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Analyses the socio-demographic factors associated with health professionals’ completion of the e-learning module and attendance at the two webinars on the End of Life Choice Act 2019 provided by the New Zealand Ministry of Health – Manatū Hauora (MH), and whether completion of the e-learning module and webinars supported health professionals’ understanding of the Act. . Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Aims to determine socio-demographic factors associated with health professionals’ understanding of the End of Life Choice Act, support for assisted dying (AD), and willingness to provide AD in New Zealand. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the therapeutic use of psychedelics at end of life. Much uncertainty remains, however, mainly due to methodological difficulties that beset existing trials. We conducted a scoping review of pipeline clinical trials of psychedelic treatment for depression, anxiety, and existential distress at end of life. Proposed, registered, and ongoing trials were identified from 2 electronic databases (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform). Recent reviews and both commercial and non-profit organization websites were used to identify additional unregistered trials. In total, 25 studies were eligible, including 13 randomized controlled trials and 12 open-label trials. Three trials made attempts beyond randomization to assess expectancy and blinding effectiveness. Investigational drugs included ketamine (  = 11), psilocybin (  = 10), 3,4-methylenedioxymethamphetamine (  = 2), and lysergic acid diethylamide (  = 2). Three trials involved microdosing, and fifteen trials incorporated psychotherapy. A variety of onging or upcoming clinical trials are expected to usefully extend evidence regarding psychedelic-assisted group therapy and microdosing in the end-of-life setting. Still needed are head-to-head comparisons of different psychedelics to identify those best suited to specific indications and clinical populations. More extensive and rigorous studies are also necessary to better control expectancy, confirm therapeutic findings and establish safety data to guide the clinical application of these novel therapies.

Microdosing psychedelic drugs at a level below the threshold to induce hallucinations is an increasingly common lifestyle practice. However, the effects of microdosing on sleep have not been previously reported. Here, we report results from a Phase 1 randomized controlled trial in which 80 healthy adult male volunteers received a 6-week course of either LSD (10 µg) or placebo with doses self-administered every third day. Participants used a commercially available sleep/activity tracker for the duration of the trial. Data from 3231 nights of sleep showed that on the night after microdosing, participants in the LSD group slept an extra 24.3 min per night (95% Confidence Interval 10.3–38.3 min) compared to placebo—with no reductions of sleep observed on the dosing day itself. There were no changes in the proportion of time spent in various sleep stages or in participant physical activity. These results show a clear modification of the physiological sleep requirements in healthy male volunteers who microdose LSD. The clear, clinically significant changes in objective measurements of sleep observed are difficult to explain as a placebo effect. Trial registration: Australian New Zealand Clinical Trials Registry: A randomized, double-blind, placebo-controlled trial of repeated microdoses of lysergic acid diethylamide (LSD) in healthy volunteers; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476 ; ACTRN12621000436875.

Background Major depressive disorder (MDD) is a leading cause of disability worldwide. The current treatments are ineffective in approximately one-third of patients, resulting in a large economic burden and reduced quality of life for a significant proportion of the global population. There is considerable evidence that increased inflammation may distinguish a sub-type of MDD, and there are no validated diagnostic tools or treatments for neuroinflammation in MDD patients. The current study aims to explore the potential role of low-dose naltrexone (LDN), a drug with purported anti-inflammatory properties in the central nervous system, as an adjunctive treatment in patients with MDD. Methods/design This double-blind placebo-controlled hybrid parallel arm study enables the exploration of peripheral and central inflammatory markers with LDN as an approach to investigate inflammation as a pathophysiological contributor to MDD. Eligible participants with MDD ( n = 48) will be stratified into the high and low inflammatory groups according to the levels of high-sensitivity C-reactive protein (hs-CRP) and then randomized to receive LDN or placebo for an initial 12 weeks, followed by a further 12 weeks during which all participants will receive LDN. The primary outcome measure will be the Montgomery-Åsberg Depression Rating Scale (MADRS) administered at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks, 20 weeks, and 24 weeks, to assess the effectiveness of the anti-depressant response. The secondary outcomes include the use of MRI techniques including quantitative magnetization transfer (qMT), echo-planar spectroscopic imaging (EPSI), and diffusion-weighted imaging (DWI) to help to elucidate the neurobiological mechanism of LDN, and the inflammatory mechanisms in action in MDD. Electroencephalography, blood samples, cognitive tasks, and additional questionnaires will also be used to determine if there is a specific profile of symptoms in individuals with inflammatory MDD. Healthy participants ( n = 24) will be recruited for baseline outcome measures only, to enable comparison with patients with MDD. Discussion This trial contributes to the literature on inflammation in MDD, including the understanding of the pathophysiology and efficacy of anti-inflammatory treatments. The investigation of inflammatory mechanisms in MDD is an important first step in the development of biomarkers to classify patient sub-groups, increase the accuracy of diagnosis, and tailor the approach to patients in clinical practice. This study may provide evidence of the benefit of LDN for the groups in whom conventional anti-depressants are ineffective and lead the way for translation into clinical practice. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12622000881730 . Registered on 21 June 2022

Background The global trend of legalising assisted dying (AD) has reshaped end-of-life care practices, and Aotearoa New Zealand’s adoption of the End of Life Choice Act (the Act) in 2019 represents a significant shift. Limited empirical research on AD in New Zealand after the enactment of the Act underscores the need for investigation. Conducting research in the early stages of AD implementation is crucial to building a strong knowledge base and laying the foundation for future research. This would ensure equitable and suitable service provision for the service users. Aim This research captured the experiences of health practitioners directly involved in providing AD under New Zealand’s End of Life Choice Act 2019. Design Using the “memorable case” approach, 22 participants reflected on the process of assessing, treating, and delivering AD services in the first 12 months of implementing the new AD law. Results Thematic analysis identified four major themes underlying the experiences of assisted dying practitioners/providers (ADPs). The themes focused on three aspects of ADPs’ experience: KNOWING: prior personal experience (personal beliefs, clinical background, and AD training) and reflective experiences of DOING assessments, service delivery, and patient/family experiences and BEING an ADP (personal, professional, emotional, and social impacts). Additionally, the themes highlighted the overarching influence of health system infrastructure, challenges, and resources that shaped ADPs’ overall experience. Conclusion These findings contribute to new knowledge by uncovering gaps in understanding, competency, service implementation, and the emotional impact on ADPs. The findings could inform the development of an educational, supportive, and culturally safe program, including resources for workforce development.

Background New Zealand’s End of Life Choice Act 2019 was enacted in 2021, allowing terminally ill people experiencing unbearable suffering to request assisted dying if they are expected to die within six months. Healthcare professionals not directly involved in assisted dying provision may have unique perspectives on implementation, yet this remains under-explored. Methods This qualitative study was conducted between June and November 2022. We used purposive and snowball sampling to recruit potential participants through various sources, including the Ministry of Health’s assisted dying training and communication email list. A multidisciplinary research team developed a semi-structured interview guide. The individual interviews were recorded, transcribed, and thematically analysed to identify core themes. Results Ten healthcare professionals with palliative and primary care backgrounds participated. Five main themes were generated: diverse views on assisted dying; views on the End of Life Choice Act; the interface between palliative care and assisted dying services; education on palliative care and assisted dying; and self-care coping and support. Participants expressed varied attitudes and ethical concerns, with most emphasising the need for reforms in eligibility criteria and improved public understanding. These healthcare professionals provided valuable insights into the broader impact of assisted dying on the healthcare system and the complexities of integrating it with palliative care. Conclusions Integration between palliative care and assisted dying services is crucial for delivering patient-centred care and addressing stigma surrounding end-of-life choices in New Zealand. Adapting international policies around eligibility criteria and safeguards can help streamline the process.

Background: Depressive disorders affect approximately 280 million globally, with many finding treatments ineffective or limited by side effects. Growing evidence suggests that psychedelic therapies may help alleviate depressive symptoms. Among these, lysergic acid diethylamide (LSD) microdosing shows promise for major depressive disorder (MDD). However, research on LSD microdosing in clinical populations remains limited. Objectives: This study aimed to understand the experiences of individuals participating in an open-label trial of LSD microdosing for MDD. Design: Open-label pilot trial in target population (MDD; phase IIa). Methods: Seventeen participants with MDD completed an 8-week LSD microdosing regimen, dosing twice weekly. Following the intervention, participants underwent semi-structured interviews regarding their experiences. Data were analysed using thematic analysis. Results: Themes were grouped into five categories: enhanced self-determination, increased connectedness, improved cognitive processing, better emotional well-being, and negative effects. Conclusion: Reported effects appeared to reinforce one another; that is, self-determination led to feeling more connected, which enhanced cognitive processing and ultimately improved emotional well-being and reduced depressive symptoms. However, this effect was not universal; some individuals reported negative effects or no significant improvement from microdosing LSD. This variability may be due to individual differences in response, insufficient dosage, or the treatment’s lack of effectiveness for some individuals. The presence of side effects highlights the need for a careful titration protocol, while the lack of symptom improvement in some cases reinforces that microdosing is not a guaranteed solution, and expectations should remain realistic. The absence of a placebo control represents a key limitation as it precludes attribution of observed changes specifically to LSD. Trial registration: ANZCTR, ACTRN12623000486628. Registered on 12 May 2023 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385758). Plain language summary Depression affects millions of people worldwide, and many find that current treatments either don’t work or have unwanted side effects. Recent research suggests that psychedelic substances, like LSD, may help improve mood when used carefully small amounts. This practice is known as LSD microdosing. Despite growing interest, there is very little controlled research on how LSD microdosing affects people with depression. In this study, we invited 17 adults with depression to take very low doses of LSD twice a week for eight weeks. After the study, we asked them about their experiences to understand how microdosing affected them. Participants reported a range of experiences. Many described feeling more motivated to engage in daily activities, a stronger sense of connection with others, clearer thinking, new personal insights, and overall improvements in emotional well-being. The improvements participants described often seemed to build on each other—for example, feeling more connected encouraged them to take part in more activities, which then helped them feel mentally clearer and emotionally better. However, not everyone benefited. Some participants reported negative experiences or no noticeable improvement, suggesting that microdosing may not work for everyone. The study also did not include a placebo comparison, so it is unclear whether the changes were due specifically to LSD. Overall, these findings suggest that LSD microdosing may offer some people with depression new ways to feel more connected, motivated, and emotionally balanced. At the same time, careful monitoring is important due to potential side effects, and expectations should remain realistic.