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European Journal of Sport Science Apr 2020Placebo and nocebo effects are a factor in sports performance. However, the majority of published studies in sport science are descriptive and speculative regarding... (Review)
Review
Placebo and nocebo effects are a factor in sports performance. However, the majority of published studies in sport science are descriptive and speculative regarding mechanisms. It is therefore not unreasonable for the sceptic to argue that placebo and nocebo effects in sport are illusory, and might be better explained by variations in phenomena such as motivation. It is likely that, in sport at least, placebo and nocebo effects will remain in this empirical grey area until researchers provide stronger mechanistic evidence. Recent research in neuroscience has identified a number of consistent, discrete and interacting neurobiological and physiological pathways associated with placebo and nocebo effects, with many studies reporting data of potential interest to sport scientists, for example relating to pain, fatigue and motor control. Findings suggest that placebos and nocebos result in activity of the opioid, endocannabinoid and dopamine neurotransmitter systems, brain regions including the motor cortex and striatum, and measureable effects on the autonomic nervous system. Many studies have demonstrated that placebo and nocebo effects associated with a treatment, for example an inert treatment presented as an analgesic or stimulant, exhibit mechanisms similar or identical to the verum or true treatment. Such findings suggest the possibility of a wide range of distinct placebo and nocebo mechanisms that might influence sports performance. In the present paper, we present some of the findings from neuroscience. Focussing on fatigue as an outcome and caffeine as vehicle, we propose three approaches that researchers in sport might incorporate in their studies in order to better elucidate mechanisms of placebo/nocebo effects on performance.
Topics: Athletic Performance; Caffeine; Fatigue; Humans; Neural Pathways; Nocebo Effect; Placebo Effect
PubMed: 31573836
DOI: 10.1080/17461391.2019.1675765 -
Philosophical Transactions of the Royal... Jun 2011Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical conceptualization of the placebo effect... (Review)
Review
Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical conceptualization of the placebo effect remains poorly developed. Substantial mechanistic research on this phenomenon has proceeded with little guidance by any systematic theoretical paradigm. This review seeks to present a theoretical perspective on the formation of placebo responses. We focus on information processing, and argue that different kinds of learning along with individuals' genetic make-up evolved as the proximate cause for triggering behavioural and neural mechanisms that enable the formation of individual expectations and placebo responses. Conceptualizing the placebo effect in terms of learning offers the opportunity for facilitating scientific investigation with a significant impact on medical care.
Topics: Humans; Learning; Models, Psychological; Placebo Effect; Research Design; Signal Transduction
PubMed: 21576143
DOI: 10.1098/rstb.2010.0398 -
Medicine Apr 2016This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized... (Meta-Analysis)
Meta-Analysis Review
This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.
Topics: Patient Safety; Placebo Effect; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 27124060
DOI: 10.1097/MD.0000000000003516 -
Clinical Pharmacology and Therapeutics Feb 2015The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments... (Review)
Review
The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments that directly target biological mechanisms. The shortcomings of randomized clinical trials are currently discussed along with potential improvements of trial designs. In this review we explain how utilizing knowledge from the placebo and nocebo mechanisms literature could improve the information that can be obtained from randomized clinical trials. We present three major challenges in randomized clinical trials: (i) increasing placebo effects, (ii) variability of the placebo effect, and (iii) risk of un-blinding. We then explain how recent placebo and nocebo studies of effects of verbal suggestion, expectancy, and emotions may improve understanding and discussion of increasing placebo effects, account/control for large parts of the variability of placebo effects, and suggest ways to improve blinding in future trials.
Topics: Humans; Nocebo Effect; Physician-Patient Relations; Placebo Effect; Randomized Controlled Trials as Topic; Suggestion
PubMed: 25670519
DOI: 10.1002/cpt.31 -
Philosophical Transactions of the Royal... Jun 2011Laboratory research recently has greatly enhanced the understanding of placebo and nocebo effects by identifying specific neuromodulators and brain areas associated with... (Review)
Review
Laboratory research recently has greatly enhanced the understanding of placebo and nocebo effects by identifying specific neuromodulators and brain areas associated with them. However, little progress has been made in translating this knowledge into improved patient care. Here, we discuss the limitations in our knowledge about placebo (and nocebo) effects and the need for translational research with the aim of guiding physicians in maximizing placebo effects and minimizing nocebo effects in their routine clinical practice. We suggest some strategies for how, when and why interventions to promote beneficial placebo responses might be administered in the clinical setting.
Topics: Health Knowledge, Attitudes, Practice; Humans; Placebo Effect; Placebos; Research Design; Translational Research, Biomedical
PubMed: 21576150
DOI: 10.1098/rstb.2010.0399 -
Philosophical Transactions of the Royal... Jun 2011Using a comparative analysis of Navajo healing ceremonials, acupuncture and biomedical treatment, this essay examines placebo studies and ritual theory as mutually... (Review)
Review
Using a comparative analysis of Navajo healing ceremonials, acupuncture and biomedical treatment, this essay examines placebo studies and ritual theory as mutually interpenetrating disciplines. Healing rituals create a receptive person susceptible to the influences of authoritative culturally sanctioned 'powers'. The healer provides the sufferer with imaginative, emotional, sensory, moral and aesthetic input derived from the palpable symbols and procedures of the ritual process-in the process fusing the sufferer's idiosyncratic narrative unto a universal cultural mythos. Healing rituals involve a drama of evocation, enactment, embodiment and evaluation in a charged atmosphere of hope and uncertainty. Experimental research into placebo effects demonstrates that routine biomedical pharmacological and procedural interventions contain significant ritual dimensions. This research also suggests that ritual healing not only represents changes in affect, self-awareness and self-appraisal of behavioural capacities, but involves modulations of symptoms through neurobiological mechanisms. Recent scientific investigations into placebo acupuncture suggest several ways that observations from ritual studies can be verified experimentally. Placebo effects are often described as 'non-specific'; the analysis presented here suggests that placebo effects are the 'specific' effects of healing rituals.
Topics: Acupuncture Therapy; Ceremonial Behavior; Humans; Indians, North American; Medicine, Traditional; Placebo Effect; Religion and Medicine
PubMed: 21576142
DOI: 10.1098/rstb.2010.0385 -
JAMA Network Open Jul 2022Nonspecific effects, particularly placebo effects, are thought to contribute significantly to the observed effect in surgical trials. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Nonspecific effects, particularly placebo effects, are thought to contribute significantly to the observed effect in surgical trials.
OBJECTIVE
To estimate the proportion of the observed effect of surgical treatment that is due to nonspecific effects (including the placebo effect).
DATA SOURCES
Published Cochrane reviews and updated, extended search of MEDLINE, Embase, and CENTRAL until March 2019.
STUDY SELECTION
Published randomized placebo-controlled surgical trials and trials comparing the effect of the same surgical interventions with nonoperative controls (ie, no treatment, usual care, or exercise program).
DATA EXTRACTION AND SYNTHESIS
Pairs of authors independently screened the search results, assessed full texts to identify eligible studies and the risk of bias of included studies, and extracted data. The proportion of all nonspecific effects was calculated as the change in the placebo control divided by the change in the active surgery and pooled in a random-effect meta-analysis. To estimate the magnitude of the placebo effect, we pooled the difference in outcome between placebo and nonoperative controls and used metaregression to estimate the association between the type of control group and the treatment effect (difference between the groups), adjusting for risk of bias, sample size, and type of outcome.
MAIN OUTCOMES AND MEASURES
Between- and within-group effect sizes expressed as Hedges g.
RESULTS
In this review, 100 trials were included comprising data from 62 trials with placebo controls (3 also included nonoperative controls), and 38 trials with nonoperative controls (32 interventions; 10 699 participants). Risk of bias across trials was comparable except for performance and detection bias, which was high in trials with nonoperative controls. The mean nonspecific effects accounted for 67% (95% CI, 61% to 73%) of the observed change after surgery; however, this varied widely between different procedures. The estimated surgical placebo effect had a standardized mean difference (SMD) of 0.13 (95% CI, -0.26 to 0.51). Trials with placebo and nonoperative controls found comparable treatment effects (SMD, -0.09 [95% CI, -0.35 to 0.18]; 15 interventions; 73 between-group effects; adjusted analysis: SMD, -0.11 [95% CI, -0.37 to 0.15]).
CONCLUSIONS AND RELEVANCE
In this review, the change in health state after surgery was composed largely of nonspecific effects, but no evidence supported a large placebo effect. Placebo-controlled surgical trials may be redundant when trials with nonoperative controls consistently report no substantial association from surgery compared with nonoperative treatment.
Topics: Control Groups; Exercise; Humans; Placebo Effect
PubMed: 35895060
DOI: 10.1001/jamanetworkopen.2022.23903 -
International Journal of Molecular... Apr 2022The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations... (Review)
Review
The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.
Topics: Analgesia; Endocrine System; Humans; Pain; Pain Management; Placebo Effect
PubMed: 35457014
DOI: 10.3390/ijms23084196 -
Scientific Reports Oct 2022The aim of this study was to investigate the physiological effects of compression tights on blood flow following exercise and to assess if the placebo effect is...
The aim of this study was to investigate the physiological effects of compression tights on blood flow following exercise and to assess if the placebo effect is responsible for any acute performance or psychological benefits. Twenty-two resistance-trained participants completed a lower-body resistance exercise session followed by a 4 h recovery period. Participants were assigned a post-exercise recovery intervention of either compression tights applied for 4 h (COMP), placebo tablet consumed every hour for 4 h (PLA) or control (CON). Physiological (markers of venous return, muscle blood flow, blood metabolites, thigh girth), performance (countermovement jump, isometric mid-thigh pull), and psychological measures (perceived muscle soreness, total quality of recovery) were collected pre-exercise, immediately post-exercise, at 30 (markers of venous return and muscle blood flow) and 60 min (blood metabolites, thigh girth and psychological measures) intervals during 4 h of recovery, and at 4 h, 24 h and 48 h post-exercise. No significant (P > 0.05) differences were observed between interventions. However, effect size analysis revealed COMP enhanced markers of venous return, muscle blood flow, recovery of performance measures, psychological measures and reduced thigh girth compared to PLA and CON. There were no group differences in blood metabolites. These findings suggest compression tights worn after resistance exercise enhance blood flow and indices of exercise recovery, and that these benefits were not due to a placebo effect.
Topics: Exercise; Humans; Muscle, Skeletal; Myalgia; Placebo Effect; Polyesters; Thigh
PubMed: 36202885
DOI: 10.1038/s41598-022-21029-2 -
Biology Letters Nov 2017The placebo effect is widely recognized but important questions remain, for example whether the capacity to respond to a placebo is an evolved, and potentially... (Review)
Review
The placebo effect is widely recognized but important questions remain, for example whether the capacity to respond to a placebo is an evolved, and potentially ubiquitous trait, or an unpredictable side effect of another evolved process. Understanding this will determine the degree to which the physiology underlying placebo effects might be manipulated or harnessed to optimize medical treatments. We argue that placebo effects are cases of phenotypic plasticity where once predictable cues are now unpredictable. Importantly, this explains why placebo-like effects are observed in less complex organisms such as worms and flies. Further, this indicates that such species present significant opportunities to test hypotheses that would be ethically or pragmatically impossible in humans. This paradigm also suggests that data informative of human placebo effects pre-exist in studies of model organisms.
Topics: Animals; Biological Variation, Population; Cues; Humans; Models, Animal; Placebo Effect
PubMed: 29187606
DOI: 10.1098/rsbl.2017.0585