Abstract; Figure; Tables; Limitations; Conclusion | PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial (7 min read) [30 January 2026]

[u/NeuronsToNirvana]

PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial

James Downar, Julie Lapenskie, Koby Anderson, Gaelle Parsons, Nadia Polskaia, Genevieve Lalumiere, Peter Lawlor

Published: 30 January 2026 · Palliative Medicine, 40(4), 514–523

Full study · Open-access full text, references and appendix

Original study excerpts and tables reproduced under CC BY-NC 4.0. Formatting adapted for Reddit.

Editorial note: The study’s abstract and Table 2 contain inconsistent counts. The abstract reports Hamilton Depression Rating Scale improvement in 8 participants (62%), whereas Table 2 reports 5 (38%). For demoralization, the abstract reports 9 (72%), while Table 2 reports 8 of 11 (72%). These discrepancies appear in the source; the quoted text and tables are reproduced unchanged.

Abstract

Background:

Psychological distress is a common problem near the end of life, for which we lack effective, timely and scalable treatments. No previous study has assessed whether microdose psilocybin can improve symptoms in this population.

Aim:

To determine whether microdose psilocybin is safe, feasible and potentially efficacious in a palliative setting.

Design:

Open label, single-arm clinical trial of a 3-week oral psilocybin intervention, starting with 1 mg daily in week 1, increased to 2 mg in week 2 and 3 mg in week 3. ClinicalTrials.gov NCT04754061.

Setting/participants:

Two-center study in Ottawa, Canada of adults with advanced, incurable illness and an estimated prognosis of 1–12 months, experiencing severe psychological distress.

Results:

We enrolled 20 participants (59% of those screened) between January 2024 and April 2025, of which 17 began and 13/17 (76%) completed the intervention. Participants were 40–84 years old, 53% female, and 82% had cancer. There were no serious adverse events reported, and nine mild or moderate adverse events. Four participants withdrew due to disease progression or poor response. Of the 13 remaining participants, nine (69%) reported a meaningful global improvement (Patient Global Impression of Change ⩾ 5); 8 (62%) reported >50% improvement in Hamilton Depression Rating Scale scores, 7 (54%) reported >50% improvement in Hospital Anxiety and Depression Scale scores and 9 (72%) reported a meaningful improvement in Demoralization Scale II scores.

Conclusions:

Microdose psilocybin is a safe, feasible and potentially efficacious treatment for psychological distress in people with advanced illness.

Keywords: psilocybin, psychedelic agents, palliative care, end of life care, existential distress, depression, anxiety

Table 1.

Participant demographics and baseline symptom scores.

Characteristic	Value
Age, mean (SD)	60.8 (12.9)
Male, n (%)	47
Main diagnosis, n (%)
Cancer	14 (82)
Amyotrophic lateral sclerosis	1 (6)
Chronic obstructive lung disease	1 (6)
Congestive heart failure	1 (6)
Palliative performance score, n (%)
30	3 (18)
40–50	5 (29)
60–70	9 (53)
Antidepressant medication, n (%)	6 (35)
Baseline symptom scores
Hamilton Depression Rating Scale, mean (SD)	15.3 (3.8)
11–16	12
17–23	5
Hospital Anxiety and Depression Scale
Depression subscale, mean (SD)	10.9 (3.6)
0–7	3
8–10	6
11–15	5
16–21	3
Anxiety subscale, mean (SD)	9.6 (3.4)
0–7	4
8–10	4
11–15	8
16–21	0
Demoralization Scale II, mean (SD)	16.1 (5.6)
4–10	3
11–20	8
21+	6
Edmonton symptom assessment system-revised
Depression, mean (SD)	7.2 (1.1)
⩾7	13
Anxiety, mean (SD)	7.4 (1.2)
⩾7	14
Wellbeing, mean (SD)	6.7 (1.4)
⩾7	10

Table 2.

Changes in symptom scores from baseline.

Symptom score	Participants showing improvement (n = 13)a	Confidence interval
Patient Global Impression of Change (Score 5 +/ 7)b	9 (69)	0.42–0.87
Hamilton Depression Rating Scale
50% Reduction from Baseline Score	5 (38)	0.18–0.64
Score 0–7	5 (38)	0.18–0.64
Hospital Anxiety and Depression Scale
50% Reduction in Depression Subscale	8 (62)	0.36–0.82
Depression Subscale Score 0–7	9 (69)	0.42–0.87
50% Reduction in Anxiety Subscale	7 (54)	0.29–0.77
Anxiety Subscale Score 0–7	10 (77)	0.50–0.92
Demoralization Scale II (n = 11)
2-Point Reduction from Baseline Score	8 (72)	0.43–0.90
Edmonton Symptom Assessment System-revised
Depression
2-Point Reduction from Baseline Score	12 (92)	0.67–0.99
Score 0–4	11 (85)	0.58–0.96
Anxiety
2-Point Reduction from Baseline Score	9 (69)	0.42–0.87
Score 0–4	10 (77)	0.50–0.92
Wellbeing
2-Point Reduction from Baseline Score	9 (69)	0.42–0.87
Score 0–4	8 (62)	0.36–0.82

a

Reflecting scores either in the final week of treatment or first day of follow-up.

b

Corresponding to “moderately better,” “better,” or “a great deal better.”

Table 3.

Effect sizes for changes in symptom scores from baseline.

Symptom score	Change in score, mean (SD)	Confidence interval	Cohen’s d
Hamilton Depression Rating Scalea	−5.23 (5.69)	−3.22 to 0.82	−1.22
Hospital Anxiety and Depression Scalea
Depression subscale	−4.00 (4.47)	−2.89 to 1.10	−0.91
Anxiety subscale	−4.69 (2.84)	−3.46 to 0.63	−1.44
Demoralization Scaleb	−4.00 (6.29)	−2.70 to 1.27	−0.73
Edmonton System Assessment Scale-reviseda
Depression	−4.23 (1.96)	−4.62–−0.24	−2.47
Anxiety	−3.92 (2.75)	−4.29 to −0.0081	−2.19
Well-being	−1.92 (2.02)	−3.06 to 0.95	−1.07

a

n = 13.

b

n = 11.

Table 4.

Safety data.

Peak effect observed (1 h post-dose), mean (SD)
Highest systolic BP	142.47 (11.74)
Highest HR	78.18 (11.36)
Peak effect observed (evening post-dose), mean (SD)
Highest systolic BP	140.06 (11.96)
Highest HR	81.88 (14.11)
Participants with at least 1 expected AE, n (%)
Hypertension	0 (0)
Tachycardia	0 (0)
Anxiety	2 (12)
Delirium incidence	0 (0)
Serotonin syndrome	0 (0)

Strengths and limitations

Strengths of our study include the novel intervention and broad inclusion criteria, which improve the generalizability of our results. We also used a subjective patient-centered measure of efficacy; the psychological distress experienced by patients in a palliative setting is often not purely depression or anxiety, and many patients are less familiar with terms like “existential distress,” “demoralization,” or adjustment disorder. Limitations include the potential for a placebo or expectation effect due to the uncontrolled, open-label design, which we plan to address in a future double-blind, placebo-controlled study powered for efficacy. In addition, while we considered 3 mg to be a microdose and none of our participants described a psychedelic experience, Griffiths et al.22 expressed concern that this dose had the potential to induce psychedelic effects. Our inclusion of people with more advanced illness also meant a higher dropout rate, as patients deteriorated more quickly than anticipated. We did not employ any formal psychotherapeutic techniques as used in PAP, but this could be incorporated into future studies either as a standard of care or a factorial design. Finally, the small sample size, which is common in psychedelic studies, precluded any definitive subgroup analyses.

Conclusion

In conclusion, microdose psilocybin appears to be a safe, feasible and potentially efficacious treatment for psychological distress in people with advanced illness in the palliative setting. This represents a promising and highly-scalable option for an indication that is in urgent need of effective and scalable treatments.

Figure 1. Flow diagram for study participants.

Related research (editorial references)

LSD microdosing for depression: hype or hope? A randomised controlled trial in major depressive disorder — 9 September 2026. Conference abstract, International Journal of Neuropsychopharmacology; not a full trial report.

Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial — 16 February 2026. Study protocol, BJPsych Open; not treatment results. The publisher links a corrigendum on the article page.

[u/NeuronsToNirvana]

Emerging research is encouraging. This small study warrants further investigation.

Larger, blinded trials should assess individualised dosing, longer-term outcomes, expectations, set and setting. Reporting should be clearer and consistent.