Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy

Recent clinical trials indicate that one or two high doses of psilocybin, when delivered with psychological support, can produce rapid and clinically meaningful reductions in depression and anxiety among people with life-threatening illness. De La Salle and colleagues note that these trial findings have driven regulatory changes internationally and prompted interest in providing psilocybin-assisted psychotherapy (PAP) outside of research settings. However, compassionate access pathways operate in heterogeneous, less-controlled conditions than clinical trials: formulations (mushrooms versus synthetic psilocybin), dosing, therapist training, preparation/integration procedures, and patient selection can all differ, and the effects of such real-world differences on safety and effectiveness are unknown. This study aimed to fill that gap by prospectively surveying Canadians who received legal, compassionate access to psilocybin via Section 56 exemptions. The investigators sought preliminary longitudinal data on patient characteristics, acute session features, changes in mood, anxiety, quality of life, spiritual well-being and attitudes toward death and medical assistance in dying (MAiD), and to document adverse effects and subjective experiences following a single PAP session in naturalistic settings.

The study used a prospective longitudinal online survey targeting Canadians who had been granted Section 56 exemptions to possess and consume psilocybin-containing mushrooms for distress related to life-threatening illness. Participants registered via an online platform, provided electronic informed consent, and received surveys timed around their planned treatment date. Recruitment occurred December 2021–July 2022 and was conducted via word of mouth and the advocacy group TheraPsil. Of 51 registrants who completed some baseline items, 16 completed the full baseline survey and 10 completed the endpoint; the final analytic sample comprised eight participants who fully completed both baseline and the two-week post-treatment endpoint and whose responses were consistent with known facts about the compassionate access programme. An optional acute post-session survey was sent approximately one day after the session and was completed by five participants. Baseline data collected included demographics, medical and psychiatric history, prior psychedelic use, details of the Section 56 application and costs, social and clinical support, and treatment expectations. The assessment battery, administered at baseline and at two-week endpoint, covered depressive symptoms (PHQ-9, a 9-item questionnaire assessing symptoms over the past 2 weeks), anxiety symptoms (GAD-7), quality of life (McGill QoL-R), spiritual well-being (FACIT-Sp-12), illness symptoms (ESAS-R), attitudes toward MAiD (three bespoke items), death attitudes (DAP-R) and desire for hastened death (SAHD). The optional one-day post-session survey captured session logistics, dosing/form, preparation, therapist characteristics, acute side effects, and three experiential instruments: the Revised Mystical Experience Questionnaire (MEQ30), the Emotional Breakthrough Inventory (EBI), and a brief self-assessment of perceived treatment-related changes. Analyses used descriptive statistics for participant characteristics and paired-sample t-tests to compare baseline versus two-week endpoint scores. Normality was assessed with the Shapiro-Wilk test; for four non-normally distributed variables, Wilcoxon signed-rank tests were performed. The percentage of participants meeting criteria for a 'complete mystical experience' on the MEQ30 was calculated. Analyses were conducted in JASP (v0.17.3) and raincloud plots were generated to visualise individual and group-level distributions.

The final sample included eight individuals (all White; four female), mean age 52.3 years (SD = 10.7). Most lived in British Columbia (7/8) and were English speakers (7/8). All participants reported cancer diagnoses; four were described as palliative and four were in remission. Applications for Section 56 were primarily filed via a non-profit or advocacy group (6/8). Reported out-of-pocket application costs ranged from CAD 300 to 420 for those who paid. Social and healthcare team support was generally rated positively, and most participants expected at least minor-to-major improvements across psychological domains prior to treatment. Substance use histories varied: most had prior use of classic psychedelics (psilocybin 6/8, LSD 5/8) though most had not regularly used such substances in the month prior. Psychiatric histories included anxiety disorders (3/8), major depressive disorder (1/8), post-traumatic stress disorder (1/8) and anticipatory grief (1/8); half reported no psychiatric history. Comparing baseline to the two-week endpoint, paired analyses showed statistically significant reductions in anxiety (GAD-7 and ESAS-R anxiety items) and in depressive symptoms as measured by the ESAS-R. There were also significant decreases in pain and fear of COVID-19, and significant increases in overall quality of life and psychological QoL (McGill QoL-R), plus increases in total and Peace subscale scores of spiritual well-being (FACIT-Sp-12). PHQ-9 scores did not show a significant change, which the authors suggest may reflect a floor or basement effect. The paper noted over 50% reductions on GAD-7 for some participants but did not present complete effect-size tables in the extracted text. Five participants completed the one-day post-session survey. All consumed dried psilocybin mushrooms or truffles (reported dose range 2.5 g [n = 1] to 5 g [n = 4]; one participant received two close doses totalling ~3.33 and 1.66 doses). Two took them whole and three prepared them as food/tea. Preparation involved counselling sessions (mean ~3 sessions, ~5.8 hours total). Therapists present included registered nurses, physicians, counsellors and psychologists; most therapists were reported to have personal experience with psychedelics and sessions were commonly conducted in group settings with multiple facilitators. Acute side effects reported one day post-session (n = 5) most frequently included nausea/vomiting (4/5), crying (3/5), headache (3/5) and sweat/chills (3/5). Experiential measures showed a mean MEQ30 total score of 64.3 (± 23.6), with 2/5 participants meeting criteria for a 'complete mystical experience' (≥ 60% on each factor). Mean EBI total was 63.4 (± 27.7), with the highest endorsed EBI item being having faced difficult emotions (mean ~89.2). Subjective meaningfulness varied: some participants described the session as among the most meaningful or spiritually significant of their lives, while all reported some degree of psychological challenge. Notably, one participant reported substantial worsening across depression, fear of death, spiritual well-being and relationships at the endpoint. Two participants reported serious safety concerns in open responses as noted in the Discussion.

De La Salle and colleagues interpret these preliminary real-world data as broadly consistent with controlled clinical trials showing that psilocybin-assisted therapy can reduce anxiety and some depressive symptoms, and can enhance quality of life and spiritual well-being among people with cancer-related distress. The authors highlight that several patternsof change (e.g. reductions in anxiety, improvements in QoL and FACIT-Sp scores, and MEQ30/EBI findings) resemble those reported in prior randomised trials and meta-analyses. At the same time, the investigators emphasise important safety and implementation concerns unique to compassionate-access settings. Unlike clinical trials, participants in this sample consumed natural psilocybin-containing mushrooms rather than standardised synthetic formulations, were treated in heterogeneous settings, and experienced variable therapist preparation and oversight. Two participants reported serious safety concerns and one experienced marked worsening across several psychological domains, leading the authors to warn that unstandardised compassionate-access programmes may carry risks exceeding those observed in controlled research. They argue that risks could stem from variable therapist training, absence of standardised screening and safety monitoring, and looser inclusion criteria than in trials. The authors note further observations: participants entered treatment with high expectations of benefit, which may bias reported outcomes; improvements in spiritual well-being did not translate into changes in attitudes toward death or likelihood of pursuing MAiD within the two-week follow-up; and common side effects (nausea, headache, crying) mirror adverse events reported in clinical trials. Given these mixed findings, the study team recommends implementing formal surveillance and data-collection systems for compassionate-access PAP, such as central registries, minimum anonymised datasets and networks of providers to standardise care and enable research integration. Key limitations acknowledged by the authors include the small and demographically homogenous sample, recruitment challenges and likely selection biases, the anonymous and self-reported nature of the data, the open-label and non-standardised treatments, limited acute physiological monitoring, and lack of detailed data on prior ceremonial use or microdosing. The authors call for larger, systematic real-world evaluations that adopt the rigorous psychological support and risk-assessment standards used in clinical trials, and for attention to scalability and sustainable funding models if PAP is to be widely implemented.

This preliminary longitudinal survey provides one of the first descriptive accounts of Canadians who received compassionate access to psilocybin-assisted psychotherapy for distress associated with life-threatening illness. Decreases in anxiety and some measures of depressive symptoms, and increases in quality of life and spiritual well-being were observed two weeks after a single session for most participants, but heterogeneity in experiences—including one marked negative outcome and reports of safety concerns—underscores potential risks in unregulated real-world delivery. The authors conclude that compassionate-access programmes would benefit from formal surveillance, standardised psychological support and outcome monitoring, and coordinated provider networks to improve safety and to inform future policy and clinical practice as legal access expands.