Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

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

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 (Maori) 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 Maori, 20 non-Maori) 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 .

The perceptions of cancer health-care practitioners in New Zealand and the USA toward psychedelic-assisted therapy with cancer patients: A cross-sectional survey.

OBJECTIVES: A resurgence of research investigating the administration of psychedelic compounds alongside psychotherapy suggests that this treatment is a promising intervention for anxiety, depression, and existential distress in people with cancer. However, psychedelic treatment that induces a mind-altering experience potentially poses barriers to vulnerable cancer patients, and health-care practitioners may have concerns about referring their patients to trials investigating this approach. The aim of the current study was to investigate the perceptions of cancer health-care practitioners based in New Zealand and the USA related to psychedelic-assisted therapy. METHODS: This study utilized a cross-sectional survey of cancer health-care practitioners in New Zealand and the USA via convenience sampling to identify their perceptions about the concept of conducting psychedelic-assisted therapy with cancer patients. RESULTS: Participants perceived that (1) psychedelic-assisted therapy has the potential to provide benefit for cancer patients, (2) research in this area across a variety of domains is important, (3) work should consider spiritual and indigenous perspectives of health, and (4) there was willingness to refer patients to trials in this area, especially patients with advanced disease who were no longer going through curative treatment. Participants in the USA had greater awareness of psychedelics than the New Zealand sample; however, New Zealand participants more strongly believed that spiritual/indigenous factors should be considered in psychedelic-assisted therapy. SIGNIFICANCE OF RESULTS: Cancer health-care practitioners in our sample considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts.