This Phase I/II study (n=52) tested a group retreat model of psilocybin therapy for people with metastatic cancer and anxiety or depression, using 25 mg psilocybin in a 3-day retreat format. No unattended distress episodes occurred, and anxiety and depression scores fell over 28 days.
Background:
Psilocybin is a promising therapy for cancer-related distress, but existing individual treatment models are resource intensive. In this study, we designed and tested a group model of psilocybin therapy for people with metastatic cancer and cancer-related anxiety and depression.
Method:
Eligibility criteria included metastatic cancer, moderate-to-severe symptoms of anxiety or depression without a pre-cancer mental health diagnosis, performance status adequate to attend a 3-day retreat that required self-care, and tapering of antidepressants. Exclusion criteria included enrollment in hospice. The design of the intervention included: two virtual preparatory sessions; a 3-day in-person retreat in a rustic setting that included the third prep session, the psilocybin session, and the first integration session; and two additional virtual integration sessions. Psilocybin was administered in oral capsules at 25 mg. A retreat team of four core facilitators and two backup facilitators conducted a series of eight retreats. The first retreat had five participants. For subsequent retreats, we used the primary safety outcome from each cohort, other safety outcomes, and qualitative feedback to make decisions to increase, decrease, or hold steady the participant number. The primary safety outcome was “unattended episodes of participant distress” during the psilocybin session requiring a backup facilitator. The primary exploratory efficacy outcome was reduction in anxiety and depression symptoms measured using the Hospital Anxiety and Depression Scale (HADS).
Results:
We enrolled 55 participants, of whom 3 withdrew prior to the retreat, leaving a total of 52. Their mean age was 53, and mean duration of living with cancer was 36 months, mean (range 5, 176); anticancer therapy was ongoing for 46 (88%); antidepressants were tapered for 18 (35%). The first retreat cohort had five participants, and the final retreat cohort had eight. For the primary safety outcome, there was not a single episode of unattended participant distress requiring a backup facilitator. The mean baseline at Day −14 (D −14) HADS total score was 17.5 (range 6–28); at D +28, the mean HADS total score was 10.2 (1–30), so the mean decrease in HADS from D −14 to D +28 was 7.3. (p < 0.0001).
Conclusion:
The Group Retreat Psilocybin Therapy was safe and well tolerated, and exploratory measures show efficacy that is promising. A group configuration of eight participants with four core facilitators can be safe for future studies with participants with serious medical illness.
Psilocybin has been investigated as a treatment for cancer-related anxiety, depression, and existential distress, and prior randomised studies of individual psilocybin therapy have shown benefit. However, the individual model is labour-intensive, typically requiring substantial therapist time per patient, which limits scalability. The authors note that group-based approaches might reduce resource demands while also adding potential therapeutic elements such as peer support, shared identity, group cohesion, trust, and a ceremonial sense of community. They also point out that very little prior cancer-specific research had tested psilocybin in a true group session format, particularly with all participants taking psilocybin together in the same room. L. and colleagues therefore designed Group Retreat Psilocybin Therapy to test whether a group retreat model could be delivered safely to people with metastatic cancer who had clinically significant anxiety and/or depression. The study aimed primarily to assess safety, especially the facilitator-to-participant ratio needed to support the session, and secondarily to collect exploratory efficacy outcomes on mood, distress, and aspects of the group experience. The paper presents this as a Phase 1/2 feasibility and safety study intended to inform future work. The authors also frame the intervention as a deliberate blend of retreat setting, ritual, and group process, developed to suit medically complex participants who were largely psychedelic-naïve and to see whether a group format could still support a meaningful psilocybin experience.
This was a single arm, open-label trial of Group Retreat Psilocybin Therapy in which a fixed number of facilitators worked with a varying number of participants in each cohort. For all the cohorts, two facilitators conducted the virtual preparation and integration sessions, and four facilitators plus two backup facilitators conducted the 3-day retreat. The prespecified primary safety outcome was "unattended episodes of participant distress" during the psilocybin session that required involvement of a backup facilitator. Over a series of eight cohorts, we used the primary safety outcome from each cohort, other secondary safety outcomes, and qualitative reports from participants to make decisions about whether to increase, decrease, or hold steady the number of participants enrolled in the next cohort. A trial guidance committee, including experts other than the investigators, provided guidance. Exploratory efficacy outcomes were also collected at baseline (D -14) and following the psilocybin session (D 0) at D +7, D +28, D +56, D +84, and D +180.
The eligibility criteria included: a diagnosis of a metastatic solid tumor for which evidence-based curative therapy was not available, or incurable hematological malignancy; age 18-85; Eastern Cooperative Oncology Group (ECOG) performance status 0-2; acceptable organ and bone marrow function with creatinine £ 1.5x normal; liver function tests £ 1.5• normal, hematocrit ‡ 20, platelet count ‡ 20 K; >4 weeks after surgery or radiation; interest in participating in a group study; and screening Hospital Anxiety and Depression Scale (HADS) total score of > 11 (indicating clinically significant symptoms of anxiety and/or depression). No prior high-dose psychedelic session in the past year was allowed; microdosing was allowed but would need to be stopped 2 weeks prior to starting the study intervention. Participants were required to taper off antidepressants prior to starting the study preparation sessions (to make this study comparable with other published studies with cancer patients), and to taper off scheduled benzodiazepines and cannabis products prior to the retreat (which may confound the effect of psilocybin on outcomes). Participants could continue intravenous (IV) anticancer regimens but had to be off for at least 7 days prior to the first day of the retreat or enough time so that their oncologist did not expect them to be neutropenic (absolute neutrophil count < 1000 cells/microliter); oral anticancer regimens were handled individually, with most being held on the day of the psilocybin session. Opioid pain medications, including scheduled and breakthrough doses, were allowed on the psilocybin day. The exclusion criteria included: enrollment in hospice, mental health diagnoses prior to the diagnosis of cancer requiring medication or clinical care (e.g., psychosis), family history of schizophrenia, and inability to self-care for the 3-day retreat. Recruitment was done using a study website, clinicaltrials.gov, and social media.
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Papers cited by this study that are also in Blossom
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Anderson, B. T., Danforth, A. L., Daroff, R. et al. · EClinicalMedicine (2020)
Kettner, H., Rosas, F. E., Timmermann, C. et al. · Frontiers in Pharmacology (2021)
Agrawal, M., Richards, B. D., Richards, W. A. et al. · Cancer (2023)
Lewis, B. R., Garland, E. L., Byrne, K. et al. · Journal of Pain and Symptom Management (2023)
Shnayder, S., Ameli, R., Sinaii, N. et al. · Journal of Affective Disorders (2023)
Trope, A., Anderson, B. T., Hooker, A. R. et al. · Journal of Psychoactive Drugs (2019)
Belser, A. B., Agin-Liebes, G. I., Swift, T. C. et al. · Journal of Humanistic Psychology (2017)
Back, A., Myers, S., Guy, J. et al. · Psychedelic Medicine (2024)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)
Roseman, L., Haijen, E. C. H. M., Idialu-Ikato, K. et al. · Journal of Psychopharmacology (2019)
Papers in Blossom that reference this study
Back, A. L., McGregor, B. A., Thorn, L. L. et al. · 2026
This was a single-arm, open-label Phase 1/2 study of Group Retreat Psilocybin Therapy. The intervention used a fixed facilitator team with a varying number of participants across eight cohorts, allowing the researchers to adjust group size over time based on safety findings and participant feedback. A trial guidance committee, including external experts, advised on these decisions. Eligibility criteria included metastatic solid tumours without curative treatment options, or incurable haematological malignancy; age 18-85; ECOG performance status 0-2; adequate organ and bone marrow function; at least 4 weeks since surgery or radiotherapy; willingness to take part in a group study; and a screening HADS total score above 11, indicating clinically significant anxiety and/or depression. Exclusions included hospice enrolment, certain pre-existing mental health conditions requiring care or medication, family history of schizophrenia, and inability to self-care during the 3-day retreat. Participants were also required to taper antidepressants before the preparatory sessions and to taper scheduled benzodiazepines and cannabis before the retreat. Recruitment used a study website, ClinicalTrials.gov, and social media. The intervention consisted of two virtual preparatory sessions, followed by a 3-day in-person retreat in a rustic natural setting, and then two virtual integration sessions. The retreat included a third preparation session, the psilocybin session, and the first integration session. Psilocybin was given as 25 mg oral capsules. The facilitation team comprised physicians, psychologists, psychotherapists, nurses, chaplains, and counsellors with relevant cancer-care, group-facilitation, contemplative, and altered-state experience. The researchers used Council-style group dialogue and a rites-of-passage framing with separation, liminal, and reincorporation phases, supported by ritual elements intended to promote psychological safety and engagement. The prespecified primary safety outcome was unattended episodes of participant distress during the psilocybin session, defined as a period when four participants needed 1:1 support at once and another participant was distressed without attention. Secondary safety questions assessed perceived adequacy of facilitator attention, response, and touch. Adverse events were recorded using standard oncology toxicity criteria and continuous facilitator observation. The primary exploratory efficacy outcome was change in HADS total score from baseline to Day +28, with additional measures including demoralisation (DS-II), death and dying distress (DADDS), psychosocial/spiritual well-being (NIH-HEALS), and quality of life (FACT-G). Psilocybin-experience measures included the MEQ30, CEQ, EBI, and Communitas scale. Analyses were mainly descriptive for safety; efficacy analyses used pre-post comparisons, including 1-sample t-tests for mean change scores. The study had ethical approval from the relevant regulatory and institutional bodies and was registered on ClinicalTrials.gov.
The researchers enrolled 55 participants, of whom 52 attended a retreat after three withdrawals before intervention. Participants had a mean age of 53 years, and the mean duration of living with cancer was 36 months. Most were receiving active anticancer therapy (46 participants, 88%), and 18 participants (35%) tapered antidepressants before the retreat. The cohort size increased over the study from 5 participants in the first retreat to 8 in the final retreats, reflecting the safety-guided adaptation process. On the primary safety outcome, there were no unattended episodes of participant distress requiring a backup facilitator during any psilocybin session. On the secondary safety questions, 100% of participants answered negatively to questions about not receiving enough attention, not getting an adequate response, or experiencing intrusive or unwanted talking or touching, and 100% said that other participants were supported adequately. There were no serious adverse events on the psilocybin day, including among the two participants with brain metastases. Reported events included transient malaise in two participants, nausea in two participants, and a migraine in one participant the day after dosing; later serious adverse events were judged unrelated to the intervention, including one hospitalisation for chemotherapy-related dehydration and two deaths from progressive cancer before final follow-up. There were no adverse events related to the preparation or integration sessions, and no instances of suicidality, depersonalisation, derealisation, or hallucinogen persisting perceptual disorder. For exploratory efficacy, mean HADS total score fell from 17.5 at Day -14 to 10.21 at Day +28, a mean decrease of 7.29 points (95% confidence interval -9.33 to -5.25; p<0.0001), indicating improved anxiety/depression symptoms. The DS-II also improved, with a mean decrease of 6.33 points at Day +28 and 5.47 points at Day +180, suggesting reduced demoralisation. FACT-G quality-of-life scores increased by 11.81 points at Day +28 and 9.85 points at Day +180. In the psilocybin-experience measures, participants reported high mystical-type experience scores on the MEQ30; 64.7% met the criterion for a complete mystical experience. Communitas scores suggested strong shared connection, while CEQ scores indicated moderate challenging experiences and EBI scores suggested substantial emotional breakthrough. The paper includes selective participant reflections illustrating death-related insight, vulnerability, group closeness, fear during difficult moments, emotional release, and appreciation of the ritual elements.
The authors interpret the findings as showing that Group Retreat Psilocybin Therapy can be delivered safely and feasibly in a retreat setting for people with metastatic cancer. They emphasise that no serious adverse events were attributed to the intervention and that no unattended distress occurred across eight retreats, which they present as the central result because it helps define a workable facilitator-to-participant ratio for future studies. They consider the exploratory efficacy findings encouraging, with reductions in HADS scores and improvements in demoralisation and quality of life. They suggest that the group format may have produced an experience of depth comparable to earlier individual psilocybin studies, although they note that direct comparisons are limited. They also point to the high MEQ30 and Communitas scores as consistent with strong mystical and communal aspects of the intervention. In their discussion of the retreat process, they argue that the combination of nature, ritual, ceremony, and group interaction may have supported safety and engagement. Relative to earlier research, the authors note that previous cancer psilocybin studies were individual rather than group-based, and that their sample differed in important ways because all participants had metastatic disease and most were receiving active anticancer therapy. They also compare their experience measures with earlier individual and naturalistic studies, while stating that such historical comparisons are not definitive. They conclude that the intervention may deserve further study and may expand access if future work can preserve safety with fewer resources than the individual model. The authors acknowledge several limitations. The sample was small, the study had no control group, it was single-site, and the facilitator team worked repeatedly together, which may limit generalisability and replication. They also note that the safety questions should ideally have been asked more than once after the retreat, and that participants might have been reluctant to report issues directly to facilitators. They state that the study procedures were manualised and refined to support future replication and scale-up, and that future retreats will use the safety questions electronically at additional timepoints.
The authors conclude that Group Retreat Psilocybin Therapy was safe and well tolerated, with promising exploratory efficacy findings. They state that a group configuration of eight participants with four core facilitators appears safe for future studies involving people with serious medical illness.
Facilitators were selected for: experience working with cancer patients in a clinical setting, group facilitation experience, a personal contemplative practice, and personal experience with non-ordinary states of consciousness. The multidisciplinary facilitators included physicians, clinical psychologists, masters trained psychotherapists, advanced registered nurse practitioners, chaplains, registered nurses, and licensed counselors (Master of Social Work, Licensed Clinical Social Worker, or Licensed Mental Health Counselor), all trained to the study protocol.
The intervention components included: (1) two virtual preparatory sessions; (2) a 3-day in-person retreat that included the third prep session, the psilocybin session, and the first-integration session; and (3) two additional virtual integration sessions. All sessions were manualized (manual available from the corresponding author). The physical setting was a rustic retreat center that has a 30-year history of doing cancer retreats, with individual rooms, shared bathrooms, a dining hall, a great hall for the group sessions, views of nature, short trails, and a labyrinth. Rescue medications were available (metoprolol, ondansetron, and lorazepam). At least one facilitator was Basic Life Support certified, and the retreat center had an automatic defibrillator adjacent to the room we used (which A.L.B. was trained to use). The retreat center was 20 min from the nearest Emergency Department. The facilitation model (described in Group Retreat Psilocybin Therapy for People with MetastaticCancer with Anxiety and Depression: A Rite of Passage Facilitation Model for a Phase1/2 Study) considered the entire intervention to be a rite of passage with three phases, as described by: (1) separation phase, (2) liminal phase, and (3) reincorporation phase. Our preparation sessions corresponded to "separation" (leaving one's normal routine); the psilocybin session corresponded to the "liminal" phase; the integration sessions corresponded to the "reintegration" phase. To enact the rites of passage facilitation model, the intervention included brief ritual elements that signaleded each phase, such as an opening circle poem to mark stepping away from one's usual routine; having participants bring symbolic objects to the psilocybin session that represented people or things that would remind them even while in a liminal space of why they choose to be in the study; and integration activities that reminded participants to bring their psilocybin session experiences and learnings back into their day-to-day life. Ritualized framing has been described in prior clinical trial contexts and therapeutic settings as a means of fostering psychological safety, promoting reflective states of mind, and enhancing engagement.The facilitation model and ritual elements were intended to invoke a contemplative, secular, person-oriented (rather than medically oriented) set and setting. The first preparation session began developing the mental "set" for the participants. The high-level objectives for preparation were to introduce group members to each other, articulate reasons for wanting to participate, discuss cancer-related experiences, and provide psychoeducation for the psilocybin experience. The group interaction for most sessions was based on Council practice, a structured form of group dialogue,and prior clinical trials of cancer support groups.In the version of Council used in this study, participants and providers convened on zoom or sat in a circle, used a talking piece (a physical object passed around a group to regulate the pace of conversation in a circle that encourages speakers and listeners to be more mindful, more reflective, and more self-aware), and responded to prompts given by facilitators (which are available in the Supplementary Data). Council differs from group psychotherapy in several important respects: as a modality is not designed to provide diagnosis, interpretation, or treatment of psychological disorders. Instead, it emphasizes equal participation, reflective listening, and speaking from personal experience in a non-hierarchical circle. Facilitators serve as guides for the process rather than as therapists analyzing content. Thus, we describe this intervention as "Group Retreat Psilocybin Therapy" rather than "group psychotherapy" or "assisted psychotherapy." The preparation also included practical and individual elements. Participants arrived at Day 1 of the 3-day retreat, for lunch, had group sessions that included psychoeducation about "what to expect," and a 30-min individual session to discuss anything they did not wish to bring up in the group, describe touch preferences, and have a suicidality assessment; this was followed by a group dinner and an evening session to get accustomed to their mattress, eye shade, and music, and to practice raising a hand for assistance. The psilocybin session, on Day 2, was designed to support participants for an experience of liminality which included uncertainty, emotional moments, and unexpected experiences. In the morning, there was a guided labyrinth walk, and then when they arrived at the hall, vital signs were taken, and psilocybin 25 mg oral capsules (Filament Health, Vancouver, BC) were administered in a brief ritual where participants spoke their intentions aloud. Blood pressure was measured pre-psilocybin and 1 h later, and followed if elevated. A playlist curated for this study (Wavepaths) was played over speakers. The facilitators moved around the room during the 7-h session to support all participants during the course of the day and provided support in response to explicit requests. (Participants were trained to raise their hand to request support and practiced this on Day 1.) Touch was offered according to the participant's preferences using previously published study guidelines.A study assistant tracked all interactions between facilitators and patients on a structured form. The psilocybin sessions were videorecorded for potential review if any incidents of compromised safety occurred. At the end of the session, snacks were offered followed by a brief closing circle. Participants were assessed before or after dinner to ascertain if extra attention was needed and had the phone number of a facilitator who was staying in the building on-call through the night. The integration sessions began formally on Day 3 of the retreat, when participants had a private session with a facilitator to tell the story of their psilocybin session, a group circle to share whatever part of their psilocybin experience they felt ready to talk about, a psychoeducation session about returning home, a session about how to continue integration at home, and a second brief private session for a safety check prior to leaving the retreat center. Following the retreat, there were two virtual integration sessions, designed to fulfill the "reincorporation" phase of a rite of passage, to enable participants to bring their insights into their everyday lives.
The primary safety outcome was "unattended episodes of participant distress," defined as a time period of any length during the group psilocybin session when four participants required 1:1 support simultaneously while another participant was experiencing distress that was unattended. The study assistant, who was trained to track interactions and record them on a structured form, watched for instances when a participant in a psilocybin session appeared to need 1:1 assistance, was not receiving it, and was becoming more distressed. All psilocybin sessions were videotaped so that these instances could be reviewed (this was not necessary). This outcome was measured with a study staff who logged all facilitator interactions with participants in real time. These timemotion logs were converted to visual diagrams showing interaction in 15-min blocks during the 7-h psilocybin session. The secondary safety outcomes were five questions that we developed after the first retreat and began using starting with the second retreat. The questions were: (1) Were there ever times when you felt you did not get the attention from the facilitators you needed to be safe?; (2) Were there ever times when you were having difficulty and the facilitators did not respond adequately?; (3) Were there ever times when a facilitator talked to you in a way that you found intrusive or unwanted?; (4) Were there ever times when a facilitator touched you in a way that you found confusing or unwanted?; and (5) As you look back now, do you feel that other participants were supported adequately by the facilitators? These questions were administered in person by a facilitator during a private meeting with the participant on the morning after the psilocybin session so that if a participant answered "yes" to any question, we could ascertain details of the event. Adverse events were collected using the National Cancer Institute Common Terminology Criteria for Adverse Events at the retreat, and facilitators continuously observed participants for adverse events, reporting them at twice-daily facilitator meetings. After the retreat, participant adverse events were collected after virtual integration sessions and as reported during interactions for measurement collection. The primary efficacy outcome was symptoms of depression and anxiety measured by the HADS.The HADS is a 14-item measure chosen because it was used in prior studies of psilocybin therapy for cancer, has been extensively validated in patients with cancer, and avoids somatic symptoms that could overlap with cancer-related fatigue. A decrease in HADS scores indicates improvement. The Demoralization Scale II (DS-II) is a 16-item self-report instrument designed to assess demoralization; each item is rated on a 3-point Likert scale, with total scores ranging from 0 to 32, where higher scores indicate greater demoralization. The Death and Dying Distress Scale (DADDS) is a 15-item measure used to assess distress related to thoughts of death and dying; each item is rated on a 6-point Likert scale, ranging from 0 ("no distress") to 5 ("extreme distress"), with total scores ranging from 0 to 75, where higher scores indicate greater distress. The National Institutes of Health Healing Experience of All Life Stressors (NIH-HEALS) was used to assess psychosocial and spiritual healing; each item is rated on a 5-point Likert scale, with higher scores indicating greater well-being. The Functional Assessment of Cancer Therapy-General (FACT-G) is a 27-item measure used to assess quality of 4 BACK ET AL. life that has been widely used in cancer studies.These measures were collected on a secure mobile app (Quantified Citizen) from baseline D -14 to 6 months D +180. Additional exploratory measures of the psilocybin experience were administered on paper on the morning of Day 3: Mystical Experience Questionnaire 30 (MEQ30), a 30-item self-report measure with scores from 0 to 150, with higher scores indicating greater mystical experience intensity; the Challenging Experience Questionnaire, a 26item self-report measure with scores from 0 to 130 with higher scores indicating more challenging experiencesthe Emotional Breakthrough Inventory (EBI), a 6-item measure with scores from 0 to 600, with higher scores indicating more profound emotional breakthroughs; and the Communitas scale, a 10-item measure with scores of 10-70 with higher scores indicating stronger group bonding.In addition to standardized quantitative outcomes, participants were invited to provide brief written reflections about their experience, and their Day 3 individual sessions were audio-recorded. A selection of quotes is presented alongside the retreat process quantitative results to provide an illustration of how these numerical results were experienced by participants, even though these do not represent a formal qualitative analysis.
Safety outcomes. Descriptive statistics were used to describe all safety outcomes, including "unattended psilocybin-related distress"; these outcomes were tabulated from the interaction worksheet immediately after each group intervention. Facilitator interactions. Descriptive statistics were used for facilitator interactions, which were coded during analysis as "simple" or "complex" using a definition developed during the course of the study. The data were visualized using Tableau software. Efficacy outcomes. For the primary exploratory efficacy measure of HADS total score, a pre-post strategy was used to compare the mean change from D -14 to D +28 using a 1-sample t-test. Mean changes (and standard deviation of the mean change) in HADS total score from D -14 to D +7, D +28, D +56, D +84, and D +180 after the psilocybin session (D 0) were also summarized. Mean changes from D -14 to D +28 for other measures were also summarized and assessed with 1-sample t test, and mean changes (with standard deviation of the mean change) from D -14 to other timepoints are presented descriptively.
This study was reviewed and approved by the Federal Drug Administration, the Fred Hutch Cancer Center Scientific Review Committee, and the Fred Hutch Internal Review Board. No information about study participation was entered into the University of Washington electronic medical record, and a Certificate of Confidentiality was obtained. This trial was registered at clinicaltrials.gov (NCT05847686).
Demographics. We enrolled 55 participants who committed to start the intervention and attend a retreat. Of those, 52 (90%) attended the retreat to which they were assigned (Fig.). Of the treated participants, 32 (61%) were female, 6 (12%) self-reported race or ethnicity other than White, and mean age was 53 years (range 26-81). Mean duration of living with cancer at study entry was 36 months (range 5, 176). Additional details are in Table. Anticancer therapy was ongoing for 46 (88%) participants, and included oral targeted therapy (23), IV targeted therapy (5), oral chemotherapy (3), IV chemotherapy (9), immunotherapy (7), and oral anti-hormonal therapy (10). Two patients had previously treated brain metastases (one with gamma knife and one with whole brain radiotherapy). Psychological or spiritual care had been provided by a palliative care clinician or counselor for 45 participants (74%). None were enrolled in hospice at study entry. Participant performance status was ECOG 0 for 5 (10%) participants, ECOG 1 for 43 (83%) participants, and ECOG 2 for 4 (8%) participants. Medications requiring taper. Eighteen (35%) participants were taking antidepressants for cancer-related depressive symptoms and tapered prior to the retreat. Three patients were taking medications for Attention Deficit / Hyperactivity Disorder (ADHD), which they stopped 1 day prior to the retreat. Seven (13%) participants reported some use of cannabis products and were advised to discontinue them. Among cannabis users, all five reported using it for sleep. One participant began using high-dose cannabis in the month prior to the retreat because of worsening anxiety after tapering their sertraline, without informing the investigators. Medications allowed for symptoms. Participants' ongoing treatments for pain included: opioid-responsive pain, for which scheduled and breakthrough opioids were used by 9 (17%), allowed during the psilocybin session and not tapered; neuropathic pain for which a gabapentoid was used and tapered, 5 (10%); 2 had been treated with lutetium radioligand therapy more than 4 weeks prior to study entry. Past experience with psilocybin included 21 (40%), who reported using "magic mushrooms" as young adults in high school or college. No participant reported a psilocybin experience within the past 15 years, including microdosing, or since their cancer was diagnosed (Fig.).
The trial design prespecified that all retreats would have four core facilitators and two backup facilitators, with the number of participants per cohort varying according to safety outcomes. Over the eight cohorts, the number of participants increased from five to eight (Table). The number of participants per cohort who actually attended a retreat was as follows: Cohort 1 (C1) = 5 participants; C2 = 6; C3 = 6; C4 = 6; C5 = 7; C6 = 6 (there was a last-minute dropout); C7 = 8; C8 = 8. Note that 55 participants enrolled, of whom 1 withdrew before the intervention started, 1 withdrew just before the Cohort 1 retreat, and 1 withdrew just before the Cohort 6 retreat, leaving 52 participants who completed the intervention.
Primary safety outcome. For the primary outcome of "unattended episodes of participant distress" during the psilocybin session, when more than four participants required core facilitator intervention, not a single instance was recorded. Other safety outcomes. The questions regarding participants' perceptions of facilitator availability and safety during the psilocybin session specifically were as follows: (1) Were there ever times when you felt you did not get the attention from the facilitators you needed to be safe? (No, 100%); (2) Were there ever times when you were having difficulty and the facilitators did not respond adequately? (No, 100%); (3) Were there ever times when a facilitator talked to you in a way that you found intrusive or unwanted? (No, 100%); (4) Were there ever times when a facilitator touched you in a way that you found confusing or unwanted? (No, 100%); 5) As you look back now, do you
feel that other participants were supported adequately by the facilitators? (Yes, 100%). Adverse events. There were no serious adverse events on the psilocybin day (Table), including for the two participants with brain metastases. Use of scheduled opioids did not result in adverse events. Of the two patients who experienced malaise as the psilocybin session ended, one was later found to be using high-dose cannabis until the day before, unreported to study staff, and one tested positive for Coronavirus (COVID) infection the following day (no other participants or study personnel acquired infections; all had a negative COVID test on arrival at the retreat). Of the two patients experiencing nausea, one was treated with ondansetron (an anti-nausea medication) with no benefit. On the day after the psilocybin session, one patient (with a history of migraines) had a migraine and used their prescribed sumatriptan with relief. After the psilocybin session, there were three serious adverse events, none related to the Group Retreat Psilocybin Therapy: one patient was hospitalized for chemotherapyrelated dehydration 7 days after the retreat; two patients died of progressive cancer before the last followup at D+180. There were no adverse events related to preparation or integration sessions. There were no instances of suicidality. There were no participants who experienced depersonalization, derealization, or hallucinogen persisting perceptual disorder.
Primary exploratory efficacy outcome: change in the mean HADS score. The mean (standard deviation) HADS baseline D -14 total score among all treated participants was 17.5 (5.99); at D +28, the mean HADS total score was 10.21 (6.31) with a mean decrease from D -14 to -7.29 (95% confidence interval, -9.33, -5.25; SD - The DS-II mean D -14 score was 13.2 (range 2-32); at D +28, the mean DS-II was 6.8 with a mean decrease of -6.33, suggesting improvement in demoralization. The mean decrease from D -14 to D +180 in the DS-II score was -5.47. The FACT-G mean D -14 score was 62.3 (range 33-93); at D +28, the mean FACT-G was 74.1, with a mean increase of 11.81, suggesting improvement in quality of life. The mean increase from D -14 to D +180 in the FACT-G score was 9.85.
To describe facilitator interactions, we developed a distinction during the study between "simple" and "complex" interactions. In a simple interaction, the participant maintains adequate self-regulation through a strong emotion or difficult experience, and the facilitator provides non-directive presence or empathic support. In a complex interaction, the participant shows impaired selfregulation, and the facilitator initiates directive intervention to support emotional expression, reduce distress, or ensure safety. The average number of simple + complex facilitator interactions per participant for all cohorts was 8.1, and most of those interactions were coded as simple (average 5.9). While 22 (42%) participants had zero complex facilitator interactions, 20 (38%) had at least one complex facilitator interaction lasting £ 45 min, and 10 (19%) had a prolonged complex facilitator interaction lasting > 45 min (with facilitators rotating about every 30 min). Figureshows the average number of simple + complex facilitator interactions per cohort for all eight cohorts combined over each 15-min segment of their psilocybin session. Although the cohorts had different numbers of participants, the number of facilitators was fixed, so these numbers represent facilitator demand. The Fig.. Facilitator interactions over time for all cohorts. Facilitator interactions for each 15-min interval during the psilocybin session. All sessions had four core facilitators and two backup facilitators. Each bar shows the average number of facilitator interactions per cohort for each 15-min segment of a psilocybin session, where time = 0 is when psilocybin was administered, and time = 7 h is the end of the session. The required blood pressure measurements are not included in these data. The color scale of the bars reflects the average number of facilitator interactions, where the color white indicates the lowest value, and the dark red indicates the highest value. The black dots represent the maximum number of facilitator interactions observed in all eight psilocybin sessions. Both instances where five facilitator interactions were recorded within a 15-min period did "not" qualify for the primary safety outcome because in both cases at least two of the facilitator interactions did not require the entire 15-min period, so that no backup facilitators were called in.
Supplementary Data include a heatmap showing simple + complex interactions for each cohort. On the MEQ30, participants reported high levels of mystical-type psilocybin experiences. The mean (-SD) total MEQ30 score was 3.61 -0.97. Subscale means were: 3.55 -1.02 for Mystical, 3.57 -1.16 for Positive Mood, 3.81 -0.82 for Transcendence of Time and Space, and 3.63 -1.16 for Ineffability. Overall, 64.7% of participants met the criterion for a "complete mystical experience" as defined by Barrett.The MEQ30 mean, raw total score was 108 -29.1. Participant reflection: "I wrestled with the idea of death and it didn't seem possible to die. It felt like my body could die, but my feelings could never die and, I know this sounds silly but I realized that death is love." On the Communitas Scale, participants reported strong feelings of collective connection and shared experience. The mean (-SD) total Communitas score was 56.5 -10.0. (The instructions for the Communitas Score instructed participants to rate only the psilocybin session.) Participant reflection about the group: "There is a lot to be gained. . .just being willing to engage and be vulnerable-this is awesome." Another reflection: "I love the whole idea of the group and all that we went through and the intimacy that we had." On the Challenging Experiences Questionnaire (CEQ), participants reported moderate levels of difficult experiences. The mean (-SD) total CEQ score was 1.60 -0.93. Subscale means were 1.70 -0.99 for Fear, 1.38 -1.29 for Grief, 1.62 -0.84 for Physical Distress, 1.37 -1.21 for Insanity, 1.50 -1.24 for Isolation, and 2.61 -1.16 for Death. The mean, raw total score was 41.7 -24.1. Participant reflection: "I felt like I was twisting into the ground. . .I got scared, I was freaking out, I wasn't ready yet. . ." On the EBI, participants reported substantial emotional breakthrough, with a mean (-SD) score of 70.0 -23.0. Participant reflection: "I objectified my cancer and wanted to be angry at it and yell and scream and then started laughing at how absurd that was. So I gave it a hug and loved and forgave." While we did not have an instrument to measure the effect of ritual, many participants described the ritual elements as contributing to a sense of calm and shared purpose, which helped them feel prepared for their psilocybin experience and integration. Participant reflection: "I've always been, well, [the ritual elements] are a hokey kind of thing, right? But I really liked the exercise of putting what we wanted to leave behind in the rock."
We conducted this Phase 1/2 study of the Group Retreat Psilocybin Therapy to examine safety outcomes and exploratory efficacy outcomes using an intervention design that brings in elements of nature, ritual, and ceremony adapted for participants who are medically complex and largely psychedelic-naïve. In particular, we sought to identify a safe facilitator-to-participant ratio to be used in future studies that could potentially increase access, while taking safety, efficacy, and logistical considerations into account. The safety outcomes were the most important, especially given the setting outside a medical facility, and demonstrate that Group Retreat Psilocybin Therapy is safe and feasible. Over the course of eight retreats, we encountered no serious adverse events attributed to the intervention, and not a single instance of "unaddressed psilocybin-related distress" was observed during a psilocybin session. The adverse events we did encounter during the psilocybin sessions were managed mostly with facilitator interactions. We did encounter a learning curve for the facilitator team, which is reflected in Tableshowing how cohort numbers were increased. The efficacy outcomes for the Group Retreat Psilocybin Therapy, while exploratory, are promising, even though our participant sample differs from other published studies with cancer patients. For example, the randomized study of psilocybin for cancer patients with anxiety and depression by Ross et al.involved 29 patients, of whom 10 (34%) had stage IV cancer; in this study, 52 (100%) had metastatic cancer, with 2 dying of progressive cancer before the 6-month follow-up was complete. Ross et al. do not report how many participants had ongoing anticancer treatment; in this study, 88% were undergoing anticancer therapy that had to be paused or adapted so they could participate. Despite these differences, the efficacy of this study may be comparable. In Ross et al., the exact HADS total scores are not reported, but The strengths of this study are that the intervention was manualized, used facilitators with relevant experience, and followed a predefined scheme for increasing the number of participants per cohort. Another strength is the careful tracking and documentation of facilitator interactions. Finally, the exploratory efficacy outcomes used measures that are validated and being used in other studies, and the FACT-G provides a benchmark for comparisons to future studies. Overall, Group Retreat Psilocybin Therapy merits further study. Compared with an individual setting, the group format makes different demands of participants: They need to listen to other patient's stories about living with metastatic cancer and facing mortality that are somewhat different than their own; they need to interact with the other participants; and they also need to interact with all the facilitators. An earlier individual study of psilocybin for patients with cancer reported mean MEQ scores of 60-70 (Fig., exact scores not reported); in this study, mean MEQ score was 108. A study using the Communitas instrument in naturalistic settings with different populations reported a total score of 39.6; in this study, the Communitas score was 49.5. While these historical comparisons are not definitive, they suggest that this intervention offers an experience comparable in depth with individual psilocybin and a group experience comparable with what has been reported in naturalistic studies. However, there are likely patients for whom this group intervention or natural setting would not be suitable. This study also has limitations. The study involved a relatively small sample of patients with metastatic cancer, and there was no control group, so the generalizability of these findings is limited. Given the lack of safety data that exist for group psilocybin interventions, we felt it was important to establish safety as a first step. In addition, the study was conducted at a single site, with a cadre of facilitators who worked together repeatedly over a year. That may not be possible to replicate exactly, but we did manualize the study procedures and refine them continuously, so that materials have now been created to replicate and scale this intervention as well as train future facilitators. Finally, we acknowledge that the safety questions should be asked more than once after the retreat and that participants may have concerns about reporting safety issues to one of the facilitators. However, we now have data that the safety questions were clear and easily understood, and in future retreats, we will use them in an electronic format with additional timepoints.
Group Retreat Psilocybin Therapy was safe and welltolerated, and exploratory measures show efficacy that is promising and merits further study. A group configuration of eight participants with four core facilitators can be safe for use in future studies with participants with serious medical illness.