Set and setting in psilocybin-assisted therapy: A qualitative study of patients with cancer and depression

Interest in psychedelic-assisted therapy (PAT) has renewed attention to the non‑pharmacological elements that accompany drug administration, commonly framed as "set" (patients' mindset) and "setting" (the treatment environment). Earlier research and contemporary models suggest these contextual factors shape subjective experiences and hence therapeutic outcomes, but empirical, especially qualitative, investigations of how set and setting influence acceptability and patient experience in PAT are scarce. Debates persist about whether preparatory work, therapist presence, music, ritualised elements and integration practices are merely safety scaffolds or active contributors to efficacy. Beaussant and colleagues set out to explore how elements of therapeutic context shaped acceptability, perceived safety and therapeutic benefit among patients with cancer and major depressive disorder who participated in a Phase II open‑label psilocybin trial. Using semi‑structured exit interviews, the study examined participants' perspectives on preparation, dosing‑day environment, music, therapist support, and integration practices, aiming to generate empirical insights into the interplay between the psilocybin experience and its therapeutic container to inform optimisation of PAT delivery.

This study is a qualitative companion (the ACCEPT Study) to a single‑centre, Phase II open‑label parent trial of psilocybin‑assisted therapy in adults with cancer and major depressive disorder (NCT04593563). The parent trial protocol combined group‑based preparation, simultaneous administration of psilocybin 25 mg (participants dosed at the same time in adjacent rooms with dedicated therapists), and group plus individual integration sessions; the treatment spaces were intentionally non‑clinical, and a standardised music programme was used during sessions. All 30 individuals who completed the parent trial were invited to the ACCEPT Study; 28 consented and took part, providing a convenience sample. Semi‑structured interviews were conducted virtually via Zoom between January and November 2021, typically 2.9 months (range 2.1–5.1) after dosing. Interviews were audio‑recorded and professionally transcribed. The interview guide covered participants' experiences of the psilocybin effect and perspectives on therapeutic factors relevant to acceptability. Analyses used a combined inductive–deductive template analysis. An a priori coding template drew on a conceptual framework of acceptability and set/setting constructs; two coders independently coded the first eight transcripts to refine the template, then coded remaining transcripts with bi‑weekly team meetings to resolve discrepancies and refine the codebook. The team sought code‑level saturation and used peer debriefing and analytic memos to enhance trustworthiness. Dedoose software (v9.0.54) was used to manage and analyse qualitative data. The research received institutional review board approval and participants provided separate informed consent for the ACCEPT Study.

Twenty‑eight participants completed semi‑structured exit interviews; a table of participant characteristics is referenced but not fully reproduced in the extracted text. Analysis yielded three overarching interrelated themes: (1) acceptability of the psilocybin experience, framed by surrendering to its intensity within a safe supportive setting; (2) the importance of therapeutic structure — preparation, aspects of the dosing‑day setting, and integration — in fostering acceptability; and (3) the role of integrated medical and ceremonial components in acknowledging and deepening cancer‑related and existential dimensions of the experience. On the first theme, participants consistently described the psilocybin session as physically, emotionally and existentially intense and demanding; many nevertheless viewed this demandingness as integral to healing. Reported sensations ranged from profound grief and terror to bliss and clarity, alongside somatic effects such as nausea, cramps or tremors. Several participants used strong metaphors (for example, likening the intensity to being "run over by a steam roller" or to childbirth and death) to convey its force. A second subtheme captured a tension between resistance and surrender: some participants described a natural impulse to resist overwhelming effects, while preparatory work and a felt sense of safety enabled many to transform resistance into a deliberate act of surrender, which they retrospectively saw as therapeutic. The third subtheme highlighted altered vulnerability, dependence and suggestibility under psilocybin; participants emphasised that feelings of safety and trust in therapists and the environment were crucial to allow them to be witnessed and dependent without harm. Although one participant reflected on the theoretical risk of exploitation in such vulnerable states, none reported experiencing abuse. The second major theme focused on therapeutic structure. Preparation sessions were widely valued for meeting informational and emotional needs and for building trust with therapists, though some participants wished for more or differently tailored preparation, especially regarding somatic or non‑visionary experiences. Dosing‑day elements (room design, therapist presence, music and the simultaneous administration format) were reported as both enhancing and, in some cases, hindering experience; participants noted cultural and religious background shaped how music and other sensory features were experienced. Integration — delivered via two post‑dosing visits comprising group and individual sessions, plus encouragement of personal practices (journalling, reading, nature, listening to the session soundtrack) — was described as critical for consolidating meaning and translating insights into daily life. The third theme addressed the interplay between clinical and ceremonial elements. Participants valued symbolic features (for example a chalice, rose and ritualised moments at administration) that imparted reverence and differentiated the experience from routine medical care, while also finding comfort in the controlled, professional medical setting. Views varied: some participants wanted a more nature‑based or ritual‑heavy approach, whereas others preferred the medical balance. Music emerged as a powerful but variable influence; for some it guided emotional processing, for others it felt culturally incongruent or overly directive. Overall, participants reported that the combination of structure, skilled therapist presence and symbolic elements supported acceptability and meaning‑making.

Beaussant and colleagues interpret their findings as supporting a conceptual model in which psilocybin's intense effects become therapeutically acceptable through the intertwined processes of surrender, structured support, and meaning‑making. They argue that participants often experienced the intensity of psilocybin — physically and existentially demanding — as central rather than merely adverse, with emotionally difficult moments facilitating breakthroughs consistent with prior reports of cathartic therapeutic processes. The researchers emphasise that surrender functioned as a cultivated capacity, enabled by preparatory work, therapist presence and environmental safety; trust in the therapeutic alliance was presented as a necessary condition for letting go. This leads them to caution against scaling approaches that minimise therapist involvement, since participants identified therapist integrity and presence as foundational to both safety and efficacy. The discussion also foregrounds ethical concerns: heightened vulnerability and suggestibility during altered states create power differentials and potential for boundary violations, so the authors call for heightened ethical vigilance, reinforced boundaries and careful handling of supportive touch and interpersonal pacing. Further, the authors highlight pragmatic matters for therapeutic design. Preparation and integration were portrayed as essential but variably sufficient, suggesting need for more flexible and individualised approaches that acknowledge experiences that may defy prior explanation or facile integration. Music, while often described as emotionally guiding, was shown to be culturally and personally variable in effect, prompting a recommendation for nuanced musical literacy and adaptive programming. The balance between ceremonial and medical elements was framed as both beneficial and challenging: symbolic, ritualised features imparted reverence and aided meaning‑making for many, yet some participants desired more naturalistic or spiritual framing. Beaussant and colleagues suggest interdisciplinary collaboration (for example with chaplains, Indigenous practitioners and ethicists) to refine spiritual components while respecting diverse cultural lineages. In positioning these findings within broader debates, the authors contend that psilocybin acts as a catalyst whose therapeutic potential is shaped and potentiated by relational, environmental and meaning‑based factors, not solely by neuropharmacology. They acknowledge limitations in generalisability given the study's secondary‑analysis design, self‑selection, and its focus on people with both cancer and MDD, and they note the interpretive nature of qualitative research while recommending mixed‑methods and longitudinal work to further clarify how structure, culture and individual differences shape outcomes.

The authors conclude that acceptability and therapeutic impact of psilocybin‑assisted therapy depend on a carefully designed therapeutic container that enables trust, surrender and meaning‑making. When intense, often existentially challenging experiences were embedded within relational safety, skilled preparation and thoughtful integration, participants found them acceptable and potentially transformative. Beaussant and colleagues call for ethical, flexible and patient‑centred models of care that integrate psychological, medical and spiritual dimensions to preserve healing potential while protecting participant well‑being as PAT moves toward broader clinical implementation.