The Toll-Like Receptor Signalling Pathway Is Altered in iPSC-Derived Cortical Networks From People With Bipolar Disorder.

There has recently been a growing interest in using placebos transparently. Open-label placebos (OLP) are placebos where the patient knows they are receiving a pharmacologically inert treatment. OLP treatments reliably reduce symptoms compared to no treatment [] thanks to at least three important elements: the patient-provider interaction, the act of taking the treatment, and of particular relevance to this paper, the rationale (i.e. the justification for the placebo) []. Previous research has shown that administering OLPs without any rationale provides little to no benefit, suggesting that the rationale is a necessary component of OLP treatments []. Additionally, initial findings suggest OLPs may perform as well as deceptive placebos when administered with a convincing rationale []. However, most OLP studies have used a close variation of the same rationale [] and no studies to date have sought to optimize the rationale by comparing multiple rationales against each other. Therefore, the aim of the current study is to understand how different rationales can impact outcomes. We also address methodological limitations of prior OLP research. This trial will examine how OLPs and OLP rationales impact pain (intensity, interference, catastrophizing) and medication use (including opioids) during an OLP treatment. This study is a 42-day 4-arm superiority randomized controlled trial. A dismantling design will be used to isolate the placebo effect and the effects of the rationale and of the act of taking an OLP. It will be conducted remotely with chronic-pain patients in the U.S. All patients will interact live with the research team once during a baseline video call. Patients will complete the rest of the study remotely. The study has been registered on under the number .