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Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer

Stephen Ross, Gabrielle Agin-Liebes, Sharon L. Lo, Richard J. Zeifman, Leila Ghazal, Julia Benville, Silvia J. Franco-Corso, Christian Bjerre-Real, Jeffrey Guss, Anthony P. Bossis, Sarah E. Mennenga

ACS Pharmacology & Translational Science March 18, 2021 DOI: 10.1021/acsptsci.1c00020 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population People with advanced cancer
Intervention Psilocybin-assisted psychotherapy
Duration 6.5 months post-dosing for suicidal ideation; 4.5-year follow-up for loss of meaning
Topics Psilocybin End-of-life distress Psychedelic-assisted therapy
Keywords Suicide prevention Suicidal ideation Distress Clinical psychology Cancer Depression economics Randomized controlled trial Population Intervention counseling Clinical trial Psychotherapist Poison control Hallucinogen
Citations 133
Key findings Psilocybin-assisted psychotherapy reduced suicidal ideation and loss of meaning in cancer patients with elevated baseline suicidal ideation, with effects persisting up to 4.5 years.

Abstract

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained improvements in depression, demoralization, and hopelessness in people with cancer. Converging epidemiologic and clinical trial findings suggests a potential antisuicidal effect of this treatment. To probe our hypothesis that PAP relieves SI through its beneficial impacts on depression and demoralization (LoM in particular), we performed secondary analyses assessing within- and between-group differences with regard to LoM and an SI composite score. Among participants with elevated SI at baseline, PAP was associated with within-group reductions in SI that were apparent as early as 8 h and persisted for 6.5 months postdosing. PAP also produced large reductions in LoM from baseline that were apparent 2 weeks after treatment and remained significant and robust at the 6.5 month and 3.2 and 4.5 year follow-ups. Exploratory analyses support our hypothesis and suggest that PAP may be an effective antisuicidal intervention following a cancer diagnosis due to its positive impact on hopelessness and demoralization and its effects on meaning-making in particular. These preliminary results implicate psilocybin treatment as a potentially effective alternative to existing antidepressant medications in patients with cancer that are also suicidal, and warrant further investigation in participants with elevated levels of depression and suicidality.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

  • Among participants with elevated baseline suicidal ideation, psilocybin-assisted psychotherapy was associated with within-group reductions in suicidal ideation apparent as early as 8 hours and persisting 6.5 months, plus large reductions in loss of meaning sustained to 4.5 years.

    Synthesized

  • Among participants with elevated suicidal ideation at baseline, psilocybin-assisted psychotherapy was associated with within-group reductions in suicidal ideation as early as 8 hours and persisting 6.5 months, plus large reductions in loss of meaning sustained at 3.2 and 4.5 years.

    Synthesized

Comparable studies

Other randomized controlled trials on end-of-life distress, most cited first.

Study Year Design Participants
PAM trial protocol: a randomised feasibility study of psychedelic microdosing-assisted meaning-centred psychotherapy in advanced stage cancer patients. Māori and non-Māori adults with advanced-stage cancer and symptoms of anxiety and/or... 2024 Randomized controlled trial protocol n = 40
Integrating Immersive Virtual Reality Meditation into Palliative Oncology: A Randomized Trial Protocol for Evaluating Pain Relief and Quality of Life Cancer patients under palliative care at the Pain Therapy and Palliative Care Service... 2026 Randomized clinical trial
Effect of a 5-Minute Mindfulness-of-Gratitude Practice on Suffering and Spiritual Well-Being in Palliative Care Inpatients: A Randomized Controlled Study. Palliative care inpatients 2026 Randomized controlled trial
The effectiveness of reminiscence therapy on the symptom management, the life satisfaction, and the self-transcendence in palliative care patients: a randomized controlled trial. Palliative care patients without cognitive impairment and able to communicate 2024 Randomized controlled trial n = 44

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