Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols.

Psilocybin-assisted therapies are being tested for major depressive disorder and treatment-resistant depression, but rigorous research requires not only measuring the drug's effects but also consistently reporting non-pharmacological factors—such as the physical and social environment (set and setting)—that can influence outcomes. To address this, the ReSPCT guidelines were developed as a 30-item framework for standardized reporting. This review evaluated 13 clinical trial protocols (11 Phase II and 2 Phase III) from ClinicalTrials.gov and the EU Clinical Trials Information System. Using the ReSPCT checklist, only 15.6% of 390 item-level assessments showed full compliance; 64.6% had partial compliance, and 19.

Study at a glance

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.