Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.788
Filtrar
1.
OMICS ; 25(1): 1-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33305994

RESUMO

Pharmacogenomics, nutrigenomics, vaccinomics, and the nascent field of plant omics are examples of variability science. They are embedded within an overarching framework of personalized medicine. Across these public health specialties, the significance and biology of the placebo response have been historically neglected. A placebo is any substance such as a sugar pill administered in the guise of medication, but one that does not have pharmacological activity. Placebos do have clinical effects, however, that can be substantive in magnitude and vary markedly from person-to-person depending, for example, on the type of disease, symptoms, or clinical trial design. Research over the past several decades attests to a genuine neurobiological basis for placebo effects. All drugs have placebo components that contribute to their overall treatment effect. Placebos are used in clinical trials as control groups to ascertain the net pharmacological effect of a drug candidate. Not only less well known but also relevant to rational therapeutics and personalized medicine is the nocebo. A nocebo effect occurs when an inert substance is administered in a context that induces negative expectations, worsening patients' symptoms. With the COVID-19 pandemic, there are high public expectations for new vaccines and medicines to end the contagion, while at the same time antiscience, post-truth, and antivaccine movements are worrisomely on the rise. These social movements, changes in public health cultures, and conditioned behavioral responses can trigger both placebo and nocebo effects. Hence, in clinical trials, forecasting and explaining placebo and nocebo variability are more important than ever for robust science and personalized health care. Against this overarching context, this article provides (1) a brief history of placebo and (2) a discussion on biology, mechanisms, and variability of placebo effects, and (3) discusses three emerging new concepts: placebogenomics, nocebogenomics, and augmented placebo, that is, the notion of a "placebo dose." We conclude with a roadmap for placebogenomics, its synergies with the nascent field of social pharmacology, and the ways in which a new taxonomy of drug and placebo variability can be anticipated in the next decade.


Assuntos
Ensaios Clínicos como Assunto , Efeito Placebo , Medicina de Precisão , Projetos de Pesquisa , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Relação Dose-Resposta a Droga , Genômica/métodos , Humanos , Efeito Nocebo , Avaliação de Resultados em Cuidados de Saúde , Medicina de Precisão/métodos , Medicina de Precisão/normas
2.
PLoS One ; 15(9): e0238533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966280

RESUMO

In this proof-of-concept study, we tested whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 participants were exposed to a nauseating stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and (in females) gastric activity could be verified. Using label-free tandem mass spectrometry, 74 differentially regulated proteins were identified as correlates of the placebo effect. Gene ontology (GO) enrichment analyses identified acute-phase proteins and microinflammatory proteins to be involved, and the identified GO signatures predicted day-adjusted scores of nausea indices in the placebo group. We also performed GO enrichment analyses of specific plasma proteins predictable by the experimental factors or their interactions and identified 'grooming behavior' as a prominent hit. Finally, Receiver Operator Characteristics (ROC) allowed to identify plasma proteins differentiating placebo responders from non-responders, comprising immunoglobulins and proteins involved in oxidation reduction processes and complement activation. Plasma proteomics is a promising tool to identify molecular correlates and predictors of the placebo effect in humans.


Assuntos
Proteínas Sanguíneas/análise , Náusea/sangue , Náusea/terapia , Efeito Placebo , Terapia por Acupuntura , Adulto , Terapia por Estimulação Elétrica , Feminino , Humanos , Masculino , Enjoo devido ao Movimento/sangue , Enjoo devido ao Movimento/terapia , Proteômica , Adulto Jovem
3.
JAMA Netw Open ; 3(9): e2013196, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936297

RESUMO

Importance: Large placebo responses in randomized clinical trials may keep effective medication from reaching the market. Primary outcome measures of clinical trials have shifted from patient-reported to objective outcomes, partly because response to randomized placebo treatment is thought to be greater in subjective compared with objective outcomes. However, a direct comparison of placebo response in subjective and objective outcomes in the same patient population is missing. Objective: To assess whether subjective patient-reported (pain severity) and objective inflammation (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]) outcomes differ in placebo response. Design, Setting, and Participants: The placebo arms of 5 double-blind, randomized, placebo-controlled clinical trials were included in this cross-sectional study. These trials were conducted internationally for 24 weeks or longer between 2005 and 2009. All patients with rheumatoid arthritis randomized to placebo (N = 788) were included. Analysis of data from these trials was conducted from March 27 to December 31, 2019. Intervention: Placebo injection. Main Outcomes and Measures: The difference (with 95% CIs) from baseline at week 12 and week 24 on a 0- to 100-mm visual analog scale to evaluate the severity of pain, CRP level, and ESR. Results: Of the 788 patients included in the analysis, 644 were women (82%); mean (SD) age was 51 (13) years. There was a statistically significant decrease in patient-reported pain intensity (week 12: -14 mm; 95% CI, -12 to -16 mm and week 24: -20 mm; 95% CI, -16 to -22 mm). Similarly, significant decreases were noted in the CRP level (week 12: -0.51 mg/dL; 95% CI, -0.47 to -0.56 mg/dL and week 24: -1.16 mg/dL; 95% CI, -1.03 to -1.30 mg/dL) and ESR (week 12: -11 mm/h; 95% CI, -10 to 12 mm/h and week 24: -25 mm/h; 95% CI, -12 to -26 mm/h) (all P < .001). Conclusions and Relevance: The findings of this study suggest that improvements in clinical outcomes among participants randomized to placebo were not limited to subjective outcomes. Even if these findings could largely demonstrate a regression to the mean, they should be considered for future trial design, as unexpected favorable placebo responses may result in a well-designed trial becoming underpowered to detect the treatment difference needed in clinical drug development.


Assuntos
Artrite Reumatoide , Sedimentação Sanguínea , Proteína C-Reativa/análise , Avaliação de Resultados em Cuidados de Saúde , Medição da Dor/métodos , Efeito Placebo , Artrite Reumatoide/sangue , Artrite Reumatoide/psicologia , Artrite Reumatoide/terapia , Autoavaliação Diagnóstica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente
4.
J Headache Pain ; 21(1): 117, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977761

RESUMO

BACKGROUND AND AIM: Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. METHODS: The working group identified relevant questions and agreed upon recommendations. Because no data were required to answer the questions, the GRADE approach was not applicable, and thus only expert opinion was provided according to an amended Delphi method. The initial 12 topics for discussion were revised in the opinion of the majority of the panelists, and after a total of 6 rounds of negotiations, the final agreement is presented. RESULTS/RECOMMENDATIONS: Two primary and mechanism-based recommendations are provided for the results of clinical trials: [1] to distinguish the placebo or nocebo response from the placebo or nocebo effect; and [2] for any favorable outcome observed after placebo administration, the term "placebo response" should be used, and for any unfavorable outcome recorded after placebo administration, the term "nocebo response" should be used (12 out of 17 panelists agreed, 70.6% agreement). The placebo or nocebo responses are attributed to a set of factors including those that are related to the medical condition (e.g. natural history, random comorbidities, etc.), along with idiosyncratic ones, in which the placebo or nocebo effects are attributed to idiosyncratic, or nonspecific mechanisms, exclusively (e.g. expectation, conditioning, observational learning etc.). To help investigators and practitioners, the panel summarized a list of environmental factors and idiosyncratic dynamics modulating placebo and nocebo effects. Some of them are modifiable, and investigators or physicians need to know about them in order to modify these factors appropriately to improve treatment. One secondary recommendation addresses the use of the terms "placebo" and "nocebo" ("placebos" and "nocebos" in plural), which refer to the triggers of the placebo/nocebo effects or responses, respectively, and which are inert agents or interventions that should not be confused with the placebo/nocebo responses or effects themselves (all panelists agreed, 100% agreement). CONCLUSION: The working group recommends distinguishing the term response from effect to describe health changes from before to after placebo application and to distinguish the terms placebo(s) or nocebo(s) from the health consequences that they cause (placebo/nocebo responses or effects).


Assuntos
Efeito Nocebo , Efeito Placebo , Cefaleia , Humanos
5.
PLoS One ; 15(8): e0236592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790792

RESUMO

Caffeine improves cycling time trial performance through enhanced motor output and muscle recruitment. However, it is unknown if caffeine further increases power output entropy. To investigate the effects of caffeine effects on cycling time trial performance and motor output entropy (MOEn), nine cyclists (VO2MAX of 55 ± 6.1 mL.kg.-1min-1) performed a 4 km cycling time trial (TT4km) after caffeine and placebo ingestion in a counterbalanced order. Power output data were sampled at a 2 Hz frequency, thereafter entropy was estimated on a sliding-window fashion to generate a power output time series. A number of mixed models compared performance and motor output entropy between caffeine and placebo every 25% of the total TT4km distance. Caffeine ingestion improved power output by 8% (p = 0.003) and increased MOEn by 7% (p = 0.018). Cyclists adopted a U-shaped pacing strategy after caffeine ingestion. MOEn mirrored power output responses as an inverted U-shape MOEn during the time trial. Accordingly, a strong inverse correlation was observed between MOEn and power output responses over the last 25% of the TT4km (p < 0.001), regardless of the ingestion, likely reflecting the end spurt during this period (p = 0.016). Caffeine ingestion improved TT4km performance and motor output responses likely due to a greater power output entropy.


Assuntos
Desempenho Atlético , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Resistência Física/efeitos dos fármacos , Adulto , Ciclismo , Entropia , Humanos , Masculino , Efeito Placebo
6.
PLoS One ; 15(8): e0237491, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841256

RESUMO

PURPOSE: Viral upper respiratory infections are associated with significant health and economic impact. This study sought to determine the efficacy of routine immune system micronutrient supplementation on the incidence, duration and severity of common cold symptoms. METHODS: This pilot study was a randomized, double-blinded, placebo-controlled trial of N = 259 with asymptomatic participants aged 18 to 65 in two cold seasons of 2016 and 2017. The treatment group received an immune system targeted micronutrient caplet, while the placebo group received a micronized cellulose caplet externally identical to the treatment caplet. Weekly surveys were sent electronically to participants to document common cold incidence, duration and severity. Primary statistical results were obtained using mixed-effects logistic regressions to account for longitudinal measurements for participants. RESULTS: The odds of acquiring an upper respiratory infection, adjusted for potential confounders, was estimated to be 0.74 times lower in the treatment group (p = 0.14). The odds of reporting specific symptoms were statistically lower in the treatment arm compared to the placebo arm for runny nose (OR = 0.53, p = 0.01) and cough (OR = 0.51, p = 0.04). Shorter durations of runny nose and cough were also observed in the treatment arm compared to placebo (both p < 0.05). There was no significant difference in severity of symptoms in either group. The observed proportion of reported cold symptoms in the treatment group was lower compared to the placebo group between late January and February in two consecutive cold seasons. Given the physical, workplace and economic impact of upper respiratory infections, this low cost and low risk intervention should be further studied with more robust investigation and meticulous experimental design.


Assuntos
Resfriado Comum/tratamento farmacológico , Micronutrientes/uso terapêutico , Adolescente , Adulto , Idoso , Resfriado Comum/complicações , Resfriado Comum/epidemiologia , Resfriado Comum/patologia , Tosse/patologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Faringite/patologia , Projetos Piloto , Efeito Placebo , Índice de Gravidade de Doença , Adulto Jovem
7.
J Med Chem ; 63(21): 12137-12155, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32804502

RESUMO

This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims lacks a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other "natural" panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the "natural" label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.


Assuntos
Canabidiol/farmacologia , Animais , Canabidiol/farmacocinética , Canabidiol/uso terapêutico , Canabidiol/toxicidade , Química Farmacêutica , Ensaios Clínicos como Assunto , Humanos , Efeito Placebo
8.
BMJ ; 370: m1668, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690477

RESUMO

Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights "predictive coding" and "bayesian brain" as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.


Assuntos
Dor Crônica/tratamento farmacológico , Relações Médico-Paciente/ética , Placebos/efeitos adversos , Padrões de Prática Médica/ética , Teorema de Bayes , Dor Crônica/psicologia , Decepção , Método Duplo-Cego , Ética Médica , Humanos , Efeito Placebo , Placebos/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos
9.
Cochrane Database Syst Rev ; 7: CD012129, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32702783

RESUMO

BACKGROUND: Perineal trauma, due to spontaneous tears, surgical incision (episiotomy), or in association with operative vaginal birth, is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain, and its effectiveness and safety should be assessed. This is an update of the review, last published in 2017. OBJECTIVES: To determine the effects of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register (4 October 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (4 October 2019) and screened reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol or acetaminophen, for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs, but none were identified. We excluded quasi-RCTs and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The certainty of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. MAIN RESULTS: We included 17 RCTs, 16 of which randomised 1132 women to aspirin or placebo; one RCT did not report numbers of women. Two RCTs (of 16) did not contribute data to meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear, due to poor reporting. We included four comparisons: aspirin versus placebo (15 RCTs); 300 mg versus 600 mg aspirin (1 RCT); 600 mg versus 1200 mg aspirin (2 RCTs); and 300 mg versus 1200 mg aspirin (1 RCT). Aspirin versus placebo Aspirin may result in more women reporting adequate pain relief four to eight hours after administration compared with placebo (risk ratio (RR) 2.03, 95% confidence interval (CI) 1.69 to 2.42; 13 RCTs, 1001 women; low-certainty evidence). It is uncertain whether aspirin compared with placebo has an effect on the need for additional pain relief (RR 0.25, 95% CI 0.17 to 0.37; 10 RCTs, 744 women; very low-certainty evidence), or maternal adverse effects (RR 1.08, 95% CI 0.57 to 2.06; 14 RCTs, 1067 women; very low-certainty evidence), four to eight hours after administration. Analyses based on dose did not reveal any clear subgroup differences. 300 mg versus 600 mg aspirin It is uncertain whether over four hours after administration, 300 mg compared with 600 mg aspirin has an effect on adequate pain relief (RR 0.82, 95% CI 0.36 to 1.86; 1 RCT, 81 women) or the need for additional pain relief (RR 0.68, 95% CI 0.12 to 3.88; 1 RCT, 81 women). There were no maternal adverse effects in either aspirin group. 600 mg versus 1200 mg aspirin It is uncertain whether over four to eight hours after administration, 600 mg compared with 1200 mg aspirin has an effect on adequate pain relief (RR 0.85, 95% CI 0.52 to 1.39; 2 RCTs, 121 women), the need for additional pain relief (RR 1.32, 95% CI 0.30 to 5.68; 2 RCTs, 121 women), or maternal adverse effects (RR 3.00, 95% CI 0.13 to 69.52; 2 RCTs, 121 women). 300 mg versus 1200 mg aspirin It is uncertain whether over four hours after administration, 300 mg compared with 1200 mg aspirin has an effect on adequate pain relief (RR 0.62, 95% CI 0.29 to 1.32; 1 RCT, 80 women) or need for additional pain relief (RR 2.00, 95% CI 0.19 to 21.18; 1 RCT, 80 women). There were no maternal adverse effects in either aspirin group. None of the included RCTs reported on neonatal adverse effects. No RCTs reported on secondary review outcomes of: prolonged hospitalisation due to perineal pain; re-hospitalisation due to perineal pain; fully breastfeeding at discharge; mixed feeding at discharge; fully breastfeeding at six weeks; mixed feeding at six weeks; perineal pain at six weeks; maternal views; or maternal postpartum depression. AUTHORS' CONCLUSIONS: Single dose aspirin may increase adequate pain relief in women with perineal pain post-episiotomy compared with placebo. It is uncertain whether aspirin has an effect on the need for additional analgesia, or on maternal adverse effects, compared with placebo. We downgraded the certainty of the evidence because of study limitations (risk of bias), imprecision, and publication bias. Aspirin may be considered for use in non-breastfeeding women with post-episiotomy perineal pain. Included RCTs excluded breastfeeding women, so there was no evidence to assess the effects of aspirin on neonatal adverse effects or breastfeeding. Future RCTs should be designed to ensure low risk of bias, and address gaps in the evidence, such as the secondary outcomes established for this review. Current research has focused on women with post-episiotomy pain; future RCTs could be extended to include women with perineal pain associated with spontaneous tears or operative birth.


Assuntos
Dor Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Complicações do Trabalho de Parto/tratamento farmacológico , Períneo , Episiotomia/efeitos adversos , Feminino , Humanos , Dor Pós-Operatória/tratamento farmacológico , Efeito Placebo , Período Pós-Parto , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
11.
Pain ; 161(8): 1939-1940, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32701853

Assuntos
Efeito Placebo
12.
Nervenarzt ; 91(8): 675-683, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32607602

RESUMO

BACKGROUND: There is substantial evidence that placebo and nocebo effects occur during treatment with antidepressants. A better understanding of the underlying mechanisms of these effects is necessary to optimize the outcome of treatment and to make clinical studies more sensitive. METHODS: Placebo and nocebo mechanisms were analyzed based on empirical studies and the results are summarized in a narrative review. RESULTS: Clinical studies and also experimental mechanism-oriented studies underline the effects of placebo and nocebo mechanisms in the treatment with antidepressants. CONCLUSION: The success of treatment in the use of antidepressants can be increased and the probability of side effects can be reduced by the effective use of placebo mechanisms and reduction of nocebo effects. The results emphasize the influence of clinician-patient interactions, the role of the treatment context and previous experiences with other treatments of the patient. Simultaneously, the results of this research field stimulate a new understanding of mental disorders, in particular depression and also provide points of reference for optimization of psychotherapeutic treatment.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Efeito Nocebo , Efeito Placebo , Antidepressivos/efeitos adversos , Humanos
13.
Nervenarzt ; 91(8): 684-690, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32617632

RESUMO

Reflecting on results of recent placebo research, this article analyzes relevant key concepts and ethical positions. "Placeboids" and possibly open-label placebo treatments should replace any deceptive use of sham medication. Their use should give rise to a critical consideration of the modern patient-physician relationship.


Assuntos
Efeito Placebo , Decepção , Ética Médica , Humanos , Princípios Morais , Relações Médico-Paciente
14.
Nervenarzt ; 91(8): 700-707, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32642945

RESUMO

In the past few decades, research on pain and placebo analgesia has gained importance both scientifically and clinically. In this article, the current findings and focus of research as well as the significance of placebo research for assessing the effectiveness of pain medication are illustrated. The underlying mechanisms of placebo analgesia not only have implications for theoretical models but also offer clinically relevant guidelines for everyday interventions in pain treatment. However, many placebo phenomena are not fully understood and have to be investigated further in order to exploit the full potential of placebo effects. Interindividual differences and their inclusion in treatment will play a major role in this aspect.


Assuntos
Analgesia , Efeito Placebo , Humanos , Dor/tratamento farmacológico , Manejo da Dor
15.
Nervenarzt ; 91(8): 667-674, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32642946

RESUMO

The learned placebo response of the immune system is based on the mutual interaction between the brain and the immune system; both systems continually exchange information via humoral and neural communication pathways. This communication network enables the modification, i.e. suppression or stimulation, of peripheral immune functions by classical or Pavlov's conditioning. The present article provides an overview of the results of recent experimental animal studies, which also document the potential clinical relevance of learned immune responses. Learned immunological responses mediated by classical conditioning have also been demonstrated in humans. The knowledge gained from experimental data and clinical observations paves the way for a potential implementation of learned immune responses as supportive measures to standard immunopharmacological treatment strategies to reduce drug dosage as well as adverse side effects while simultaneously maximizing the therapeutic effect.


Assuntos
Sistema Imunitário , Aprendizagem , Efeito Placebo , Animais , Encéfalo , Condicionamento Clássico , Humanos
16.
Sci Rep ; 10(1): 12181, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699231

RESUMO

Adapting one's attitudes and behaviors to group norms is essential for successful social interaction and, thus, participation in society. Yet, despite its importance for societal and individual functioning, the underlying neuropharmacology is poorly understood. We therefore investigated its neurochemical and neural correlates in a pharmacological functional magnetic resonance imaging study. Lysergic acid diethylamide (LSD) has been shown to alter social processing and therefore provides the unique opportunity to investigate the role of the 5-HT2A receptor in social influence processing. Twenty-four healthy human volunteers received either (1) placebo + placebo, (2) placebo + LSD (100 µg), or (3) the 5-HT2A receptor antagonist ketanserin (40 mg) + LSD (100 µg) at three different occasions in a double-blind, randomized, counterbalanced, cross-over design. LSD increases social adaptation but only if the opinions of others are similar to the individual's own. These increases were associated with increased activity in the medial prefrontal cortex while participants received social feedback. Furthermore, pretreatment with the 5-HT2A antagonist ketanserin fully blocked LSD-induced changes during feedback processing, indicating a key role of the 5-HT2A system in social feedback processing. Our results highlight the crucial role of the 5-HT-system in social influence and, thus, provide important insight into the neuropharmacological basis of social cognition and behavior.


Assuntos
Dietilamida do Ácido Lisérgico/farmacologia , Receptores de Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologia , Normas Sociais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Ketanserina/administração & dosagem , Ketanserina/farmacologia , Dietilamida do Ácido Lisérgico/administração & dosagem , Imagem por Ressonância Magnética , Masculino , Personalidade/efeitos dos fármacos , Efeito Placebo , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/administração & dosagem , Adulto Jovem
17.
Nervenarzt ; 91(8): 708-713, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32691079

RESUMO

The efficacy of placebo effects is proven in experimental, clinical and meta-analytical studies. However, harnessing placebo effects in clinical treatment contexts is hampered legally and ethically, since it has been considered necessary to conceal the inert nature of a placebo application. Interestingly, the results of recently published small, randomized trials suggest that patients can experience symptom relief after taking pills that they know lack any medication. In particular, these so-called open-label placebos (OLP) improved strongly fluctuating and individually distressing complaints such as gastrointestinal, neurological, psychosomatic and pain symptoms. Although the mechanisms are largely unknown, the open-label placebo application might be a promising way of fostering placebo effects in clinical settings. Initial study protocols already provide schedules for OLP use as an additional treatment in opioid use disorders. Likewise, the reduction of side effects, conversion effects or withdrawal symptoms through OLP applications in pharmacologically active treatments appear to serve as appropriate therapy goals. Further mechanistic studies are urgently needed to investigate the thus far only hypothetically proposed underlying mechanisms of OLP.


Assuntos
Efeito Placebo , Projetos de Pesquisa , Humanos , Dor/tratamento farmacológico , Dor/prevenção & controle
18.
Sci Rep ; 10(1): 12130, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699287

RESUMO

The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20-59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2'-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.


Assuntos
Apoptose , Hidrogênio/química , Leucócitos Mononucleares/metabolismo , Água/administração & dosagem , Adulto , Antioxidantes/análise , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Análise por Conglomerados , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Humanos , Hidrogênio/administração & dosagem , Hidrogênio/farmacologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Efeito Placebo , Transcriptoma , Água/química , Adulto Jovem
19.
Updates Surg ; 72(4): 1125-1133, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32666477

RESUMO

BACKGROUND: Although bariatric surgery (BS) predisposes patients to development of gallstone formation, a preventive strategy is still in debate. AIM: To compare the incidence of gallstone formation between patients treated with ursodeoxycholic acid (UDCA) vs. placebo for a duration of 6 months following BS. METHODS: This multicenter randomized, double-blind controlled trial entails treatment with UDCA vs. an identical-looking placebo. The primary outcome was gallstone formation, as measured by abdominal ultrasound. RESULTS: The data of 209 subjects were enrolled in the study, and 92 subjects completed the study and were analyzed (n = 46 for each study group). The high dropout rate was mainly due to difficulties in adding more medications and swallowing the pill. Among the subjects who completed the study, 77.2% were women, and their mean age and pre-surgery BMI were 42.2 ± 10.2 years and 44.4 ± 6.1 kg/m2, respectively. Gallstone formation was recorded in 45.7% (n = 21) vs. 23.9% (n = 11) of subjects among placebo vs. UDCA groups, respectively, p = 0.029. Subgroup-analysis, according to surgery type, found that the results were significant only for SG subjects (p = 0.041), although the same trend was observed for OAGB/RYGB. Excess Weight Loss percent (%EWL) at 6 months post-surgery was 66.0 ± 17.1% vs. 71.8 ± 19.5% for the placebo and UDCA groups, respectively; p = 0.136. A trend towards a reduction in prescribed comorbidity medications was noted within-groups during the follow-up period, as compared to baseline, with no between-group differences (p ≥ 0.246). Moreover, no between-group differences were found for blood test results (p ≥ 0.063 for all). CONCLUSION: Administration of UDCA significantly decreased gallstone formation at 6 months at following BS. CLINICALTRIALS. GOV NUMBER: NCT02319629.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Cálculos Biliares/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Ácido Ursodesoxicólico/administração & dosagem , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Cálculos Biliares/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Efeito Placebo , Complicações Pós-Operatórias/etiologia , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA