result of a conditioning (learning) response in females, while in males it predominantly may be generated via (verbal) manipulating of expectancies. In RCT therefore, the net outcome of the intervention may be the same despite different mechanisms generating the placebo effect between the sexes, while in experimental work when both pathways are separated and explicitly explored, such differences may surface.

Nocebo effects, i.e. reduced treatment effects due to patients' negative expectations, play a role in itch. Recent studies have shown that nocebo effects can be induced experimentally on itch and also be minimized and even turned into the opposite direction, i.e. placebo effects. It is not known whether these effects generalize to itch-associated scratching behaviour. The aim of this study was to determine whether induction and reversal of nocebo effects on itch evoked by electrical and histamine stimuli generalized to scratching. Ninety-seven healthy participants were included in the study. The manipulation was successful, as during the nocebo learning phase, increased scratching responses were found for higher intensity compared with lower intensity itch stimuli. During the testing phase of induction or reversal of the nocebo effects, however, no significant nocebo effects or reversed nocebo effects, were found in scratching. Thus, no straightforward generalization of nocebo effects from itch to scratching was found in this laboratory setting. Further investigation into possible generalization is needed in different settings and in patients with chronic itch.

BackgroundEvidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual’s negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients’ negative expectations and the nocebo effect within dentistry.AimThis review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented.MethodsA PubMed search was performed using keywords related to “nocebo,” “placebo,” “expectations,” and “dentistry.” In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields.ResultsAlthough research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice.ConclusionPreliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry.

Neural mechanisms mediating positive and negative treatment expectations in visceral pain: A functional magnetic resonance imaging study on placebo and nocebo effects in healthy volunteers

The placebo effect and homeopathy

Expectations shape our perception, profoundly influencing how we interpret the world. Positive expectations about sensory stimuli can alleviate distress and reduce pain (e.g., placebo effect), while negative expectations may heighten anxiety and exacerbate pain (e.g., nocebo effect). To investigate the impact of the (an)hedonic aspect of expectations on subjective experiences, we measured neurobehavioral responses to the taste of hot sauce among participants with heterogeneous taste preferences. By identifying participants who "liked" versus those who strongly "disliked" spicy flavors and by providing contextual cues about the spiciness of the sauce to be tasted, we dissociated the effects of positive and negative expectations from sensory stimuli (i.e., visual and gustatory stimuli), which were the same across all participants. Our results indicate that positive expectations lead to modulations in the intensity of subjective experience. These modulations were accompanied by increased activity in brain regions previously linked to information integration and the placebo effect, including the anterior insula, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex, as well as a predefined "pleasure signature." In contrast, negative expectations decreased hedonic experience and increased neural activity in the previously validated "Neurological Pain Signature" network. These findings demonstrate that hedonic aspects of one's expectations asymmetrically shape how the brain processes sensory input and associated behavioral reports of one's subjective experiences of intensity, pleasure, and pain. Our results suggest a dissociable impact of hedonic information: positive expectations facilitate higher-level information integration and reward processing, while negative expectations prime lower-level nociceptive and affective processes. This study demonstrates the powerful role of hedonic expectations in shaping subjective reality and suggests potential avenues for consumer and therapeutic interventions targeting expectation-driven neural processes.

Submit Manuscript | http://medcraveonline.com listening; being present; sharing decisions; and having the intention to heal [3,6,7]. Central to concepts of caring and healing is a sense of connection: to other people, as in a health care or CAM consultation, but also to nature and to spirituality. In addition, people who give or receive healing often mention ‘something else’, an indefinable, metaphysical quality that helps healing happen. Arthur Frank sees healing as ‘the rest’; “the possibility of becoming whole that remains even when nothing remains for curative medicine to do” [8]. The positivist science that underpins modern biomedicine is dismissive of most forms of CAM, and of healing. It insists on the use of placebo-controlled, randomised controlled trials (RCTs) as the only means of ‘proving’ whether a CAM intervention works or not, in spite of the fact that RCTs deliberately factor out all of the contextual factors that may be particularly critical to the efficacy of CAM interventions [9]. Not surprisingly then, in RCTs many CAM interventions do not produce an effect that is deemed satisfactory by biomedical science, and we are therefore told that they ‘do not work’, or that any effect they produce is ‘just a placebo effect’. In this article we explore the interrelationships between placebo effects, the specific effects of interventions, and caring and healing, and suggest that we need to combine the best of each to maximise benefits for our patients. Just a placebo effect The dismissal of CAM interventions as ‘just a placebo’ is interesting. The placebo effect, which has been investigated extensively [10-12] is not completely understood, but clearly involves a multitude of different factors. These include the manner of the interaction between the giver and receiver of health care, the context (both physical and cultural) in which the intervention is used, and the beliefs and expectations of both the therapist and their client [13]. It is also apparent that placebo effects, and their ‘evil twin’ nocebo effects, can be hugely important when it comes to the relief or worsening of symptoms like pain and depression. It has been calculated that 75% or more of the relief of pain and depression achieved with biomedicine can be attributed to the placebo effect (ibid). In other words, most of the value that conventional doctors provide in the treatment of many common conditions is ‘just a placebo effect’. Furthermore, Greville-Harris and colleagues have published evidence to suggest that nocebo effects are even more powerful than placebo effects, and that medical practitioners often unwittingly activate a strong nocebo effect during their well-meant clinical encounters [14]. So, if much biomedicine is ‘just a placebo’, and conventional doctors are often making their patients worse because of their lack of understanding of the nature and power of caring and human interactions, why be troubled by the fact that some CAM interventions may be ‘just a placebo’? Perhaps medical science should celebrate the ability of CAM practitioners to induce a powerful placebo effect, and seek to understand how both CAM and biomedical practitioners can induce placebo. The specific effect within CAM interventions