TY - JOUR
T1 - An international Delphi consensus for reporting of setting in psychedelic clinical trials
AU - Pronovost-Morgan, Chloé
AU - Greenway, Kyle T.
AU - Roseman, Leor
AU - Williams, Keith
AU - Wells, Hattie
AU - Tzarfaty, Keren
AU - Timmermann, Christopher
AU - Lévesque, Julien Thibault
AU - Tadwalkar, Sayali
AU - Szigeti, Balázs
AU - Shutte, Thomas
AU - Schneider, Leonie
AU - Sanders, James W.
AU - Ruffell, Simon
AU - Rucker, James
AU - Roullier, Ian
AU - Rochester, Jessica
AU - Risby, Sally
AU - Richards, William
AU - Richards, Brian
AU - Repantis, Dimitris
AU - Reed, Sara
AU - Ramaekers, Johannes G.
AU - Preller, Katrin H.
AU - Perkins, Daniel
AU - Peekeekoot, Gail
AU - Patchett-Marble, Ryan
AU - Palhano-Fontes, Fernanda
AU - Ona, Genís
AU - Oehen, Peter
AU - Noorani, Tehseen
AU - Neitzke-Spruill, Logan
AU - Moreno, Francisco
AU - McAlpine, Rosalind
AU - Mazarrasa, Jerónimo
AU - Marcus, Olivia
AU - Mallon, Orla
AU - MacLean, Katherine
AU - Lucas, Philippe
AU - Lifshitz, Michael
AU - Lehmann, Alexandre
AU - Langlitz, Nicolas
AU - Knowles, Adam
AU - Kettner, Hannes
AU - Holze, Friederike
AU - Hartogsohn, Ido
AU - Hapke, Emma
AU - Guss, Jeffrey
AU - Gukasyan, Natalie
AU - Greer, George
AU - ReSPCT Experts
N1 - Funding Information:
We would like to thank the cofounders of PsyPAN for their assistance in liaising with and recruiting past clinical trial participants for this project, as well as the PsyPAN members who shared their lived-experience expertise and chose to remain anonymous. We would also like to acknowledge the contributions of the following individuals to the Delphi process: F. Meckel, W. Britton, S. Meikle, M. Jabir and T. Hartle. T. Hartle, who recently passed away, was the first Canadian to receive psilocybin for end-of-life distress associated with a terminal cancer diagnosis. He was a strong advocate for psychedelic research and a valued contributor to this study. This Delphi study was supported by funds from the Societal Engagement Seed Fund, Imperial College London, which were used to remunerate past clinical trial participants for their time completing the four survey rounds. L.R. was supported by a fellowship from The Huxley Foundation. J.S.A. was partially supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (T32AR007080-44S1). G.A.-L. received support for this work from the National Institutes of Health (T32DA007250) and R. T. Chubrich. A.K.D. is supported by the Center for Psychedelic Drug Research and Education. N. Gukasyan was supported by the New York State Psychiatric Institute. F.H. was supported by the Swiss National Science Foundation (P500PM_210867). N.L. and D.R were supported by a grant from the German Ministry of Education and Research (01GGP2214D and 01GP2214A, respectively). J. Rucker acknowledges support from a fellowship from the National Institute for Health Research (NIHR; CS-2017-17-007, 2018\u20132023). This study presents independent research partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King\u2019s College London. C.T. is funded by A. Bilton, the Tyringham Initiative and a Varela Award by Mind and Life. No funding was received for the preparation of this paper, and the views presented in this work are independent of those of the various funding sources.
Funding Information:
All participating experts were given the option to contribute as coauthors or be acknowledged in future publications, and former trial participants were additionally remunerated at a rate of \u00A320 per completed survey, based on consultation with PsyPAN. This renumeration was supported with funding from the Imperial College London Societal Engagement Seed Fund, which supports patient and public involvement in research.
Funding Information:
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\u2019s 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\u2019s 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 \u2018Efficacy, Safety, and Tolerability of COMP360 in Participants with Treatment-Resistant Depression\u2019 by COMPASS Pathways and \u2018RE-104 Safety and Efficacy Study in Postpartum Depression\u2019 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 (Charit\u00E9) 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\u2019s 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.
Publisher Copyright:
© The Author(s) 2025.
PY - 2025/7
Y1 - 2025/7
N2 - 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.
AB - 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.
U2 - 10.1038/s41591-025-03685-9
DO - 10.1038/s41591-025-03685-9
M3 - Article
SN - 1078-8956
VL - 31
SP - 2186
EP - 2195
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -