PAM trial protocol: a randomised feasibility study of psychedelic microdosing-assisted meaning-centred psychotherapy in advanced stage cancer patients.
Alesha Wells, A P Suresh Muthukumaraswamy, Eva Morunga, Will Evans, Alana Cavadino, Mahima Bansal, Nicola J Lawrence, Amanda Ashley, Nicholas Hoeh, Frederick Sundram, Allison J Applebaum, Hineatua Parkinson, Lisa Reynolds
Pilot and Feasibility Studies February 12, 2024 DOI: 10.1186/s40814-024-01449-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial protocol Double-blind Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Māori and non-Māori adults with advanced-stage cancer and symptoms of anxiety and/or depression |
| Interventions | LSD microdose meaning-centred psychotherapy |
| Dose | 4-20 µg |
| Duration | 7 sessions of psychotherapy with 13 doses; follow-up at 1 month and 6 months |
| Topics | End-of-life distress LSD Microdosing Psychedelic-assisted therapy |
| Keywords | Meaning-centred psychotherapy Terminal care Psychedelics-therapy psychedelic therapy Hallucinogen therapy End-of-life-care palliative care Hospice care Cancer-mental-health |
| Citations | 10 |
| Key findings | The study will evaluate whether adding an LSD microdose to meaning-centred psychotherapy is feasible, acceptable, and safe for advanced cancer patients with psychological distress. |
Abstract
An advanced cancer diagnosis can be associated with a significant profile of distress. Psychedelic compounds have shown clinically significant effects in the treatment of psychological distress in patients with advanced-stage cancer. Given the challenges of delivering timely and effective intervention in the advanced cancer context, it is possible that an alternative, more pragmatic, approach lies in psychedelic 'microdosing'. Microdosing refers to repeated administration of psychedelics in sub-hallucinogenic doses. The purpose of this study is to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing psychedelic microdose-assisted-meaning-centred psychotherapy (PA-MCP) to standard meaning-centred psychotherapy (MCP) in New Zealand indigenous (Māori) and non-indigenous people with advanced cancer and symptoms of anxiety and/or depression. Although MCP is a well-established psychotherapeutic treatment in advanced cancer populations, the potential efficacy and effectiveness of this therapy when delivered alongside a standardised microdose regimen of a psychedelic compound have not been investigated. Participants with advanced-stage cancer and symptoms of anxiety and/or depression (N = 40; 20 Māori, 20 non-Māori) will be randomised under double-blind conditions to receive 7 sessions of MCP alongside 13 doses of either an LSD microdose (4-20 µg) (PA-MCP) or inactive placebo (placebo-MCP). The feasibility, acceptability, and safety of this intervention and physiological and psychological measures will be recorded at baseline, at each session of MCP, and at a 1-month and 6-month follow-up. Our findings will evaluate the feasibility, acceptability, and safety of a larger randomised controlled trial and provide an initial indication of the potential benefits of psychedelic microdosing for psychological distress in advanced-stage indigenous and non-indigenous cancer patients. NZCTR, ACTRN12623000478617. Registered 11 May 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385810&isReview=true .
Comparable studies
Other randomized controlled trials on LSD and microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity. Healthy young adults, 18 to 35 years old | 2019 | Randomized controlled trial | n = 20 |
| Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Healthy male volunteers | 2023 | Randomized controlled trial | n = 80 |
| Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity. Healthy adults | 2023 | Within-subject, double-blind, placebo-controlled experiment | n = 18 |
| Greater subjective effects of a low dose of LSD in participants with depressed mood. Adults with mild depressed mood (scoring high or low on the Beck Depression-II inventory) | 2024 | Randomized controlled trial | n = 39 |
| Inter-individual variability in neural response to low doses of LSD. Healthy participants | 2024 | Randomized controlled trial | n = 53 |
Citations in the library
Cited by 9
- Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review. Medicina (Kaunas, Lithuania) March 21, 2025
- Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon Cancers April 27, 2024
- LSD: Mechanisms and relevance to the treatment of depression Neuroscience & Biobehavioral Reviews October 10, 2025
- The effect of psychedelic microdosing on animal behavior: A review with recommendations for the field Neuroscience & Biobehavioral Reviews May 9, 2025
- A Rapid Review of Psychedelic-Assisted Therapy in the Context of Palliative Care. Journal of Hospice and Palliative Nursing April 1, 2025
and 4 more in the library
Cites 31
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases The Journal of Nervous and Mental Disease March 4, 2014
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
and 26 more in the library