Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology – January 16, 2026
Source: PubMed
Summary
Psilocybin trials for Major Depressive Disorder and Treatment-Resistant Depression often overlook critical contextual details. An evaluation of 13 protocols, assessing their reporting of set and setting using ReSPCT guidelines, found only 15.6% of 390 items fully compliant. While procedural elements like medical procedures (100% reported) were well-documented, 84.6% of protocols lacked cultural competence information, and 92.3% omitted details on the therapeutic environment. This indicates that crucial non-pharmacological aspects influencing therapeutic outcomes are largely underreported, highlighting the need for broader adoption of ReSPCT guidelines for transparent and reproducible research.
Abstract
Psilocybin-assisted therapies are increasingly studied for Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD), and methodological rigor requires both pharmacological evaluation and consistent reporting of non-pharmacological variables that influence therapeutic outcomes. To address this need, the ReSPCT (Reporting of Setting in Psychedelic Clinical Trials) guidelines were recently introduced, providing a 30-item framework for standardized reporting of set and setting. This study aimed to evaluate how current psilocybin clinical trial protocols incorporate these elements and to identify domains requiring improvement. We systematically searched ClinicalTrials.gov and the EU Clinical Trials Information System (CTIS) for interventional psilocybin studies targeting MDD or TRD, including protocols listing depression as a primary condition. By June 21, 2025, 13 protocols (11 Phase II and 2 Phase III) met the inclusion criteria. Each protocol was assessed using the ReSPCT checklist, yielding a total of 390 item-level assessments rated on a four-point scale. Overall, 61 of 390 entries (15.6%) demonstrated full compliance, 252 (64.6%) partial compliance, and 77 (19.7%) provided no relevant information. Procedural elements, such as medical and experimental procedures (100% compliance), focus and main activities (92.3%), number of sessions (69.2%), and dosing regimens (53.8%), were consistently reported. In contrast, contextual and equity-related domains were markedly underreported: 84.6% of protocols lacked information on cultural competence and safety, 92.3% did not describe objects or decorations, and 84.6% failed to report access to nature. These findings indicate that while procedural safeguards are well documented, critical contextual and equity-relevant aspects remain insufficiently reported. Adopting ReSPCT guidelines may improve transparency and reproducibility.