Second group psilocybin retreat for people with partial response after the first experience: a phase 1 study

We sought input from participants in our first group retreat psilocybin study as consultants in planning the feasibility and conduct of this study by soliciting brief (approximately 30 min) qualitative interviews specifically on this topic prior to recruitment from 5 participants of BACK002. Participant input was crucial in three design decisions: assessing interest in having a second experience, removing the requirement to taper antidepressants, and extending the integration period from three to four group sessions over a longer time frame.

This was a single-arm Phase 1 study designed to assess the safety of a second psilocybin group retreat experience for patients with metastatic cancer who had participated in and had a partial response to our prior study (BACK002). The study was conducted under FDA Investigational New Drug authorization (IND 165562) and was approved by the Fred Hutchinson Cancer Center Institutional Review Board. The trial was registered at ClinicalTrials.gov↗ (NCT06644170↗). All participants provided written informed consent.

One change was made to the eligibility criteria after initial IRB approval and before recruitment began, based on patient consultant input: we added a fourth criterion allowing participants who had experienced recurrence of anxiety or depression symptoms after completing the six-month follow-up of the first study. No other protocol changes were made during the conduct of the trial.

Participants were eligible if they had participated in our prior group retreat psilocybin study (BACK002) and met at least one of four partial response criteria: (1) MEQ score below the threshold for a “complete” mystical experience (less than 60% of maximum score); (2) HADS Total change from Day −14 to Day +28 in the first study showing worsening symptoms (defined as increase HADS Total score >2 points) or minimal response (improvement of 5 points or less); (3) HADS Total score at Day +28 in the first study of 11 or greater, indicating persistent moderate-to-severe symptoms; or (4) recurrence of symptoms of anxiety or depression (HADS total score > 11) after completing the six-month follow-up of the first study.

Key inclusion criteria included: diagnosis of metastatic solid tumor or incurable hematologic malignancy; age 18–85 years; ECOG performance status 0–2; HADS Total score of 11 or greater at screening; and ability to participate effectively in a group setting. Key exclusion criteria included: untreated brain metastases; personal or immediate family history of schizophrenia, bipolar disorder, or other primary psychotic disorders; suicidal ideation with Columbia Suicide Severity Rating Scale (C-SSRS) score of 3 or greater; current substance use disorder; QTc interval greater than 450 ms (a risk factor for cardiac arrhythmias); and concurrent use of monoamine oxidase inhibitors or medications that prolong the QTc interval.

Notably, unlike our prior group study, participants were ^*not^* required to taper antidepressant medications and were allowed to continue these medications throughout the study.

The study was conducted at a rustic retreat center located approximately 2 h from Seattle, Washington (The Whidbey Institute). This non-clinical setting was selected to provide a comfortable, nature-based environment conducive to the therapeutic process while maintaining all necessary safety provisions, including access to emergency medical services and 24-h on-call cardiology consultation.

The intervention consisted of group retreat psilocybin therapy delivered over a three-day retreat, embedded within a structured program of preparation and integration sessions (Figure 1). Detailed descriptions have been published elsewhere (10, 11). The Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) checklist for reporting set and setting is included in the Supplementary material (29).

Of the 52 participants who completed the prior study (BACK002), 19 met at least one partial response criterion and were potentially eligible. Of these, 19 expressed preliminary interest in participating, 19 were screened, and 15 were enrolled. The average time from their first psilocybin session in BACK002 to their second psilocybin session in BACK004 was 15.3 months (range 10–20 months). The CONSORT diagram is in Figure 2, Of the 15 enrolled participants, one participant developed acute COVID-19 infection prior to the retreat and was unable to attend, and one other participant experienced a rapidly declining functional status after enrollment and was unable to attend. Consequently, thirteen participants attended a three day retreat, completed the psilocybin session and entered the integration phase. Twelve of 13 treated participants completed all study assessments through the 24-week follow-up (Figure 2), except for 1 participant who had medical complications precluding her Month 2 questionnaires, and died of progressive cancer prior to the Month 6 questionnaires.

Recruitment occurred from October 2024 through March 2025. The retreats were conducted in February and March 2025. Follow-up questionnaires were completed in October 2025.

Table 1 presents baseline demographic and clinical characteristics of the participants who attended a retreat. These 13 participants met the partial response criteria as follows: 9 participants met Criterion 1 (MEQ below complete threshold); 0 met Criterion 2 (minimal or negative HADS change); 1 met Criterion 3 (HADS > 11 at Day +28); and 3 met Criterion 4 (symptom recurrence after 6-month follow-up).

Their mean age was 56 years (range 33–66); 9 (70%) were female. All participants identified as White, with 1 (8%) identifying as Hispanic. Cancer types included gastrointestinal (31%), breast (23%), gynecological (23%), and other (sarcoma, thyroid, myeloma; 23%). Mean duration living with cancer was 47 months (range 18–87). Eleven participants (85%) were receiving active anticancer therapy during the study period.

Five participants (38%) were taking antidepressant medications (bupropion, n = 4; duloxetine, n = 1) and continued these medications throughout the study without tapering. These five participants had all been taking the same antidepressant prior to BACK002 (the prior study), had tapered for that first psilocybin session, and resumed taking them during the integration period.

All 13 participants completed the three preparation sessions and received the 35 mg psilocybin dose. Seven participants (54%) received the 10 mg booster dose after meeting safety criteria and reporting low subjective drug effect at 60–90 min. Of these seven, 3 were taking concurrent antidepressants. All participants completed the four group integration sessions.

No serious adverse events occurred. No moderate or severe adverse events attributable to psilocybin were observed. There were no instances of suicidal ideation, psychotic symptoms, or prolonged psychological distress requiring pharmacological intervention.

Mild adverse events for participants who attended the retreat are summarized in Table 2. Four participants experienced transient asymptomatic hypertension (blood pressure elevated above baseline but below 150/90 mm Hg). Three participants experienced nausea (mild in two, moderate in one; the participant with moderate nausea received ondansetron). One participant experienced self-limited somatic shaking during the session. One participant with a history of migraines experienced a mild headache at the end of the dosing session and self-administered their own rizatriptan. One participant, who had attended a family funeral the day before the retreat, experienced a prolonged but uncomplicated drug effect; they remained recumbent at the end of the dosing session but were responsive and oriented, participated in dinner, retired normally, and reported feeling well the following morning.

All seven participants who received the booster dose tolerated it without serious or moderate adverse events. Among these seven participants, one experienced asymptomatic hypertension post-booster, one experienced moderate nausea, one experienced a mild headache, and one experienced prolonged drug effect (all described above). Table 3 presents QTc interval changes from screening to post-initial-dose assessment (just prior to booster administration). Mean QTc change was +1 ms (range −29 to +26 ms). After their initial psilocybin dose, no participant who wanted to be assessed for a booster had QTc prolongation above 450 ms that would have precluded booster administration. Two of the participants who received a booster were taking bupropion; one participant who received a booster was taking duloxetine.

The safety profile observed in this study was reassuring and consistent with our prior study and the broader psilocybin literature. No participants experienced serious adverse events, psychotic symptoms, suicidal ideation, or psychological distress requiring pharmacological intervention. The adverse events that did occur—transient hypertension, nausea, headache, and one prolonged but uncomplicated drug effect—were mild and self-limited, consistent with the known acute effects of psilocybin (15, 16).

The higher starting dose of 35 mg and the availability of a 10 mg booster dose did not introduce new safety concerns. Seven participants (54%) received the booster dose, and all tolerated it well. The safety screening protocol—requiring ambulation, acceptable vital signs, absence of serotonin syndrome signs, and QTc less than 450 ms—proved practical to implement in the group retreat setting. Mean QTc change at the time of booster assessment was not clinically significant at only +1 ms, and no participant was excluded from receiving the booster due to QTc prolongation. These findings support the feasibility of individualized booster dosing within a group treatment model, and suggest that a QTc measurement at the time of booster administration is unnecessary.

A notable feature of this study was that participants were not required to taper antidepressant medications—a departure from most psilocybin clinical trials. Five participants (38%) continued their antidepressants throughout the study, and there were no safety concerns in this subgroup. This finding is clinically important because in our prior study, antidepressant tapering resulted in increased symptom burden prior to the psilocybin session for at least 3 participants. In addition, participants who had tapered antidepressants had a non-significant trend toward reduced MEQ scores and poorer HADS outcomes. Thus for the present study, we hypothesized that the combination of a higher dose, an available booster, and no tapering requirement might yield better outcomes than tapering followed by a lower dose.

The most striking finding may be the substantial increase in mystical experience scores from the first to second psilocybin session. Mean MEQ scores increased from 77 to 107, and the proportion achieving a complete mystical experience (≥60% of maximum score) increased from 38% to 77%. This improvement occurred despite—or perhaps because of—the fact that these participants were specifically selected as partial responders to their first experience.

Notably, 9 of the 13 participants were eligible for this second experience study because of a low MEQ score at their first experience, but in their second experience, their MEQ scores increased from a mean of 76.0 in their first experience to mean 98.15 in their second experience. The proportion of participants whose MEQ scores qualified as a “complete” mystical experience doubled from 38% in their first experience to 77% in their second experience. These results suggest that for partial responders after a first experience, a second experience appears to allow them to have a more “mystical” experience, which has been associated with lasting benefit.

Several factors may have contributed to this enhancement. The higher starting dose (35 mg vs. 25 mg) and availability of a booster dose likely increased the pharmacological intensity of the experience for some participants. The absence of antidepressant tapering may have allowed participants to enter the experience with a more stable psychological baseline. Participants' prior experience with the group retreat format may have reduced anticipatory anxiety and allowed greater psychological surrender to the experience. Finally, the established relationships that participants had with the facilitation team may have created an especially supportive interpersonal context, even though they were in different cohorts for their first experience.

Importantly, the increase in mystical experience intensity was not accompanied by an increase in challenging experiences. Mean Challenging Experiences Questionnaire scores were nearly identical between the first and second experiences, suggesting that the enhanced mystical experience did not come at the cost of increased psychological difficulty.

The exploratory efficacy outcomes were encouraging. Although this Phase 1 study was not powered to detect efficacy, the observed improvements in symptoms of anxiety and depression are noteworthy. The HADS Total scores decreased by 7 points at Day +8, with this improvement maintained through the 24 week followup. Since the minimal clinically important difference in the HADS was 1.7 in a study of patients with serious illness (cardiovascular) (30), this improvement is clinically significant. In addition, the 7-point reduction in HADS Total scores is comparable in magnitude to effects observed for a first psilocybin therapy experience in randomized controlled trials of individual psilocybin therapy for cancer-related distress (5–7). In this second experience study, 69% of participants achieved HADS Total scores below 11—the threshold for clinically significant symptoms—at Day +8.

The trajectory of HADS scores revealed some complexity. Two participants experienced increases in HADS scores between Day +8 and Day +36 that were attributable to external life stressors unrelated to their own cancer—one participant was dealing with grief from a close relative's death; another had been invited to become a peer counselor for other patients with little instruction and experienced distress that they attributed to the responsibility of this unfamiliar role. These cases illustrate that the stresses of living with advanced cancer do not occur in isolation, and that people living with cancer face a succession of challenges.

Measures of death anxiety (DADDS), demoralization (DSII), quality of life (FACT), and adjustment disorder (ADNM20) changed, on average, in the direction of clinical improvement. We did not test these changes statistically because this was a small single-arm safety study. However, these scores may not tell the entire story; even when individual quantitative scores suggested no change or even negative, every participant felt that their second experience was a valuable continuation of their first experience in their ongoing psychospiritual adjustment to living with cancer.

Measures of social processes in this study also provide preliminary evidence that some benefits of the group retreat model are the result of enhanced social connection and group cohesion. Social support scores increased progressively from baseline through Day +8 and were maintained at 24 weeks. Social identification—the sense of belonging to and identifying with the group—showed a similar pattern. Group cohesion scores, not measured at the pre-Prep 1 baseline, were measured from Day −1 onward, were high throughout, increasing slightly after the psilocybin session.

These social process measures were not collected in the first experience study, so direct comparison is not possible. However, the Communitas Scale—which assesses the sense of an experience of community during the psilocybin session—showed substantially higher scores in the second experience compared to the first (mean increase of 15 points, with 11 of 13 participants showing increases). Further research is needed to examine the how preparation and retreat design may enhance the power of social processes in group psilocybin therapy.

These findings have several implications for the developing field of psilocybin therapy. First, they suggest that partial response to a single psilocybin therapy session need not be considered a psilocybin therapy treatment failure. Psilocybin therapy may benefit from dose optimization and retreatment for some patients.

Second, the safety of higher doses and booster dosing in a group setting suggests that individualized dosing protocols may be feasible in future clinical implementations. The safety screening protocol used in this study—practical enough to implement during a group retreat—could serve as a model for clinical programs seeking to optimize dosing for individual patients.

Third, the feasibility of maintaining antidepressant medications has important implications for access. Many patients with cancer-related distress are already taking antidepressants, and requiring tapering creates a significant barrier—both logistically and because of the distress that tapering can cause. If future studies confirm that beneficial outcomes can be achieved with appropriate psilocybin dose adjustments rather than tapering of antidepressants, this may reduce a barrier to psilocybin therapy.

Fourth, the enhanced social outcomes observed in this study support continued investigation of group treatment models. If the group retreat format provides therapeutic benefits beyond those of individual treatment—through enhanced social connection, shared meaning-making, and mutual support—this could help justify the additional complexity of group logistics while substantially improving cost-effectiveness and access.

This study has several important limitations. The single-arm design without a control group precludes causal inference about efficacy. The small sample size limits statistical power and precision of effect estimates, and precludes meaningful subgroup analyses (e.g., comparing outcomes in those who did vs. did not receive the booster, or those on vs. off antidepressants).

The study population was highly selected: all participants had previously completed a psilocybin therapy study, were motivated to have a second experience, and had demonstrated ability to participate effectively in a group format. The lack of racial, and ethnic diversity (all participants identified as White) limits generalizability to broader populations and reflects ongoing challenges in ensuring equitable access to psychedelic research.

This second experience protocol, while tailored to these participants, included multiple protocol changes (dose, booster availability, no tapering requirement, extended integration), so attributing improvements to any single factor is not possible.

Finally, we note that this study was conducted by investigators with extensive experience in psilocybin therapy and at a retreat center purpose-designed for this work. Whether similar safety and efficacy could be achieved by less experienced teams or in less carefully controlled settings is untested.

This study speaks directly to several priorities articulated in the emerging field of psychedelic public health. First, regarding models of psychedelic care within public health systems, this Group Retreat Psilocybin Therapy model addresses a fundamental barrier to population-level access: the resource intensity of individual treatment. By demonstrating safety with a four-person facilitator team for second experience retreats with 6 and 7 participants—and now with higher doses and individualized booster dosing—this work contributes to developing scalable models that could realistically be integrated into public health infrastructure. The workforce implications are substantial: if equivalent outcomes can be achieved with group models requiring one-quarter the clinician hours per participant, psilocybin therapy becomes far more feasible as a public health intervention for the estimated 25–50% of patients with advanced cancer who experience clinically significant distress.

Second, this study exemplifies the integration of spirituality, ceremony, and public health services. The retreat setting, facilitation model that treats the intervention as a rite of passage, the emphasis on group cohesion and communitas, the use of mystical experience as both outcome and therapeutic mechanism all reflect an approach that honors the ceremonial dimensions of psychedelic healing within a rigorous clinical research framework. The progressive increases in social identification, group cohesion, and communitas scores suggest that the group format may facilitate relational and transpersonal experiences that contribute to therapeutic benefit.

Third, this work offers a critical perspective on medicalization and sustainability. Rather than pursuing ever-more-intensive individualized medical interventions, the group retreat model asks whether healing can emerge from community, shared experience, and mutual support—resources that are inherently renewable rather than scarce (31). The involvement of prior participants as consultants in trial design further reflects a participatory ethos often not seen in medically focused, top-down trial designs. Finally, as a study addressing existential distress in patients with incurable cancer, this work contributes directly to psychedelic applications for cancer-related anxiety, depression, and existential distress, where the need for innovative, accessible approaches is acute.

The data that support the findings of this study are available on request from the corresponding author to qualified researchers but are subject to FDA Certificate of Confidentiality restrictions.