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PloS One 2015The influence of positive or negative expectations on clinical outcomes such as pain relief or motor performance in patients and healthy participants has been...
The influence of positive or negative expectations on clinical outcomes such as pain relief or motor performance in patients and healthy participants has been extensively investigated for years. Such research promises potential benefit for patient treatment by deliberately using expectations as means to stimulate endogenous regulation processes. Especially regarding recent interest and controversies revolving around cognitive enhancement, the question remains whether mere expectancies might also yield enhancing or impairing effects in the cognitive domain, i.e., can we improve or impair cognitive performance simply by creating a strong expectancy in participants about their performance? Moreover, previous literature suggests that especially subjective perception is highly susceptible to expectancy effects, whereas objective measures can be affected in certain domains, but not in others. Does such a dissociation of objective measures and subjective perception also apply to cognitive placebo and nocebo effects? In this study, we sought to investigate whether placebo and nocebo effects can be evoked in cognitive tasks, and whether these effects influence objective and subjective measures alike. To this end, we instructed participants about alleged effects of different tone frequencies (high, intermediate, low) on brain activity and cognitive functions. We paired each tone with specific success rates in a Flanker task paradigm as a preliminary conditioning procedure, adapted from research on placebo hypoalgesia. In a subsequent test phase, we measured reaction times and success rates in different expectancy conditions (placebo, nocebo, and control) and then asked participants how the different tone frequencies affected their performance. Interestingly, we found no effects of expectation on objective measures, but a strong effect on subjective perception, i.e., although actual performance was not affected by expectancy, participants strongly believed that the placebo tone frequency improved their performance.
Topics: Adult; Brain; Central Nervous System Stimulants; Cognition; Female; Humans; Male; Nocebo Effect; Nootropic Agents; Perception; Placebo Effect; Psychomotor Performance; Young Adult
PubMed: 26148009
DOI: 10.1371/journal.pone.0130492 -
Scientific Reports Nov 2022The placebo effect is a powerful psychobiological phenomenon whereby a positive outcome follows the administration of an inert treatment thought to be effective. Growing... (Randomized Controlled Trial)
Randomized Controlled Trial
The placebo effect is a powerful psychobiological phenomenon whereby a positive outcome follows the administration of an inert treatment thought to be effective. Growing evidence shows that the placebo effect extends beyond the healing context, affecting also motor performance. Here we explored the placebo effect on the control of goal-directed movement, a fundamental function in many daily activities. Twenty-four healthy volunteers performed upper-limb movements toward a target at different indexes of difficulty in two conditions: in the placebo condition, an electrical device (inert) was applied to the right forearm together with verbal information about its positive effects in improving movement precision; in the control condition, the same device was applied along with verbal information about its neutral effects on performance. Interestingly, we found shorter movement time in the placebo compared to the control condition. Moreover, subjective perception of fatigability was reduced in the placebo compared to the control condition. These findings indicate that the placebo effect can improve the execution of goal-directed movements, thus adding new evidence to the placebo effect in the motor domain. This study could inspire future applications to improve upper-limb movements or in clinical settings for patients with motor deficits.
Topics: Humans; Forearm; Goals; Movement; Placebo Effect; Psychomotor Performance; Upper Extremity
PubMed: 36380087
DOI: 10.1038/s41598-022-23489-y -
Scientific Reports Jun 2023Nausea often occurs in stressful situations, such as chemotherapy or surgery. Clinically relevant placebo effects in nausea have been demonstrated, but it remains... (Randomized Controlled Trial)
Randomized Controlled Trial
Nausea often occurs in stressful situations, such as chemotherapy or surgery. Clinically relevant placebo effects in nausea have been demonstrated, but it remains unclear whether stress has an impact on these effects. The aim of this experimental study was to investigate the interplay between acute stress and placebo effects in nausea. 80 healthy female volunteers susceptible to motion sickness were randomly assigned to either the Maastricht Acute Stress Test or a non-stress control condition, and to either placebo treatment or no treatment. Nausea was induced by a virtual vection drum and behavioral, psychophysiological as well as humoral parameters were repeatedly assessed. Manipulation checks confirmed increased cortisol levels and negative emotions in the stressed groups. In the non-stressed groups, the placebo intervention improved nausea, symptoms of motion sickness, and gastric myoelectrical activity (normo-to-tachy (NTT) ratio). In the stressed groups, the beneficial effects of the placebo intervention on nausea and motion sickness remained unchanged, whereas no improvement of the gastric NTT ratio was observed. Results suggest that placebo effects on symptoms of nausea and motion sickness are resistant to experimentally-induced stress. Stress most likely interfered with the validity of the gastric NTT ratio to measure nausea and thus the gastric placebo effect.
Topics: Female; Humans; Motion Sickness; Nausea; Placebo Effect; Stomach
PubMed: 37336972
DOI: 10.1038/s41598-023-36296-w -
Clinical Pharmacology and Therapeutics Dec 2019In randomized clinical trials (RCTs), it is assumed that nonspecific effects beyond action of pharmacological agents are roughly equivalent in drug and placebo treatment...
In randomized clinical trials (RCTs), it is assumed that nonspecific effects beyond action of pharmacological agents are roughly equivalent in drug and placebo treatment groups. Hence, since the inception of RCTs, drug efficacy is determined by comparing outcomes in active to those in placebo control arms. However, quantitation of efficacy is based on an unproven assumption, that drug and placebo responses are always additive. Response to treatment in RCTs can be differentially influenced by the perturbing effects of patient expectations, side effects, and pharmacogenomic interactions in both drug and placebo arms. Ability to control for these effects requires understanding of when and where they arise, how to mitigate, analyze, and even leverage their impact. Here, we examine three factors that influence additivity: expectation, side effects, and pharmacogenomics. Furthermore, to provide novel insights into nonadditivity and solutions for managing it, we introduce systems pharmacogenomics, a network approach to integrating and analyzing the effects of the numerous interacting perturbations to which a patient is exposed in RCTs.
Topics: Drugs, Investigational; Humans; Pharmacogenetics; Placebo Effect; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 31502253
DOI: 10.1002/cpt.1626 -
NeuroImage May 2021Neural networks involved in placebo analgesia and nocebo hyperalgesia processes have been widely investigated with neuroimaging methods. However, few studies have... (Meta-Analysis)
Meta-Analysis
Neural networks involved in placebo analgesia and nocebo hyperalgesia processes have been widely investigated with neuroimaging methods. However, few studies have directly compared these two processes and it remains unclear whether common or distinct neural circuits are involved. To address this issue, we implemented a coordinate-based meta-analysis and compared neural representations of placebo analgesia (30 studies; 205 foci; 677 subjects) and nocebo hyperalgesia (22 studies; 301 foci; 401 subjects). Contrast analyses confirmed placebo-specific concordance in the right ventral striatum, and nocebo-specific concordance in the dorsal anterior cingulate cortex (dACC), left posterior insula and left parietal operculum during combined pain anticipation and administration stages. Importantly, no overlapping regions were found for these two processes in conjunction analyses, even when the threshold was low. Meta-analytic connectivity modeling (MACM) and resting-state functional connectivity (RSFC) analyses on key regions further confirmed the distinct brain networks underlying placebo analgesia and nocebo hyperalgesia. Together, these findings indicate that the placebo analgesia and nocebo hyperalgesia processes involve distinct neural circuits, which supports the view that the two phenomena may operate via different neuropsychological processes.
Topics: Analgesia; Brain; Brain Mapping; Humans; Hyperalgesia; Magnetic Resonance Imaging; Nerve Net; Nocebo Effect; Pain; Placebo Effect; Positron-Emission Tomography
PubMed: 33549749
DOI: 10.1016/j.neuroimage.2021.117833 -
International Review of Neurobiology 2018Pain, a noxious psychosensory experience, motivates escape behavior to assure protection and survival. Psychological factors alter the experience and trajectory of pain,... (Review)
Review
Pain, a noxious psychosensory experience, motivates escape behavior to assure protection and survival. Psychological factors alter the experience and trajectory of pain, as well as behavior and treatment response. In the context of pain, the placebo effect (expectation for pain relief) releases endogenous opioids and facilitates analgesia from exogenously administered opioids. Nocebo hyperalgesia (expectation for persistent or worsening pain) opposes endogenous opioid analgesia and patient engagement in prescription opioid tapering. Reductions in nocebo hyperalgesia and pain catastrophizing may enhance descending modulation of pain, mediate adaptive structural brain changes and promote patient engagement in opioid tapering. Interventions that minimize nocebo and optimize placebo may adaptively shape the central nervous system toward pain relief and potentially opioid reduction. Here we provide a critical description of catastrophizing and its impact on pain, placebo and nocebo effects. We also consider the importance of minimizing nocebo and optimizing placebo effects during prescription opioid tapering, and offer a clinical toolkit of resources to accomplish these goals clinically.
Topics: Analgesics, Opioid; Catastrophization; Humans; Hyperalgesia; Nocebo Effect; Pain; Pain Management; Placebo Effect
PubMed: 30146045
DOI: 10.1016/bs.irn.2018.07.022 -
Journal of the Peripheral Nervous... Sep 2020The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on...
The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post-hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo-controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non-deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.
Topics: Humans; Immunologic Factors; Outcome Assessment, Health Care; Placebo Effect; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Randomized Controlled Trials as Topic; Research Design
PubMed: 32627277
DOI: 10.1111/jns.12402 -
International Review of Neurobiology 2018Placebo analgesia is a robust experimental and clinical phenomenon. While our understanding of the mechanisms of placebo analgesia has developed rapidly, some central...
Placebo analgesia is a robust experimental and clinical phenomenon. While our understanding of the mechanisms of placebo analgesia has developed rapidly, some central questions remain unanswered. Among the important questions is how placebo analgesia interacts with active analgesic effects. It is an assumption underlying double-blind randomized placebo-controlled trials (RCTs) that the true effect of a treatment can be determined by examining the effect of the active treatment arm and subtracting the response in the placebo group ("the assumption of additivity"). However, despite the importance of this assumption for the interpretation of RCTs, it has rarely been formally examined. This article reviews the assumption of additivity in placebo analgesia by examining studies employing factorial designs manipulating both the receipt of an active analgesic and instructions about the treatment being delivered. In reviewing the literature, we identified seven studies that allowed a test of additivity. Of these, four found evidence against additivity, while the remaining three studies found results consistent with additivity. While the limited available data are somewhat mixed, the evidence suggests that at least under some conditions the assumption of additivity does not hold in placebo analgesia. The concordance between mechanisms of the active analgesic and placebo analgesia may influence whether additivity occurs or not. However, more research using factorial designs is needed to disentangle the relationship between placebo analgesia and the active effect of analgesic treatments.
Topics: Analgesia; Biomedical Research; Humans; Pain; Placebo Effect
PubMed: 30146056
DOI: 10.1016/bs.irn.2018.07.021 -
Nature Human Behaviour Dec 2019Medical treatments typically occur in the context of a social interaction between healthcare providers and patients. Although decades of research have demonstrated that...
Medical treatments typically occur in the context of a social interaction between healthcare providers and patients. Although decades of research have demonstrated that patients' expectations can dramatically affect treatment outcomes, less is known about the influence of providers' expectations. Here we systematically manipulated providers' expectations in a simulated clinical interaction involving administration of thermal pain and found that patients' subjective experiences of pain were directly modulated by providers' expectations of treatment success, as reflected in the patients' subjective ratings, skin conductance responses and facial expression behaviours. The belief manipulation also affected patients' perceptions of providers' empathy during the pain procedure and manifested as subtle changes in providers' facial expression behaviours during the clinical interaction. Importantly, these findings were replicated in two more independent samples. Together, our results provide evidence of a socially transmitted placebo effect, highlighting how healthcare providers' behaviour and cognitive mindsets can affect clinical interactions.
Topics: Adolescent; Adult; Attitude; Empathy; Facial Expression; Female; Galvanic Skin Response; Humans; Interpersonal Relations; Male; Motivation; Pain; Physical Stimulation; Placebo Effect; Skin Cream; Young Adult
PubMed: 31636406
DOI: 10.1038/s41562-019-0749-5 -
European Journal of Sport Science Apr 2020
Topics: Exercise; Humans; Placebo Effect; Research Design; Sports
PubMed: 32299310
DOI: 10.1080/17461391.2020.1757682