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 R Hoeh; Frederick Sundram; Allison J Applebaum; Hineatua Parkinson; Lisa Reynolds

doi:10.1186/s40814-024-01449-9

PAM trial protocol: a randomised feasibility study of psychedelic microdosing-assisted meaning-centred psychotherapy in advanced stage cancer patients

Pilot Feasibility Stud. 2024 Feb 12;10(1):29. doi: 10.1186/s40814-024-01449-9.

Authors

Alesha Wells¹, A P Suresh Muthukumaraswamy², Eva Morunga^{3

4}, Will Evans⁵, Alana Cavadino⁶, Mahima Bansal², Nicola J Lawrence^{7

8}, Amanda Ashley^{8

9}, Nicholas R Hoeh¹⁰, Frederick Sundram¹⁰, Allison J Applebaum¹¹, Hineatua Parkinson¹², Lisa Reynolds¹⁰

Affiliations

¹ Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, 22-30 Park Avenue, Grafton, Auckland, 1023, New Zealand. alesha.wells@auckland.ac.nz.
² School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
³ Cancer Support Service, Te Toka Tumai Auckland, Auckland City Hospital, Te Whatu Ora2 Park Road, Grafton, Auckland, 1023, New Zealand.
⁴ The University of Auckland, 22-30 Park Avenue, Grafton, Auckland, 1023, New Zealand.
⁵ Mana Health, 7 Ruskin Street, Parnell, Auckland, 1052, New Zealand.
⁶ School of Population Health, The University of Auckland, 22-30 Park Avenue, Grafton, Auckland, 1023, New Zealand.
⁷ Department of Oncology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
⁸ Te Pūriri o Te Ora - Regional Cancer and Blood, Te Whatu Ora Te Toka Tumai, 2 Park Road, Grafton, Auckland, 1023, New Zealand.
⁹ Harbour Cancer and Wellness, 212 Wairau Road, Wairau Valley, Auckland, 0627, New Zealand.
¹⁰ Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, 22-30 Park Avenue, Grafton, Auckland, 1023, New Zealand.
¹¹ Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, 641 Lexington Avenue, 7th Floor, New York, NY, 10022, USA.
¹² School of Psychology, University of Auckland, 23 Symonds Street, Auckland Central, 1010, New Zealand.

Abstract

Background: 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.

Methods: 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.

Discussion: 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.

Trial registration: NZCTR, ACTRN12623000478617. Registered 11 May 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385810&isReview=true .

Keywords: Cancer; End-of-life distress; Lysergic acid diethylamide; Meaning-centred psychotherapy; Microdosing; Psychedelics.

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States