Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols.
Damian Swieczkowski, Aleksander Kwaśny, Krzysztof Sadko, Wiesław Jerzy Cubała
European Neuropsychopharmacology January 16, 2026 DOI: 10.1016/j.euroneuro.2025.112746 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 13 |
| Population | Clinical trial protocols for psilocybin studies targeting major depressive disorder or treatment-resistant depression |
| Topics | Psilocybin |
| Keywords | Respct guidelines Set and setting |
| Citations | 1 |
| Key findings | Only 15.6% of ReSPCT checklist items were fully reported across 13 psilocybin clinical trial protocols, with procedural elements well covered but contextual and equity-related domains—such as cultural competence, objects or decorations, and access to nature—largely absent. |
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.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| Blinding and expectancy confounds in psychedelic randomized controlled trials | 2021 | Systematic review | |
| Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials | 2016 | Systematic review | |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies | 2022 | Systematic review |
Citations in the library
Cites 25
- The hidden therapist: evidence for a central role of music in psychedelic therapy Psychopharmacology February 1, 2018
- Psychedelic-Assisted Psychotherapy—A Systematic Review of Associated Psychological Interventions Frontiers in Psychology June 10, 2022
- Psilocybin-assisted therapy for depression: A systematic review and meta-analysis. Psychiatry Research November 1, 2023
- Psychedelics and Psychotherapy: Cognitive-Behavioral Approaches as Default Frontiers in Psychology May 23, 2022
- Effects of Setting on Psychedelic Experiences, Therapies, and Outcomes: A Rapid Scoping Review of the Literature Current Topics in Behavioral Neurosciences 2022
and 20 more in the library