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. 2025 Jul;31(7):2186-2195.
doi: 10.1038/s41591-025-03685-9. Epub 2025 Jun 3.

An international Delphi consensus for reporting of setting in psychedelic clinical trials

Chloé Pronovost-Morgan  1   2   3 , Kyle T Greenway  4   5   6 , Leor Roseman  7   8 ; ReSPCT Experts
Collaborators, Affiliations

An international Delphi consensus for reporting of setting in psychedelic clinical trials

Chloé Pronovost-Morgan et al. Nat Med. 2025 Jul.

Abstract

Psychedelic substances exhibit complex interactions with the 'set and setting' of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables' known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based guidelines for reporting settings in psychedelic clinical research, according to an international group of psychedelic researchers, clinicians and past trial participants. We conducted a Delphi consensus study composed of four iterative rounds of quasi-anonymous online surveys. A total of 89 experts from 17 countries independently listed potentially important psychedelic setting variables. There were 770 responses, synthesized into 49 distinct items that were subsequently rated, debated and refined. The process yielded 30 extra-pharmacological variables reaching predefined consensus ratings:i.e., 'important' or 'very important' for ≥70% of experts. These items compose the Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines, categorized into physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. Emergent findings reveal significant ambiguities in current conceptualizations of set and setting. The ReSPCT guidelines and accompanying explanatory document provide a new standard for the design and documentation of extra-pharmacological variables in psychedelic clinical research.

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Conflict of interest statement

Competing interests: The study authors declare the following competing interests: M.A. is a paid consultant for Compass Pathways, providing training and mentorship to clinical trial therapists. He receives financial compensation for teaching at organizations including the OPEN Foundation, the Integrative Psychiatry Institute and the Michener Institute, and is also financially compensated for professional services provided to ICEERS. S.A. has received research support from Monash for work as a clinical trial therapist and from MAPS/Lykos for work as a principal investigator and clinical trial therapist. F.S.B. is a scientific advisor for MindState Design Labs, LLC and WavePaths, Ltd., and has consulted with Gilgamesh Pharmaceuticals and Eli Lilly. A.B. has received financial compensation from Cybin, Inc., as a consultant and in his former role as Cybin’s Chief Clinical Officer, and has filed patents on the use of psychedelic compounds for psychiatric indications. C.C. is the CEO of Biocase, a biopharmaceutical company in Brazil developing a naturalistic psilocybin formulation from dried mushrooms. A.K.D. is a board member at Source Research Foundation. N.D. holds a position in the Regulation (POPLAR) initiative at the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard Law School and is a board member of Psymposia, a 501(c)(3) research nonprofit organization focused on psychedelic science and harm reduction. Outside the submitted work, N.D. has received personal fees from Psymposia, the Ethical Legal Implications of Psychedelics in Society (ELIPSIS) Program at Baylor College of Medicine, the Center for Psychedelic Drug Research and Education at The Ohio State University, the University of Wisconsin-Madison and Bentley University’s Jeanne and Dan Valente Center for Arts & Sciences. D.E. is a paid advisor for Aya Biosciences, Lophora Aps, Clerkenwell Health and MindState Design Lab. H.F. is a trainer for the nonprofit organization TheraPsil and was a volunteer member of its training and ethics committees. He was the Montreal site physician for MAPPUSX, a phase 3 clinical trial of MDMA-assisted therapy for PTSD sponsored by MAPS. He is the founder of Mystic Health and an investor in Beckley Psytech. F.M. is the site principal investigator for the clinical trial ‘Efficacy, Safety, and Tolerability of COMP360 in Participants with Treatment-Resistant Depression’ by COMPASS Pathways and ‘RE-104 Safety and Efficacy Study in Postpartum Depression’ by Reunion Neuroscience. T.N. was the part-time scholar-in-residence at Tactogen Public Benefit Corporation until May 2024, working on projects related to justice, accessibility and expanded definitions of psychedelic clinical trials. D.P. is employed by and holds equity in Neurala Biosciences. K.H.P. is an employee of Boehringer Ingelheim GmBH & CO KG, the chief scientist and a board member of the Heffter Research Institute, and a scientific advisor for the MIND Foundation. S. Reed receives honoraria for speaking engagements and consultations related to psychedelic therapy. She was an inaugural board member of the Board of Psychedelic Medicines and Therapies (USA), which develops certification standards for psychedelic-assisted therapists. She currently lectures internationally on culturally responsive practices in psychedelic therapy with Mind Medicine Australia, the Psychedelic Liberation Training and Vital (Psychedelics Today). D.R. is an honorary board member of the nonprofit organization MAPS Deutschland. His institution (Charité) has received research funding from Beckley Psytech, COMPASS Pathways and MAPS Europe for psychedelic medicines research. L.R. is the founder of Ripples, a nonprofit peacebuilding organization. W.R. owns stock in COMPASS Pathways and Sunstone Therapies. J. Rucker has been awarded grant funding (received and managed by King’s College London) from COMPASS Pathways, Beckley PsyTech, the Multidisciplinary Association for Psychedelic Studies (MAPS), the National Institute for Health Research (NIHR), Wellcome Trust and the Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust. S. Ruffell is the cofounder of Onaya Science, a not-for-profit research organization, and the CEO of Onaya, an organization that delivers psychedelic mentorship training courses. He is also the chief medical officer of MINDS, a not-for-profit research organization. K.T. works with Lykos as a therapist and educator. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flow diagram for study participants and items.
Diagram showing the Delphi study flow, from recruitment to the final round. The diagram includes the number of participating experts per round, and the item’s progression from inception to being accepted, debated, improved or rejected.
Fig. 2
Fig. 2. Expert responses regarding the separability and conceptual overlap of set and setting factors, and temporal span of setting in psychedelic clinical trials.
a, Experts rated their level of agreement with the statement ‘set and setting can be studied separately’ on a 5-point Likert scale. b, Experts rated the conceptual overlap between set and setting on a scale from 0 (no overlap) to 100 (complete overlap). c, Experts indicated the span of setting in the context of a clinical trial according to the following options: from the start to the end of the dosing session, throughout the treatment phase (preparation, dosing and integration), from recruitment to follow-up or other.
See this image and copyright information in PMC

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