Placebo response to sham electroacupuncture in patients with chronic functional constipation: A secondary analysis.

BACKGROUND: Chronic severe functional constipation is a common disease that requires novel and effective treatment strategies. Acupuncture might constitute a promising therapeutic approach for chronic constipation, but it reportedly engenders an enhanced placebo response. Herein, we aimed to determine the magnitude of the placebo responses to electroacupuncture for constipation and identify its influencing factors. METHODS: In this secondary analysis of a multicenter randomized trial, patients were randomized to a sham electroacupuncture group, which was administered for 8 weeks in 24 sessions of superficial needling at nonacupoints. The placebo response rates were assessed using three responder criteria: ≥3 complete spontaneous bowel movements per week (CSBMs/week), overall CSBM, and sustained CSBM. Logistic regression with backward selection method was employed to identify the potential factors that affected the placebo response. KEY RESULTS: Overall, 539 patients were included in the study. The placebo response rate was 10.58%, 9.46%, and 9.09% according to the three aforementioned criteria, respectively. Those who exhibited more CSBMs/week at baseline were more likely to respond to sham electroacupuncture. Among patients with more than one CSBM per week at baseline, the response rates for achieving the criteria of ≥3 CSBMs per week, overall CSBM, and sustained CSBM were 25.40%, 30.16%, and 22.22%. CONCLUSIONS AND INFERENCE: Electroacupuncture did not demonstrate a large placebo response in functional constipation treatment. The number of CSBMs at baseline may be a moderator of the placebo response to sham electroacupuncture. Thus, superficial needling sham acupuncture may be considered an ideal sham control for clinical trials of chronic constipation.

Comparison of low-level laser therapy and standard treatment for temporomandibular disorders: An assessment of therapeutic and placebo effects.

BACKGROUND: Despite extensive research on the use of low-power lasers for TMD treatment, the extent of their effectiveness remains uncertain. OBJECTIVE: This study aimed to investigate the therapeutic or placebo effect of LLLT for TMD, and to compare it with standard treatment methods. A unique aspect of this study was the inclusion of a control group that received only standard treatment, allowing for an assessment of the placebo effect of LLLT. METHODS: A total of 42 patients with TMD were referred to Kerman Dental School Pain Clinic and were randomly assigned to three groups: group A received LLLT, group B was a placebo group and group C was a control group that received only standard treatment. The laser groups received gallium-aluminium-arsenide laser treatment twice a week for 10 sessions. Patients' jaw movement rate indicators and VAS index were evaluated at the start of treatment, and indicators were re-recorded every week for 5 weeks. SPSS 21 was used for statistical analysis, including ANOVA and Tukey's post hoc tests for inter-group comparisons. The repeated measurement test was used to analyse the data. RESULTS: All groups showed significant improvement in VAS indicators (p = .0001), lateral jaw movements (p = .0001), forward jaw movement (p = .007) but not for maximum mouth opening. No significant difference was observed between the groups at the end of the study (p = .000). CONCLUSION: Our study provides insights into LLLT's effectiveness for TMD, suggesting it cannot replace standard treatment alone. These findings contribute to the literature and emphasise the importance of including a control group in future studies to assess the placebo effect of LLLT.

Homeopathy is not placebo effect: proof of scientific evidence for homeopathy

Homeopathy has been a medical practice recognized worldwide for more than two centuries, performing care, teaching and research activities in several health institutions and medical schools. It employs a clinical approach based on heterodox and complementary scientific principles (principle of therapeutic similitude, homeopathic pathogenetic experimentation, use of individualized medicines and dynamized or potentiated doses), with the aim of awakening a curative response in the body against its own disorders and/or diseases. Based on different premises from those used by conventional medical practice, homeopathy is often the target of unfounded and widespread criticism from individuals who systematically deny homeopathic assumptions and any scientific evidence that proves them due to their pseudoskeptical and pseudoscientific stance, which prevents a correct and bias-free analysis. In order to enlighten doctors, researchers, health professionals and the general public, demystifying culturally rooted dogmatic positions and the pseudoskeptical fallacies that "there is no scientific evidence for homeopathy" and "homeopathy is placebo effect", the Technical Chamber of Homeopathy of the Regional Council of Medicine of the State of São Paulo (TC-Homeopathy, Cremesp) prepared the "Special Dossier: Scientific Evidence for Homeopathy" in 2017, made available in three independent editions (online in Portuguese and English; printed in Portuguese) in the Revista de Homeopatia (São Paulo). Then, the dossier was published in Spanish in the La Homeopatía de México journal in 2023 in an edition commemorating the journal's 90th anniversary. Encompassing nine narrative reviews on the various lines of homeopathy research and containing hundreds of scientific articles describing experimental and clinical studies, the Dossier highlighted the state of the art of homeopathic science. Proving and expanding this scientific evidence in 13 chapters, the current work aims to update and clarify knowledge in the area. In addition to elucidating the epistemological premises of the homeopathic model in detail, the work describes the various aspects of basic and clinical research which endorse homeopathic practice and treatment in a continuum of information, data and bibliographic references. The work discusses various topics related to research in homeopathy, covering everything from "homeopathic clinical epidemiology" to "pseudoskeptic and pseudoscientific strategies used in attacks on homeopathy", including "pharmacological basis of the principle of similitude", "experimental studies in biological models", "randomized controlled clinical trials", "systematic reviews, meta-analyses and global reports" and "observational studies", among others. In view of the fact that it becomes fruitless and tiring to describe and analyze all the studies and experiments from the different research lines, we suggest and systematize in the different chapters for those who want to delve deeper into the areas of interest, bibliographical surveys of existing literature through the different databases. As we reiterate throughout the work, despite the difficulties and limitations that exist in developing research in homeopathy due to both methodological aspects and the lack of institutional and financial support, the set of experimental and clinical studies described is indisputable proof that "there is scientific evidence for homeopathy" and "homeopathy is not placebo effect", contrary to falsely disseminated prejudice. However, new studies must continue to be developed to improve clinical practice and elucidate peculiar aspects of the homeopathic paradigm. Acting as an integrative and complementary therapy to other specialties, homeopathy can add efficacy, effectiveness, efficiency and safety to medical practice, acting in a curative and preventive manner, reducing symptomatic manifestations and the predisposition to falling ill, with low cost and minimal adverse events, helping doctors to fulfill their "highest and only mission, which is to make sick people healthy, which is called healing" (Samuel Hahnemann, Organon of Medicine, § 1).

La homeopatía no es efecto placebo: comprobación de las evidencias científicas en homeopatía / Homeopathy is not Placebo Effect: Proof of Scientific Evidence for Homeopathy

La Homeopatía ha sido una práctica médica de renombre mundial durante más de dos siglos, desarrollando actividades asistenciales, docentes y de investigación en varias instituciones de salud y escuelas de medicina. Emplea un enfoque clínico basado en principios científicos heterodoxos y complementarios (principio de similitud terapéutica, experimentación patogénica homeopática, uso de medicamentos individualizados y dosis dinamizadas), con el objetivo de despertar una respuesta curativa del organismo frente a sus propios trastornos o enfermedades. Partiendo de premisas diferentes a las empleadas por la práctica médica convencional, la Homeopatía suele ser objeto de críticas infundadas y generalizadas por parte de individuos que niegan sistemáticamente los supuestos homeopáticos y cualquier evidencia científica que los demuestre porque tienen una postura pseudoescéptica y pseudocientífica que impide un análisis correcto y desprejuiciado. Son "pseudoescépticos" disfrazados de "pseudocientíficos". Ilustrar a médicos, investigadores, profesionales de la salud y al público en general, desmitificando las posturas dogmáticas culturalmente arraigadas y las falacias pseudoescépticas de que "no hay evidencia científica en la Homeopatía" y "la Homeopatía es un efecto placebo", en 2017, la Cámara Técnica de Homeopatía del Consejo Regional de Medicina del Estado de São Paulo (CT-Homeopatía, Cremesp) elaboró el "Dossier Especial: Evidencia Científica en Homeopatía", disponible en tres ediciones independientes (en línea en portugués e inglés; impresa en portugués) en la Revista de Homeopatía (São Paulo). En 2023, el dossier fue publicado en español en la revista La Homeopatía de México, en una edición conmemorativa del 90 aniversario de la revista. Abarcando nueve revisiones narrativas sobre las diversas líneas de investigación en Homeopatía, que contienen cientos de artículos científicos que describen estudios experimentales y clínicos, el dossier destacó el estado del arte de la ciencia homeopática. Demostrando y ampliando esta evidencia científica, el presente trabajo ("La Homeopatía no es Efecto Placebo": Comprobación de las Evidencias Científicas en Homeopatía) pretende esclarecer los conocimientos en el área en trece capítulos. Además de dilucidar en detalle las premisas epistemológicas del modelo homeopático, el trabajo describe, en un continuo de información, datos y referencias bibliográficas, los diversos aspectos de la investigación básica y clínica que avalan la práctica y el tratamiento homeopático. Discutiendo diversos temas relacionados con la investigación en Homeopatía, el libro aborda desde la "epidemiología clínica homeopática" hasta las "estrategias pseudoescépticas y pseudocientíficas utilizadas en los ataques a la Homeopatía", pasando por el "fundamento farmacológico del principio de similitud", "estudios experimentales en modelos biológicos", "ensayos clínicos controlados aleatorizados", "revisiones sistemáticas, metaanálisis e informes globales" y "estudios observacionales", entre otros. Como hemos reiterado a lo largo del libro, a pesar de las dificultades y limitaciones en el desarrollo de la investigación en Homeopatía, tanto por aspectos metodológicos como por la ausencia de apoyo institucional y financiero, el conjunto de estudios experimentales y clínicos descritos es una prueba irrefutable de que "existen evidencias científicas en Homeopatía" y "la Homeopatía no es efecto placebo", contrariamente al prejuicio falsamente difundido. Actuando como terapia integradora y complementaria a otras especialidades, la Homeopatía puede agregar eficacia, efectividad, eficiencia y seguridad a la práctica médica, reduciendo las manifestaciones sintomáticas y la predisposición a la enfermedad, con bajo costo y mínimos eventos adversos.

Placebo response in sham-acupuncture-controlled trials for migraine: A systematic review and meta-analysis.

AIM: To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment. METHODS: Randomized controlled trials with sham acupuncture as a control in migraine treatment were searched in four English databases from inception to September 1, 2022. The primary outcome was placebo response rate. Secondary outcomes were migraine symptoms, emotional condition, and quality of life. Factors associated with placebo response were also explored. Results were combined using risk difference (RD) or standardized mean difference (SMD) and 95% confidence interval (CI) with a random effects model. RESULTS: The final analysis included 21 studies involving 1177 patients. The pooled response rate of sham acupuncture was 0.34 (RD, 95% CI 0.23-0.45, I2 89.8%). The results (SMD [95% CI]) showed significant improvements in migraine symptoms (pain intensity -0.56 [-0.73 to -0.38], and episode conditions -0.55 [-0.75 to -0.35]); emotional condition (anxiety scale -0.49 [-0.90 to -0.08] and depression scale -0.21 [-0.40 to -0.03]); and quality of life on the Migraine-Specific Quality-of-Life Questionnaire (restrictive 0.78 [0.61-0.95]; preventive 0.52 [0.35-0.68]; and emotional 0.45 [0.28-0.62]) and on the Medical Outcomes Study Short-Form (physical 0.48 [0.34-0.62] and mental 0.21 [0.02-0.41]). Only acupuncture treatment frequency had a significant impact on the placebo response rate (RD 0.49 vs. 0.14; p = 0.00). CONCLUSIONS: The effect sizes for placebo response of sham acupuncture varied across migraine treatment trials. Further studies should routinely consider adjusting for a more complete set of treatment factors.

Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis.

BACKGROUND: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear. OBJECTIVE: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects. SEARCH STRATEGY: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included. DATA EXTRACTION AND ANALYSIS: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response. RESULTS: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response. CONCLUSION: Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.

"Do Not Mix Apples with Oranges" to Avoid Misinterpretation of Placebo Effects in Manual Therapy: The Risk Is Resulting in a Fruit Basket. Comment on Molina-Àlvarez et al. Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2022, 19, 14021.

We read with interest the systematic review with the meta-analysis by Miguel Molina-Álvarez et al. [...].

Reply to Rossettini et al. "Do Not Mix Apples with Oranges" to Avoid Misinterpretation of Placebo Effects in Manual Therapy: The Risk Is Resulting in a Fruit Basket. Comment on "Molina-Álvarez et al. Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2022, 19, 14021".

We have thoroughly reviewed and carefully analyzed the points raised in the comment titled: "Do not mix apples with oranges" to avoid misinterpretation of placebo effects in manual therapy: the risk is resulting in a fruit basket [...].

The Optimal Learning Cocktail for Placebo Analgesia: A Randomized Controlled Trial Comparing Individual and Combined Techniques.

This study investigated for the first time the effects of individual and combined application of 3 learning techniques (verbal suggestions, classical conditioning, and observational learning) on placebo analgesia and extinction. Healthy participants (N = 206) were assigned to 8 different groups in which they were taught through either a verbal suggestion, a conditioning paradigm, a video observing someone, or any combination thereof that a placebo device (inactive transcutaneous electric nerve stimulation [TENS]) was capable of alleviating heat pain, whereas one group did not (control). Placebo analgesia was quantified as the within-group difference in experienced pain when the placebo device was (sham) 'activated' or 'inactivated' during equal pain stimuli, and compared between groups. Placebo analgesia was induced in groups with 2 or 3 learning techniques. Significantly stronger placebo analgesia was induced in the combination of all 3 learning techniques as compared to the individual learning techniques or control condition, underlining the additional contribution of 3 combined techniques. Extinction did not differ between groups. Furthermore, pain expectancies, but not state anxiety or trust, mediated placebo analgesia. Our findings emphasize the added value of combining 3 learning techniques to optimally shape expectancies that lead to placebo analgesia, which can be used in experimental and clinical settings. PERSPECTIVE: This unique experimental study compared the individual versus combined effects of 3 important ways of learning (verbal suggestions, classical conditioning, and observational learning) on expectation-based pain relief. The findings indicate that placebo effects occurring in clinical practice could be optimally strengthened if healthcare providers apply these techniques in combination.

Placebo effects contribute to brief online mindfulness interventions for chronic pain: results from an online randomized sham-controlled trial.

ABSTRACT: Mindfulness apps are becoming popular treatments for chronic pain and mental health, despite mixed evidence supporting their efficacy. Furthermore, it is unclear whether improvements in pain are due to mindfulness-specific effects or placebo effects because no trials have compared mindfulness against a sham control. The objective of this study was to compare mindfulness against 2 sham conditions with differing proximity to mindfulness to characterize the relative contributions of mindfulness-specific and nonspecific processes on chronic pain. We assessed changes in pain intensity and unpleasantness and mindfulness-specific and nonspecific pain-related processes in 169 adults with chronic or recurrent pain randomized to receive a single 20-minute online session of mindfulness, specific sham mindfulness, general sham mindfulness, or audiobook control. Mindfulness was not superior to shams for reducing pain intensity or unpleasantness, and no differential engagement of theorized mindfulness-specific processes was observed. However, mindfulness and both shams reduced pain unpleasantness relative to audiobook control, with expectancy most strongly associated with this effect. Sham specificity had no influence on expectancy or credibility ratings, pain catastrophizing, or pain effects. These findings suggest that improvements in chronic pain unpleasantness following a single session of online-delivered mindfulness meditation may be driven by placebo effects. Nonspecific treatment effects including placebo expectancy and pain catastrophizing may drive immediate pain attenuation rather than theorized mindfulness-specific processes themselves. Further research is needed to understand whether mindfulness-specific effects emerge after longer durations of online training.

Six-Month Follow-up of a Trial of Spinal Cord Burst Stimulation vs Placebo Stimulation and Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery.

This follow-up study examines back pain­related disability at 6 months following a randomized trial of spinal cord burst stimulation for chronic radicular pain after lumbar spine surgery.

Yoga and massage are associated with small experimental placebo effects in chronic orofacial pain.

BACKGROUND: Complementary and Integrative Health Approaches (CIHA), including but not limited to, natural products and Mind and Body Practices (MBPs), are promising non-pharmacological adjuvants to the arsenal of pain management therapeutics. We aim to establish possible relationships between use of CIHA and the capacity of descending pain modulatory system in the form of occurrence and magnitude of placebo effects in a laboratory setting. METHODS: This cross-sectional study investigated the relationship between self-reported use of CIHA, pain disability, and experimentally induced placebo hypoalgesia in chronic pain participants suffering from Temporomandibular Disorders (TMD). In the 361 enrolled TMD participants, placebo hypoalgesia was measured using a well-established paradigm with verbal suggestions and conditioning cues paired with distinct heat painful stimulations. Pain disability was measured with the Graded Chronic Pain Scale, and use of CIHA were recorded with a checklist as part of the medical history. RESULTS: Use of physically oriented MBPs (e.g., yoga and massage) was associated with reduced placebo effects (F1,2110.44 = 23.15, p < 0.001, Cohen's d = 0.171). Further, linear regressions indicated that greater number of physically oriented MBPs predicted smaller placebo effects (ß = -0.17, p = 0.002), and less likelihood of being a placebo responder (OR = 0.70, p = 0.004). Use of psychologically oriented MBPs and natural product were not associated with placebo effects magnitude and responsiveness. CONCLUSIONS: Our findings suggest that use of physically oriented CIHA was associated with experimental placebo effects possibly through an optimized capability to recognize distinct somatosensorial stimulations. Future research is needed to understand the mechanisms underlying placebo-induced pain modulation in CIHA users. SIGNIFICANCE: Chronic pain participants who use physically oriented mind-body practices, such as yoga and massage, demonstrated attenuated experimentally induced placebo hypoalgesia in comparison with those who do not use them. This finding disentangled the relationship between use of complementary and integrative approaches and placebo effects, providing the potential therapeutic perspective of endogenous pain modulation in chronic pain management.

Placebo effects on cutaneous pain and itch: a systematic review and meta-analysis of experimental results and methodology.

ABSTRACT: Placebo effects, positive treatment outcomes that go beyond treatment processes, can alter sensations through learning mechanisms. Understanding how methodological factors contribute to the magnitude of placebo effects will help define the mechanisms by which these effects occur. We conducted a systematic review and meta-analysis of experimental placebo studies in cutaneous pain and itch in healthy samples, focused on how differences in methodology contribute to the resulting placebo effect magnitude. We conducted meta-analyses by learning mechanism and sensation, namely, for classical conditioning with verbal suggestion, verbal suggestion alone, and observational learning, separately for pain and itch. We conducted subgroup analyses and meta-regression on the type of sensory stimuli, placebo treatment, number of acquisition and evocation trials, differences in calibrated intensities for placebo and control stimuli during acquisition, age, and sex. We replicated findings showing that a combination of classical conditioning with verbal suggestion induced larger placebo effects on pain ( k = 68, g = 0 . 59) than verbal suggestion alone ( k = 39, g = 0.38) and found a smaller effect for itch with verbal suggestion alone ( k = 7, g = 0.14). Using sham electrodes as placebo treatments corresponded with larger placebo effects on pain than when topical gels were used. Other methodological and demographic factors did not significantly affect placebo magnitudes. Placebo effects on pain and itch reliably occur in experimental settings with varied methods, and conditioning with verbal suggestion produced the strongest effects. Although methods may shape the placebo effect to some extent, these effects appear robust overall, and their underlying learning mechanisms may be harnessed for applications outside the laboratory.

Homeopatia não é efeito placebo: comprovação das evidências científicas da homeopatia / Homeopathy is not a placebo effect: proof of scientific evidence for homeopathy

A homeopatia é uma prática médica reconhecida mundialmente há mais de dois séculos, desenvolvendo atividades de assistência, ensino e pesquisa em diversas instituições de saúde e faculdades de medicina. Emprega uma abordagem clínica baseada em princípios científicos heterodoxos e complementares (princípio da similitude terapêutica, experimentação patogenética homeopática, uso de doses dinamizadas e medicamentos individualizados), com o objetivo de despertar uma resposta curativa do organismo contra seus próprios distúrbios ou doenças. Baseando-se em premissas distintas das empregadas pela prática médica convencional, a homeopatia é muitas vezes alvo de críticas infundadas e generalizadas por parte de indivíduos que, sistematicamente, negam os pressupostos homeopáticos e quaisquer evidências científicas que os comprovem, em vista de uma postura pseudocética e pseudocientífica que impede uma análise correta e isenta de preconceitos. Para elucidar médicos, pesquisadores, profissionais de saúde e o público em geral, desmistificando posturas dogmáticas culturalmente arraigadas e as falácias pseudocéticas de que "não existem evidências científicas em homeopatia" e "homeopatia é efeito placebo", em 2017, a Câmara Técnica de Homeopatia do Conselho Regional de Medicina do Estado de São Paulo (CT-Homeopatia, Cremesp) elaborou o "Dossiê Especial: Evidências Científicas em Homeopatia", disponibilizado em três edições independentes (online em português e inglês; impressa em português) na Revista de Homeopatia (São Paulo). Em 2023, o dossiê foi publicado em espanhol na revista La Homeopatía de México, em edição de livre acesso comemorativa do 90° aniversário do periódico. Englobando nove revisões narrativas sobre as diversas linhas da pesquisa em homeopatia, contendo centenas de artigos científicos que descrevem estudos experimentais e clínicos, o dossiê destacou o estado da arte da ciência homeopática. Comprovando e ampliando essas evidências científicas, o atual compêndio visa atualizar e esclarecer o conhecimento na área em treze capítulos. Além de elucidar, em detalhes, as premissas epistemológicas do modelo homeopático, a obra descreve, num continuum de informações, dados e referências bibliográficas, os diversos aspectos da pesquisa básica e clínica que endossam a prática e o tratamento homeopático. Discorrendo sobre temas diversos relacionados à pesquisa em homeopatia, o relatório aborda desde a "epidemiologia clínica homeopática" até as "estratégias pseudocéticas e pseudocientíficas usadas em ataques à homeopatia", passando por "fundamentação farmacológica do princípio da similitude", "estudos experimentais em modelos biológicos", "ensaios clínicos controlados randomizados", "revisões sistemáticas, metanálises e relatórios globais" e "estudos observacionais", dentre outros. Em vista de que se torna infrutífero e cansativo descrever a analisar todos os estudos e experimentos das diversas linhas de pesquisa, sugerimos e sistematizamos nos diversos capítulos, aos que queiram se aprofundar nas áreas de interesse, levantamentos bibliográficos da literatura existente através dos distintos bancos ou bases de dados. Como reiteramos ao longo da obra, apesar das dificuldades e limitações existentes no desenvolvimento de pesquisas em homeopatia, tanto pelos aspectos metodológicos quanto pela ausência de apoio institucional e financeiro, o conjunto de estudos experimentais e clínicos descritos é prova inconteste de que "existem evidências científicas em homeopatia" e "homeopatia não é efeito placebo", ao contrário do preconceito falsamente disseminado. No entanto, novos estudos devem continuar a ser desenvolvidos, para aprimorar a prática clínica e elucidar aspectos singulares ao paradigma homeopático. Atuando como terapêutica integrativa e complementar às demais especialidades, a homeopatia pode acrescentar eficácia, efetividade, eficiência e segurança à prática médica, atuando de forma curativa e preventiva, diminuindo as manifestações sintomáticas e a predisposição ao adoecer, com baixo custo e eventos adversos mínimos.

Homeopathy is a medical practice recognized worldwide for more than two centuries, developing assistance, teaching and research activities in several health institutions and medical schools. It employs a clinical approach based on heterodox and complementary scientific principles (principle of therapeutic similitude, homeopathic pathogenetic experimentation, use of dynamized doses and individualized medicines), with the aim of awakening a curative response of the organism against its own disorders or diseases. Based on assumptions that are different from those employed by conventional medical practice, homeopathy is often the target of unfounded and generalized criticism by individuals who systematically deny homeopathic assumptions and any scientific evidence that proves them, in view of a pseudosceptical and pseudoscientific stance that prevents a correct analysis free of prejudice. To elucidate doctors, researchers, health professionals and the general public, demystifying culturally rooted dogmatic positions and the pseudoskeptical fallacies that "there isn't scientific evidence for homeopathy" and "homeopathy is a placebo effect", in 2017, the Technical Chamber of Homeopathy of the Regional Council of Medicine of the State of São Paulo (CT-Homeopathy, Cremesp) prepared the "Special Dossier: Scientific Evidence for Homeopathy", available in three independent editions (online in Portuguese and English; printed in Portuguese) in the Revista de Homeopatia ( São Paulo). In 2023, the dossier was published in Spanish in the journal La Homeopatía de México, in an open access edition commemorating the journal's 90th anniversary. Encompassing nine narrative reviews on the various lines of research in homeopathy, containing hundreds of scientific articles describing experimental and clinical studies, the dossier highlighted the state of the art of homeopathic science. Proving and expanding this scientific evidence, the current compendium aims to update and clarify knowledge in the area in thirteen chapters. In addition to elucidating, in details, the epistemological premises of the homeopathic model, the work describes the various aspects of basic and clinical research that endorse homeopathic practice and treatment, in a continuum of information, data and bibliographical references. Discussing various topics related to research in homeopathy, the report covers everything from "homeopathic clinical epidemiology" to "pseudosceptic and pseudoscientific strategies used in attacks on homeopathy", passing through "pharmacological foundations of the principle of similarity", "experimental studies in biological models", "randomized controlled trials", "systematic reviews, meta-analyses and global reports" and "observational studies", among others. In view of the fact that it becomes fruitless and tiring to describe and analyze all the studies and experiments of the different lines of research, we suggest and systematize in the chapters, to those who want to deepen in the areas of interest, bibliographical surveys of the existing literature through the different databases. As we reiterate throughout the work, despite the difficulties and limitations existing in the development of research in homeopathy, both due to methodological aspects and the lack of institutional and financial support, the set of experimental and clinical studies described is undisputed proof that "there is scientific evidence for homeopathy" and "homeopathy is not a placebo effect", contrary to falsely disseminated prejudice. However, new studies must continue to be developed to improve clinical practice and elucidate unique aspects of the homeopathic paradigm. Acting as an integrative and complementary therapy to other specialties, homeopathy can add efficacy, effectiveness, efficiency and safety to medical practice, acting in a curative and preventive way, reducing symptomatic manifestations and predisposition to illness, with low cost and minimal adverse events.

Homeopatia não é efeito placebo como demonstra o "dossiê: evidências científicas em homeopatia" elaborado pelo CREMESP e disponibilizado em edições trilingues de livre acesso / Homeopathy is not a placebo effect as demonstrated by the "dossier: scientific evidence in homeopathy" prepared by CREMESP and made available in free access trilingual editions

Ao discorrermos sobre a homeopatia, em diversas situações, frequentemente, notamos que as pessoas reagem com manifestações de desconfiança, questionando sua comprovação científica e a validade terapêutica do método. Proclamadas em todos os meios, de forma indistinta e reiterada, as falácias ou notícias falsas (fake news) de que "a homeopatia é efeito placebo" ou de que "não existem evidências científicas em homeopatia" acaba se incorporando ao inconsciente da coletividade, servindo como estratégias pseudocéticas para aumentar preconceitos e radicalizar posicionamentos contrários a essa prática médica bissecular. Fruto da desinformação ou negação dos estudos científicos que fundamentam o modelo homeopático em vários campos da pesquisa científica moderna, esses preconceitos se retroalimentam, periodicamente, com matérias e artigos depreciativos e contrários à homeopatia publicados nas mídias de massa (jornais, sites e revistas não científicas) e redes sociais, as quais, raramente, divulgam os trabalhos científicos com resultados favoráveis à homeopatia.

Espiritualidade aplicada à medicina / Spirituality applied to medicine / Espiritualidad aplicada a la medicina

Resumo Espiritualidade é a força que une os diferentes aspectos componentes do ser e, quando trabalhada, proporciona uma vivência harmônica e promove equilíbrio entre bem-estar físico, social e mental. Nesse sentido, objetivou-se abordar, secularmente, como a espiritualidade é vista na medicina, sua influência na saúde e a percepção de profissionais e pacientes acerca desse assunto. Para tanto, realizou-se revisão narrativa que priorizou buscas na plataforma PubMed por meio dos seguintes descritores: "medicine and spirituality and secularismo" e "placebo effect and spirituality and medicine". Em seguida foram analisadas fontes referenciadas pela leitura dos artigos primordiais. Percebeu-se que há confusão quanto ao uso do termo espiritualidade e que a capacidade e efetividade do cuidado espiritual prestado por profissionais da saúde são débeis, contrastando com inúmeros benefícios oferecidos por essa atenção, que é uma ferramenta para um trabalho mais ético e humano.

Abstract Spirituality is a uniting force between different constituents of the human being and, when exercised, provides a harmonious experience and promotes balance between physical, social, and mental well-being. As such, this narrative review proposes a secular approach to how spirituality is understood by medicine, its influence on health, and how it is perceived by professionals and patients. Bibliographic search was conducted on the PubMed database, using the following descriptors: "medicine and spirituality and secularism" and "placebo effect and spirituality and medicine." After reading the primary articles, the referenced sources were analyzed. Results show a confusion on how the term spirituality is used and a weak capacity and effectiveness with respect to the spiritual care provided by health personnel, thus ignoring the several benefits offered by such care, which is a tool for a more ethical and humane work.

Resumen La espiritualidad es la fuerza que une los diferentes componentes del ser y al estimularse proporciona una experiencia armoniosa, además de promover el equilibrio de bienestar físico, social y mental. Ante lo anterior, este texto tuvo por objetivo abordar cómo se ve secularmente la espiritualidad en la medicina, su influencia en la salud y la percepción de profesionales y pacientes sobre este tema. Para ello, se realizó una revisión narrativa en la base de datos PubMed utilizando los siguientes descriptores: "medicine and spirituality and secularismo" y "placebo effect and spirituality and medicine". Después, se analizaron las fuentes mediante la lectura de los artículos principales. Se encontró una confusión con relación al uso del término espiritualidad, y es deficiente la habilidad y eficacia del cuidado espiritual que brindan los profesionales de la salud, contrastando con los numerosos beneficios de este cuidado, una herramienta para un trabajo más ético y humanizado.

Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis.

Importance: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements. Objective: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention. Data Sources: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered. Study Selection: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders. Data Extraction and Synthesis: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model. Main Outcomes and Measures: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g). Results: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes. Conclusions and Relevance: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.

Avoiding nocebo and other undesirable effects in chiropractic, osteopathy and physiotherapy: An invitation to reflect.

INTRODUCTION: While the placebo effect is increasingly recognised as a contributor to treatment effects in clinical practice, the nocebo and other undesirable effects are less well explored and likely underestimated. In the chiropractic, osteopathy and physiotherapy professions, some aspects of historical models of care may arguably increase the risk of nocebo effects. PURPOSE: In this masterclass article, clinicians, researchers, and educators are invited to reflect on such possibilities, in an attempt to stimulate research and raise awareness for the mitigation of such undesirable effects. IMPLICATIONS: This masterclass briefly introduces the nocebo effect and its underlying mechanisms. It then traces the historical development of chiropractic, osteopathy, and physiotherapy, arguing that there was and continues to be an excessive focus on the patient's body. Next, aspects of clinical practice, including communication, the therapeutic relationship, clinical rituals, and the wider social and economic context of practice are examined for their potential to generate nocebo and other undesirable effects. To aid reflection, a model to reflect on clinical practice and individual professions through the 'prism' of nocebo and other undesirable effects is introduced and illustrated. Finally, steps are proposed for how researchers, educators, and practitioners can maximise positive and minimise negative clinical context.

Can contagious itch be affected by positive and negative suggestions?

Contagious itch can be evoked by observing people scratching. Verbal suggestions about to-be-received itch can influence itch intensity, as shown by placebo research, but it is unknown whether this extends to contagious itch. The current study aimed to replicate prior findings that listening to scratching and rubbing sounds elicits contagious itch, and to investigate whether suggestions can modulate this process. Healthy participants (n = 140) received positive or negative suggestions about itch in response to the sounds (aimed to decrease or increase expected itch, respectively), or no specific suggestions as a control. Participants listened to a number of audio fragments with scratching and rubbing sounds. The amount of expected itch as well as itch sensation after each audio fragment were measured by self-report. Suggestions had no effect on the expected itch. Both rubbing and scratching sounds significantly elicited itch in all groups. Scratching sounds induced more itch than rubbing sounds exclusively in the control group. These findings indicate that short suggestions might be not effective enough to modify the expectations of people regarding contagious itch. Furthermore, suggestions modulate contagious itch to some degree, but not in the hypothesized direction. Potential similarities and differences in the neurobiological mechanisms of contagious itch and nocebo effects are discussed.

The impact of expectancy on the efficacy of acupuncture treatment for postprandial distress syndrome: Secondary analysis of a randomized clinical trial.

BACKGROUND: Expectancy is an important source of the placebo effect. However, it is unclear whether this has an effect on the efficacy of acupuncture and sham acupuncture in the treatment of postprandial distress syndrome (PDS). AIM: To evaluate the effects of high expectancy (HE) and low expectancy (LE) on the efficacy of acupuncture and sham acupuncture in the treatment of PDS. METHODS: This post hoc secondary analysis used data from our previous randomized controlled trial. Patients were, respectively, enrolled in the HE group and LE group according to expectancy assessments. The composite primary outcomes were the response rate and the elimination rate after 4 weeks of treatment. Expectancy was considered a factor affecting the efficacy of acupuncture treatment only if both primary outcomes achieved significance. RESULTS: For the acupuncture group, the response rate was 84.5% in the HE group and 78.8% in the LE group (p = 0.458), and the elimination rate was 32.1% in the HE group and 21.2% in the LE group (p = 0.241). For the sham acupuncture group, the response rate at week 4 was 52.3% in the HE group and 53.1% in the LE group (p = 0.936), and the elimination rate at week 4 was 23.1% in the HE group and 10.6% in the LE group (p = 0.090). CONCLUSION: In this study, the response rate and elimination rate were higher in the high-expectancy group, but no conclusive evidence was found for an association between expectancy and the efficacy of acupuncture and sham acupuncture.