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.

Cancer Healthcare Workers' Perceptions toward Psychedelic-Assisted Therapy: A Preliminary Investigation.

Recent clinical trials suggest that psychedelic-assisted therapy is a promising intervention for reducing anxiety and depression and ameliorating existential despair in advanced cancer patients. However, little is known about perceptions toward this treatment from the key gatekeepers to this population. The current study aimed to understand the perceptions of cancer healthcare professionals about the potential use of psychedelic-assisted therapy in advanced cancer patients. Twelve cancer healthcare professionals including doctors, nurses, psychologists and social workers took part in a semi-structured interview which explored their awareness and perceptions toward psychedelic-assisted therapy with advanced cancer patients. Data were analysed using thematic analysis. Four inter-connected themes were identified. Two themes relate to the role and responsibility of being a cancer healthcare worker: (1) 'beneficence: a need to alleviate the suffering of cancer patients' and (2) 'non-maleficence: keeping vulnerable cancer patients safe', and two themes relate specifically to the potential for psychedelic-assisted therapy as (3) 'a transformative approach with the potential for real benefit' but that (4) 'new frontiers can be risky endeavours'. The findings from this study suggest intrigue and openness in cancer healthcare professionals to the idea of utilising psychedelic-assisted therapy with advanced cancer patients. Openness to the concept appeared to be driven by a lack of current effective treatment options and a desire to alleviate suffering. However, acceptance was tempered by concerns around safety and the importance of conducting rigorous, well-designed trials. The results from this study provide a useful basis for engaging with healthcare professionals about future research, trial design and potential clinical applications.

Aberrant white matter microstructure in treatment-resistant schizophrenia✰.

Treatment response in schizophrenia divides into three subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS), and ultra-treatment-resistant schizophrenia (UTRS). White matter abnormalities could drive antipsychotic resistance but little work has investigated differences between TRS and UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were obtained using tract-based spatial statistics. Analysis of variance and post-hoc t-tests were conducted for each measure. Those with TRS had lower FA than healthy controls in superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). No post-hoc tests survived corrections for multiple comparisons and no differences in MD, AD or RD were observed. These data suggest that microstructural deficits in white matter could contribute to TRS but suggest that other mechanisms may be more relevant for UTRS.

Late-Life Suicide in Terminal Cancer: A Rational Act or Underdiagnosed Depression?

CONTEXT: Previous studies have reported significantly elevated standardized mortality rates in older people with cancer. Terminally ill people represent a unique group where suicide may be considered as rational. OBJECTIVES: The aims of this study are to compare the sociodemographic and clinical characteristics of older people with and without terminal cancer who died by suicide and analyze the suicide motives of those with terminal cancer to determine whether they represent rational suicide. METHODS: The New Zealand Coronial Services provided records of all older people (aged 65 years and older) who died by suicide between July 2007 and December 2012. Sociodemographic and clinical data were extracted from the records. Using the characteristics for defining rational suicide, we determined whether the motives in terminal cancer cases represented rational suicide. RESULTS: Of the 214 suicide cases, 23 (10.7%) older people were diagnosed with a terminal cancer. Univariate analysis found that older people with terminal cancer who died by suicide were less likely to have a diagnosis of depression (8.7% vs. 46.6%; P = 0.001) or previous contact with mental health services (4.5% vs. 35.0%; P = 0.004) than those without terminal cancer. About 82.6% of the terminal cancer cases had a motivational basis that would be understandable to uninvolved observers. CONCLUSION: A high proportion of those with terminal cancer had motives suggestive of rational suicide. Future studies are needed to clarify whether the low rate of depression is secondary to underdiagnosis of depression or people with terminal cancer choosing to end their life as a rational act to alleviate suffering.