The role of dorsolateral prefrontal cortex on placebo effect of regulating social pain: A TMS study

Under the influence of the novel coronavirus epidemic, some negative social events, such as separation of family or friends and home isolation have increased. These events can cause negative emotion experiences similar to physical pain, thus they are called social pain. Placebo effect refers to the positive response to the inert treatment with no specific therapeutic properties, which has been shown to be one of the effective ways to alleviate social pain. Studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays a key role in placebo effect. Therefore, this study aimed to explore whether activating DLPFC by using transcranial magnetic stimulation (TMS) could improve the ability of placebo effects to regulate social pain. Besides, we also combined neuroimaging and neuromodulation techniques to provide bidirectional evidence for the role of the DLPFC on placebo effects. We recruited a total of 100 participants to finish the task of negative emotional rating of the social exclusion images. Among them, 50 participants were stimulated by TMS at the right DLPFC (rDLPFC), while the others were assigned to the sham group. This study contained two independent variables. The between-subject variable was TMS group (rDLPFC-activated group or sham group) and the within-subject variable was placebo type (no-placebo and placebo). All participants received nasal spray in two blocks. In the no-placebo condition, participants were instructed that they would receive a saline nasal spray which helped to improve physiological readings;in placebo block, participants were told to administrate an intranasal fluoxetine spray (saline nasal spray in fact) that could reduce unpleasantness within 10 minutes. To strengthen the expectation of intranasal fluoxetine, participants viewed a professional introduction to fluoxetine's clinical and academic usage including downregulating negative emotion, such as fear, anxiety, and disgust. Participants who received the placebo block first would be reminded that fluoxetine's effect was over before the next block to reduce the carry-over for the following block. Self-reported negative emotional and electroencephalogram data were recorded. There was a significant two-way interaction of TMS group and placebo type. Results showed that compared with the sham group, participants in the rDLPFC-activated group reported less negative emotional feeling and had a lower amplitude of the late positive potential (LPP) in placebo condition, a component that reflects the emotional intensity, suggesting that activating rDLPFC can improve the ability of placebo effect to regulate social pain. The above finding suggested that activating DLPFC can improve the placebo effect of regulating negative emotion. Moreover, this study is the first attempt to investigate the enhancement of placebo effects by using TMS on emotion regulation. The findings not only support the critical role of DLPFC on placebo effect using neuroimaging and neuromodulation techniques, but also provide a potential brain target for treating emotional regulation deficits in patients with psychiatric disorders. © 2023 WANG Mei.

Is There a Moral Issue When Doctors Prescribe Placebos?

Medicine has made use of placebos, or sugar pills, with no medicinal value for several thousand years. Even clinical studies conducted today use placebos to compare the efficacy of investigative medications or treatments. For example, in the COVID-19 era, experimental investigations including hydroxychloroquine, steroids, or plasma from patients who have had COVID-19 and have antibodies that may be efficacious in treating COVID-19, have been compared with placebo or inert substances that certainly don't affect the course of the disease. Only in this fashion is it possible to determine the response to these and other substances. The use of placebos has raised an ethical question regarding giving patients an inert substance which has no known impact on the disease or condition being studied. Doctors or other medical investigators have a moral obligation to inform patients that they may be receiving either an active drug or a placebo. The patient cannot be told, however, which arm of a study they are in and whether they received the active drug or the placebo until the study has been completed. This article explains how placebos work and offers advice on the clinical use of placebos.

NIH Recommends Against Ivermectin

On Apr 29, the NIH recommended against use of the antiparasitic drug ivermectin for treatment of COVID-19 outside of a clinical trial. The recommendation was made because recent randomized, placebo-controlled trials of ivermectin have produced negative results and because alternative drugs that have been shown to be effective for treatment of COVID-19 are available. Ivermectin has been used for years for treatment of infections caused by parasitic organisms such as Strongyloides stercoralis and Onchocerca volvulus. In a randomized, double-blind trial, 1358 outpatient adults with COVID-19 and at least one risk factor for disease progression whose symptoms had begun seven days and above previously received ivermectin 400 mcg/kg or placebo once daily for 3 days.

Influence on study outcomes of an inpatient study by the behavior of the study staff (PINgPOng): study protocol for a randomized clinical trial.

BACKGROUND: The placebo effect as the symptom improvement following inert treatments is a fixed component of RCTs to differentiate between specific effects of the tested pharmacological substance from other unspecific effects. The PINgPOng study was set up to analyze the influence of a study team trained to either minimize the placebo response and optimize drug-placebo differences or to maximize the placebo response to increase drug efficacy by unspecific factors on the study results of a RCT in a classical early clinical trial setting. METHODS/DESIGN: PINgPOng is a single-center, prospective, randomized, double-blind, placebo-controlled study in a 3-group, 2-sequence, 2-period cross-over design. The study is conducted according to the principles of ICH-GCP and the Declaration of Helsinki on the Phase I-Unit of the University Hospital Bonn. The primary endpoint is the pain intensity in the cold pressor test before and after the administration of 15 mg oxycodone or placebo. The pain intensity is compared between three study conditions: 32 healthy volunteers in each study arm will be treated either by an untrained study team (arm A), by a study team trained to maximize (arm B), or to minimize placebo responses (arm C). Neuroendocrine factors (alpha-amylase activity, salivary cortisol), characteristic traits (anxiety, depression, stress), and somatic reactions are analyzed as covariates of the pain perception. DISCUSSION: The PINgPOng study will allow to answer the question whether and to what extent the behavior of a trained study team (neutral vs. maximize vs. minimize placebo responses) will differentially affect placebo responses in a setting of a highly standardized early clinical trial. The results will help to control the placebo effects by education of the clinical study team and to avoid unnecessary high placebo effects in clinical development. TRIAL REGISTRATION: German Clinical Trials Register DRKS00013586 . Registered on December 22, 2017.

Why we heal: The evolution of psychological healing and implications for global mental health.

Why do humans heal one another? Evolutionary psychology has advanced our understanding of why humans suffer psychological distress and mental illness. However, to date, the evolutionary origins of what drives humans to alleviate the suffering of others has received limited attention. Therefore, we draw upon evolutionary theory to assess why humans psychologically support one another, focusing on the interpersonal regulation of emotions that shapes how humans heal and console one another when in psychosocial distress. To understand why we engage in psychological healing, we review the evolution of cooperation among social species and the roles of emotional contagion, empathy, and self-regulation. We discuss key aspects of human biocultural evolution that have contributed to healing behaviors: symbolic logic including language, complex social networks, and the long period of childhood that necessitates identifying and responding to others in distress. However, both biological and cultural evolution also have led to social context when empathy and consoling are impeded. Ultimately, by understanding the evolutionary processes shaping why humans psychologically do or do not heal one another, we can improve our current approaches in global mental health and uncover new opportunities to improve the treatment of mental illness across cultures and context around the world.