This double-blind placebo-controlled trial (n=35) found that psilocybin-assisted psychotherapy (25mg) significantly reduced depression and anxiety symptoms in adults with life-threatening illnesses compared to an active placebo (100mg niacin), with benefits sustained at 26 weeks and improvements in spiritual well-being, quality of life, demoralisation, and death anxiety.
Abstract of Psilocybin-assisted psychotherapy for depression and anxiety associated with life threatening illness
“Importance Psilocybin-assisted psychotherapy may offer a novel approach to treating depression, anxiety, and existential distress in individuals with life threatening illnesses, where current treatments show limited efficacy.
Objective To evaluate the efficacy and safety of psilocybin-assisted psychotherapy versus active placebo and psychotherapy in adults with life-threatening illnesses.
Design Double-blind, randomized controlled phase 2b trial (RCT) with an open-label extension and 6-month follow-up (January 2020 – October 2023).
Setting Single-site study at a tertiary hospital’s palliative care department (St. Vincent’s Hospital Melbourne affiliated with the University of Melbourne).
Participants Adults aged 18–80 with a life-threatening illness and clinically significant depression and/or anxiety.
Interventions Participants were randomized to receive 25 mg psilocybin or 100 mg niacin (active placebo), alongside three preparatory psychotherapy and six post-dose integration psychotherapy sessions. After 6–7 weeks post double blind dose, all participants received 25 mg psilocybin in an open-label extension, enabling a two dose versus one dose group comparator. Participants were followed up to 26 weeks post open label dose.
Main outcomes and measures Primary outcome was change in depression and anxiety symptoms, assessed using the Hospital Anxiety and Depression Scale (HADS), from baseline to 6–7 weeks post-dose. Key secondary outcomes included the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory – State version (STAI-S), which provided complementary, dimensional measures of depression and anxiety over the same time period. Additional secondary outcomes included Death Attitudes Profile, WHOQOL-BREF, State-Trait Anxiety Inventory (STAI-Trait scale), Mystical Experiences Questionnaire, and Persisting Effects Questionnaire. Exploratory outcomes included spiritual well-being, hopelessness, demoralization, and HADS-Trait scores.
Results Thirty-five participants (mean age 56.0; 54.3 % female) were randomized (psilocybin: n = 17; placebo: n = 18). At 6–7 weeks, psilocybin produced significantly greater reductions in HADS depression (B = –2.49; P = .02; d = 1.12), BDI-II (B = –7.56; P = .004; d = 2.97), and STAI-State anxiety (B = –12.59; P = .005; d = 4.51) compared to placebo. Benefits were sustained at 26 weeks. Exploratory outcomes demonstrated enhanced spiritual well-being, quality of life, and significant reductions in demoralization, death anxiety and hopelessness. No serious treatment-emergent adverse events occurred. Psilocybin was associated with more mild-to-moderate adverse events. One participant withdrew due to anxiety during dosing.
Conclusions and relevance Psilocybin-assisted psychotherapy appears safe and may offer durable relief from depression and anxiety in individuals with a life-threatening illness.“
Authors: Margaret L. Ross, Ravi Iyer, Martin L. Williams, Mark Boughey, Clare O’Callaghan, Richard Hiscock & Justin Dwyer
Summary of Psilocybin-assisted psychotherapy for depression and anxiety associated with life threatening illness
Ross and colleagues report a single-site, Phase IIb randomised, double-blind, active-placebo-controlled trial evaluating psilocybin-assisted psychotherapy for depression and anxiety in people living with a life-threatening illness. The study builds on earlier research in cancer populations by explicitly including both malignant (e.g., metastatic cancers) and non-malignant advanced diseases (e.g., motor neurone disease/ALS, advanced cardiac failure). The authors position existential distress—fear of death, demoralisation, and spiritual suffering—as tightly linked to anxiety and depression, and as drivers of poorer quality of life and more difficult symptom control. Existing treatments (psychological therapies, antidepressants, and sedatives) have modest or inconsistent effects in this group and may introduce drawbacks such as tolerance, delirium, or sedation. Psilocybin, delivered within a structured psychotherapy framework, is presented as a candidate intervention capable of producing rapid and durable reductions in distress while enhancing spiritual well-being.
The study’s primary objective was to test whether a single psilocybin session plus psychotherapy outperformed an active placebo (niacin) plus the same psychotherapy on validated measures of depression and anxiety over six to seven weeks. Secondary objectives extended to quality of life, attitudes towards death, and the character of the acute experience; exploratory objectives included hopelessness, demoralisation, and spiritual well-being. The trial also incorporated an open-label extension in which all participants received psilocybin, allowing comparison of one versus two psilocybin doses and assessment of durability to 26 weeks.
Find this paper
https://doi.org/10.1016/j.genhosppsych.2025.08.001
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Cite this paper (APA)
Ross, M. L., Iyer, R., Williams, M. L., Boughey, M., O'Callaghan, C., Hiscock, R., & Dwyer, J. (2025). Psilocybin-assisted psychotherapy for depression and anxiety associated with life threatening illness: A phase 2b randomized controlled trial. General Hospital Psychiatry.
Study details
Compounds studied
Psilocybin
Topics studied
Depression
Anxiety
Palliative Care
Study characteristics
Original
Placebo-Controlled
Double-Blind
Open-Label
Longitudinal
Randomized
Follow-up
Participants
35
Humans
Compound Details
The psychedelics given at which dose and how many times
Psilocybin 25 mg | 1xLinked Clinical Trial
Psilocybin-assisted psychotherapy for the treatment of depression and anxiety associated with life-threatening illnessThis parallel-group, double-blinded, randomised controlled trial (n=35) investigates the use of psilocybin (25mg), combined with psychotherapy, for managing depression and anxiety in terminally ill patients.