Authors
Yvan Beaussant, Elise Tarbi, Kabir Nigam, Skye Miner, Zachary Sager, Justin Sanders, Michael Ljuslin, Benjamin Gu ́erin, Roxanne Sholevar, Kimberly Roddy, James A. Tulsky, Manish Agrawa
Originally published in General Hospital Psychiatry as Set and setting in psilocybin-assisted therapy: A qualitative study of patients with cancer and depression
Published Date: November – December 2025
Abstract
Background
Psilocybin-assisted therapy (PAT) shows promise for cancer-related depression, yet little research has examined how therapeutic context shapes patient experiences. While set (mindset) and setting (environment) are considered central to psychedelic treatment, empirical evidence on their role in PAT acceptability remains limited. This study explores factors influencing the acceptability of PAT from the perspective of patients with cancer and depression.
Methods
We conducted semi-structured interviews with participants in a clinical trial of psilocybin-assisted therapy. Using template analysis, we examined themes related to the acceptability of the experience and the surrounding therapeutic environment.
Results
Participants (n = 28) described the psilocybin experience as intense and demanding, with therapeutic benefits closely tied to their ability to “surrender”—a term used to describe accepting and remaining open to the experience’s intensity and unpredictability. A safe, supportive, and ethical environment was critical in fostering trust and engagement. Preparation and integration were key to maximizing benefit. Music played a significant but variable role, sometimes enhancing and other times distracting. While the clinical setting provided safety, ceremonial elements added meaning for many.
Conclusions
Findings highlight how therapeutic structure, preparation, and setting shape PAT acceptability, supporting the need for patient-centered approaches to optimize care and outcomes.
Keywords
Cancer; Psilocybin; Psilocybin-assisted therapy; Major depressive disorder; Existential distress
Introduction
The resurgence of interest in psychedelic-assisted therapy (PAT) has renewed attention to the non-pharmacological elements that accompany psychedelic drug administration, such as therapeutic preparation, therapist support, music, and integration practices. These components are widely acknowledged as essential for ensuring participant safety, and growing evidence suggests they may also serve as active contributors to treatment efficacy by shaping patient experiences and facilitating emotional processing [[1], [2], [3], [4], [5]].
This dual role—as both protective and transformative—reflects one of the most significant insights from early psychedelic research: that outcomes are shaped not only by the pharmacological properties of psychedelics, but also by the the quality of the subjective experiences they evoke [[6], [7], [8]]. The concepts of “set” (the individual’s internal mindset) and “setting” (the external environment) have long been recognized as critical this experiential dimension [9]. Rather than viewing these as ancillary factors, contemporary research emphasizes their centrality, highlighting how drug effects are modulated by psychological, relational, and environmental context [[10], [11], [12]].
Despite their theoretical significance, empirical studies that explore how set, setting, and therapeutic context affect the acceptability and efficacy of PAT remain limited. While there is a growing body of quantitative work examining predictors of mystical-type or challenging experiences (e.g., trait absorption, surrender, clear intention) [[13], [14], [15]], fewer studies have qualitatively examined how these elements are perceived by patients, or how they are integrated into therapeutic processes. Likewise, integration—the process through which individuals make sense of and incorporate psychedelic experiences—has emerged as a central but understudied domain [12,16,17]. Recent large-scale qualitative studies suggest that integration is highly individualized, often ongoing, and can be influenced by somatic, relational, and communal practices, not just psychotherapy [16].
In a recent phase 2 open-label clinical trial, the feasibility, safety, and efficacy of a novel psilocybin-assisted therapy model were assessed in patients with cancer and major depressive disorder (MDD) [18,19]. In this study, three to four patients at a time received simultaneous administration of psilocybin, with both individual and group sessions incorporated into the preparation and integration phases of the therapy. The trial found that 80 % of participants reported a sustained reduction in depressive symptoms, and 50 % achieved remission, with no psilocybin-related serious adverse events reported. An initial qualitative analysis of patient experiences in this study focused specifically on the acceptability of this group-therapy treatment model [20]. It suggested that the group approach, in addition to being acceptable, fostered a sense of belonging and connection, deepened meaning, and supported self-transcendence through shared psilocybin experience and group integration.
The present manuscript reports a secondary analysis of the same qualitative dataset, focusing instead on how set, setting, and other therapeutic elements shaped participants’ experiences and perceptions of psilocybin’s effects. By investigating these factors, this study provides empirical insights into the interplay between the psilocybin experience and its therapeutic context, advancing understanding of how to optimize treatment delivery in PAT.
Section snippets
Study design and participants
We used a qualitative descriptive approach [21,22] to examine data collected from the Acceptability of Psilocybin-Assisted Group Therapy in Patients with Cancer and Depression Study (ACCEPT Study) [20]. The ACCEPT study was designed as a qualitative companion to a parent clinical trial titled “The Safety and Efficacy of Psilocybin in Cancer Patients with Major Depressive Disorder” (NCT04593563) [18]. This parent study was a single-center, phase 2 open-label trial that investigated…
Discussion
This qualitative analysis explored the experiences of individuals with cancer and depression who underwent psilocybin-assisted therapy (PAT), with particular attention to how therapeutic elements—especially set and setting—influenced the acceptability, perceived efficacy, and safety of the intervention. Our findings build a conceptual model for understanding how psilocybin’s intense and often challenging effects are made therapeutically acceptable through the interplay of surrender, structure,…
Conclusion
This study highlights that the acceptability and therapeutic impact of psilocybin-assisted therapy are not solely determined by the pharmacological action of the drug, but by a carefully designed therapeutic container that enables trust, surrender, and meaning-making. The psilocybin experience—often emotionally and existentially intense—was made acceptable and even transformative when embedded in a framework of relational safety, skilled preparation, and thoughtful integration. Our findings…
Declaration of conflicting interests
Manish Agrawal is a fiduciary officer with Sunstone Therapies. Yvan Beaussant reports consulting fees from Reunion Neuroscience USA Inc. Yvan Beaussant received a research grant from Sunstone Therapies to conduct this research. Kimberly Roddy is a fiduciary officer with Sunstone Therapies. The other authors declare no potential conflicts of interest.
Acknowledgments
The authors would like to express deep gratitude to the patients who shared some of their precious time and wisdom participating in this study and acknowledge Heather Honstein, William Richards, Brian Richards, Mark Bates, Nicholas Schor, Norma Stevens, Betsy Jenkins, Candace Oglesby, Bob Kaufman, Celia Leeks, and Kevin McGuire for contributing to the conduct of this study.
References
B.T. Anderson et al. Psychedelic medicine: safety and ethical concerns Lancet Psychiatry(2020)
A.D. Rinaldi et al. Sitting with suffering, sitting with humanity: in the common ground of emerging psychedelic-assisted therapies and palliative care (FR208) J Pain Symptom Manage (2022)
R.L. Carhart-Harris et al. REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Barker EL, ed Pharmacol Rev (2019)
A. MacLeod et al.‘Go with the “wave of music” to dive deep’: exploring perceptions of psychedelic-assisted therapy and the role of music within this practice Arts Psychother (2025)
G.M. Goodwin et al. Psychological support for psilocybin treatment: reply to letters on our commentary AJP (2024)
K.C. O’Donnell et al.Misinterpretations and omissions: a critical response to Goodwin and colleagues’ commentary on psilocybin-assisted therapy AJP (2024)
M.D. Alpert et al. Psychotherapy in psychedelic treatment: safe, evidence-based, and necessary AJP (2024)
G.M. Deckel et al. Psychedelic assisted therapy Must Not Be Retired AJP (2024)
E.E. Schenberg et al.I s poorly assisted psilocybin treatment an increasing risk? AJP (2024)
T. Leary et al. Reactions to psilocybin administered in a supportive environmentJ Nerv Ment Dis (1963)
R. Metzner et al. On programming psychedelic experiences Psychedelic Review (1967)
W.N. Pahnke et al. LSD-assisted psychotherapy with terminal cancer patients Curr Psychiatr Ther (1969)
I. Hartogsohn Constructing drug effects: a history of set and setting Drug Sci Policy Law (2017)
M.W. Johnson et al. Human hallucinogen research: guidelines for safety J Psychopharmacol (2008)
T.L. Golden et al. Effects of setting on psychedelic experiences, therapies, and outcomes: a rapid scoping review of the literature Curr Top Behav Neurosci (2022)
N. Schuitmaker Psilocybin-assisted therapy: a scoping review of participants’ and facilitators’ experiences in qualitative studies Res Soc Develop (2023)
S.L. Russ et al. States and traits related to the quality and consequences of psychedelic experiences Psychol Conscious Theory Res Pract (2019)
E.C.H.M. Haijen et al. Predicting responses to psychedelics: a prospective study Front Pharmacol (2018)
Carbonaro TM, Johnson MW, Hurwitz E, Griffiths RR. Double-blind comparison of the two hallucinogens psilocybin and…
T. Cowley-Court et al. Life after Ayahuasca: a qualitative analysis of the psychedelic integration experiences of 1630 Ayahuasca drinkers from a global survey Psychoactives (2023)
T. Noorani et al. Psychedelic therapy for smoking cessation: qualitative analysis of participant accounts J Psychopharmacol (2018)
M. Agrawal et al. Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder Cancer (2023)
M. Agrawal et al. Assessment of psilocybin therapy for patients with cancer and major depression disorder JAMA Oncol (2023)
There are more references available in the full text version of this article.