INTRODUCTION:Despite growing interest in microdosed psychedelics, clinical trial evidence remains limited. We present daily mood, subjective perception of effects, and pharmacokinetics from an 8-week regimen of microdosed lysergic acid diethylamide (LSD) as a treatment for major depressive disorder in an open-label trial in which participants reported a mean symptom reduction of 60%. METHODS:Participants took 16 sublingual LSD doses: 8 μg onsite, with bloods collected at eight time-points, then twice weekly at home with titration (6-20 μg). Pharmacokinetic parameters were estimated using non-compartmental and compartmental modelling. Daily questionnaires were used to assess depression severity with the self-reported Hamilton Depression Rating Scale (HAMD6), and mood with visual analogue scales (VAS). Drug effects were recorded with VAS scales on each dosing day. Linear mixed models were used to compare dosing days to one- and two-day post-dosing, and to identify linear trends (tolerance/sensitisation) of drug effects. RESULTS:Nineteen participants (males n = 15, 79%) received the intervention. Daily VAS indicated increased scores of mood-related states (e.g., more creative, happier) on dosing days (p = 0.009 to 0.039), but not in depression (p = 0.291). There was no indication of tolerance or sensitisation (p > 0.081). Non-compartmental AUC0-tlast was 836 ± 319 pg.h/mL, Cmax 212 ± 77.7 pg/mL and Tmax 1.17 ± 0.56 h. DISCUSSION:Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. It provides the pharmacokinetic parameters of 8 μg of LSD in a sample of people with depression and indicates no tolerance or sensitisation to repeated microdoses of LSD, despite incremental dose titration.

Major depressive disorder (MDD) affects approximately 5 % of the global population. Classic psychedelics have shown promise in treating various mental health disorders. This study evaluated the feasibility and tolerability of an 8-week regimen of microdosed lysergic acid diethylamide (LSD) as a treatment for major depressive disorder in an open-label phase 2A trial (LSDDEP1). Nineteen participants (15 male), most of whom were taking an antidepressant medication (n = 15), took 16 doses of LSD (8 μg initially, then 6-20 μg twice weekly at home), with the first dose administered in the clinic. We assessed tolerability through withdrawal rates due to adverse events and feasibility by clinic visit attendance. Safety measures included adverse events, blood laboratory tests, electrocardiography (ECG), and echocardiography. Depression was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). No serious or severe adverse events and clinical alterations in safety measures were observed, being this the first study to evaluate valvulopathy after repeated psychedelic administration in humans. One participant withdrew due to experiencing anxiety when dosing; all scheduled clinic visits were attended. MADRS scores were reduced by 59.5 % at the end of the intervention and were sustained for up to six months. Improvements were also noted in anxiety, rumination, stress, and quality of life. While limited by an open-label design and small sample size, this study provides preliminary evidence supporting the safety and feasibility of treating moderate depression with microdosed LSD and underscores a need for further randomised controlled trials. Trial registration: ANZCTR, ACTRN12623000486628 (12 May 2023).

The severity and impact of dry mouth in patients receiving palliative care is underreported, and assessment methods for this condition are lacking consensus. This study aimed to examine the severity of dry mouth in a palliative population as rated on a visual oral dryness scale and to compare these findings with the actual symptoms experienced by patients, as reported through both a symptom scale measure and a bother questionnaire. 40 participants took part in this cross-sectional study. The results indicated that xerostomia is a significant and debilitating symptom for many patients receiving palliative care. Daily activities such as speaking and sleeping were rated as highly affected by xerostomia, whereas swallowing was not reported to be as badly affected. The use of the oral dryness scale as an assessment technique in this population showed correlation with some, but not all, of xerostomia-related symptoms experienced by participants.

Background The prevalence of dry mouth in the palliative care population is well documented and increases due to polypharmacy, radiotherapy and systemic conditions. Saliva as a lubricant for the mouth and throat has implications for swallowing, chewing, and speech. The literature about the experience of xerostomia (perceived feeling of dry mouth) in palliative care is scarce. Clinical evidence suggests that xerostomia has a negative impact on people’s comfort, however, no recent studies explored this impact in detail. This new knowledge is paramount to adhere to the principles of palliative care. Aims To evaluate the impact of xerostomia on the lives of people receiving palliative care with particular reference to eating and speaking. Design A qualitative descriptive study (interview design). Thematic analysis was used for data analysis. Setting A single specialist palliative care centre in Ireland. Results The majority of participants (35/40) had cancer. Xerostomia was reported to have multiple physical, psychological, and daily life consequences. Participants provided insights into the impact of xerostomia on sleeping, eating, talking, denture wearing, and they described in detail their intra-oral sensations associated with xerostomia. The negative effect of xerostomia on speech was reported as the most significant to participants. Conclusion Xerostomia has a profound impact on the daily lives of people receiving palliative care, including physical and psychological consequences. Speaking is often affected, which can impede the person’s ability to communicate. There needs to be increased awareness of the impact of xerostomia and more research is required to understand how best to manage xerostomia in a palliative care setting.

Microdosing psychedelics is an increasingly popular phenomenon where small amounts of psychedelic drugs are taken regularly. Qualitative data have been published regarding the experiences of microdosers, but never in the context of a randomised controlled trial. Semi-structured video interviews with 40 healthy males were conducted following a double-blind placebo-controlled trial of 10 µg of lysergic acid diethylamide every third day for 6 weeks. Data were analysed using content analysis with initial deductive categories derived from the literature populated with inductively derived codes. Drug effects were classified in the following categories: “emotions and mood,” “social life,” “mindfulness,” “cognition, work, and creativity,” and “physiological effects,” with an additional “influences” code for non-drug modifiers of participants experiences in the trial. Themes which spanned these categories were openness to experiences and a bidirectionality of effects. Some identified codes have potential clinical relevance and may support the use of microdosing in treatment of mood disorders. Reports of changes in anxiety suggest important considerations in selecting appropriate patients and doses. Of relevance to psychedelic clinical trial design are participants’ reports regarding set and setting, the uncertainty caused by participating in a placebo-controlled trial, and perceived bidirectionality of effects.

Expectations can impact antidepressant treatment and psychedelic therapy, often enhancing placebo effects and influencing outcomes. However, research in this context is lacking. Our study explored the expectations of participants with major depressive disorder (MDD) before microdosing lysergic acid diethylamide (LSD) in an open-label trial. Twenty-three individuals with MDD completed a semi-structured interview about their expectations before commencing an LSD microdosing regimen. Interviews were transcribed and analysed using qualitative content analysis and compared with Credibility/Expectancy Questionnaire scores. Response categories were motivation, influence, expected effects, expected mechanisms, and hope. Over half of the participants (16/23 participants) cited previous treatment failure as a motivation for participating, with additional motivations including long-term depression (7/23), interest in psychedelics (9/23), desire for microdosing to be available to others (4/23) and recommendation by a professional (2/23). Media (12/23) and friends/family (5/23) were major influences on microdosing opinions, as was the desire to avoid influence (10/23). Participants expected various effects, including changes to consciousness (5/23), subtle effects (10/23) or had no expectations (12/23). Some participants were unsure about mechanisms (7/23), but others believed microdosing might cause neural rewiring (11/23) or changes to thought patterns (7/23). Participants were optimistic (8/23), cautious (11/23), and/or excited about the research (7/23). Our study highlights the role of media in shaping expectations and the extent to which participants expect healing through psychedelics. Hope acted as a motivator and a disappointment buffer. Future research should develop a psychedelic-specific expectancy measure covering additional factors not covered by current measures.

Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo. This is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 μg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures. This study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants’ naturalistic environment. The measures included are designed to assess the drug’s safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials. ANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024.

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.

OBJECTIVESA 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.METHODSThis 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.RESULTSParticipants 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 RESULTSCancer 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.

BACKGROUND:Microdosing psychedelic drugs is a widespread social phenomenon with diverse benefits claimed for mood and cognition. Randomized controlled trials have failed to support these claims, but the laboratory-based dosing in trials conducted to date may have limited ecological validity. METHODS:Healthy male volunteers were randomized into lysergic acid diethylamide (LSD) (n = 40) and placebo (n = 40) groups and received 14 doses of either 10 μg LSD or an inactive placebo every 3 days for 6 weeks. First doses were given in a supervised laboratory setting, with other doses self-administered in a naturalistic setting. Results of safety data, blinding, daily questionnaires, expectancy, and pre-/postintervention psychometrics and cognitive tasks are presented here. RESULTS:The most notable reported adverse event was treatment-related anxiety, which prompted the withdrawal of 4 participants from the LSD group. Daily questionnaires showed credible evidence (>99% posterior probability) of improved ratings of creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, and these effects remained when controlling for preintervention expectancy. No questionnaire or cognitive task showed a credible change between baseline and 6-week assessment time points. CONCLUSIONS:Microdosing LSD appears to be relatively safe in healthy adult men, notwithstanding a risk of anxiety. While microdosing elicited transient increases in scales associated with mood-elevating effects, it was not sufficient to promote enduring changes to overall mood or cognition in healthy adults. Future microdosing trials in clinical populations will require the use of active placebos to control for placebo effects and dose titration to adjust for interindividual variability in drug response.

Background Globally, an estimated 260 million people suffer from depression [1], and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments [2], a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin [3]. Beyond anecdotal reports from those who self-medicate in this way, few clinical trials have evaluated this practice. In our recently published phase 1 study in healthy volunteers [4], we determined that LSD microdosing was relatively safe and well tolerated in that cohort. Furthermore, the data demonstrated that conducting such microdosing trials is broadly feasible, with excellent adherence and compliance to the regimen observed. In this open-label pilot trial of patients with major depressive disorder (LSDDEP1), we will test the tolerability and feasibility of an 8-week regimen of LSD microdosing in this patient group prior to a larger subsequent randomised controlled trial (LSDDEP2). Methods Twenty patients meeting the DSM-5 criteria for major depressive disorder will receive an 8-week LSD microdosing treatment regimen. The treatment protocol will use a sublingual formulation of LSD (MB-22001) delivered twice per week under a titration schedule using a dose of 5–15 µg. Tolerability will be assessed by quantifying the percentage of participants who withdraw from the trial due to adverse events attributable to the treatment regimen, while feasibility will be assessed by quantifying the percentage of attended clinic visits once enrolled. To determine whether there is any antidepressant response to the LSD microdosing regimen, MADRS scores will be assessed at baseline and 2, 4, 6, and 8 weeks after the commencement of the regimen. Discussion The results of LSDDEP1 will provide valuable information regarding the tolerability and feasibility of a proposed LSD microdosing regimen in patients with MDD. Such information is critically important to optimise trial design prior to commencing a subsequent and more resource-intensive randomised controlled trial. Trial registration ANZCTR, ACTRN12623000486628. Registered on 12 May 2023.

This systematic review aimed to explore the impact educational interventions have on undergraduate nursing and medical students' attitudes and empathy levels towards people with disability. There are over one billion people with some form of disability currently. A growing body of research reveals that nurses and doctors display negative attitudes including decreased empathy towards people with disability. A systematic review using narrative synthesis of chosen randomized controlled trials was employed. A comprehensive search was completed in June 2021 on six databases (CINAHL, Medline, Science Direct, Health Research Premium - PROQUEST, Scopus. Cochrane Library). The search strategy yielded 21,616 studies and only three randomised controlled trials fulfilled the eligibility criteria. These trials included 125 participants (n = 50 medical students and n = 75 nursing students) and evaluated the effectiveness of a disabled health course, disability education module with bedside teaching and wheelchair workshop intervention. Findings from one study revealed that a disabled health course using affective learning method based on a transformative learning theory significantly improves attitudes to disability amongst nursing students however there was no statistically significant difference in empathy levels. More high-quality randomised controlled trials with greater theoretical and methodological complexity are needed to identify more effective educational approaches that enhance attitude and empathy levels of these key stakeholders.

Background The phenomenon of an ageing population is being experienced globally requiring the ongoing provision of residential care services. A large number of registered nurses work in these settings; however, many challenges exist in their recruitment and retention. Objectives To explore professional identities and emerging discourses of registered nurses working in older person residential care settings. Methods This study employed a discursive-based research methodology with a central focus on the role language, and discourses play in identity construction. Fourteen in-depth narrative interviews were completed with registered nurses in residential care settings in the Republic of Ireland. Thematic analysis was underpinned by a critical discursive psychology framework. Results Four key identities and related discourses emerged: 'skilled professional identity', 'person-centred identity', 'subordinate identity' and 'product of healthcare reform identity'. Discourses presented contrasting professional identities held by nurses in residential care settings; on the one hand, they employed positive professional and person-centred discourses, while on the other hand, tensions associated with healthcare reform and a subordinate identity exist. Conclusions This study presents unique insights into how registered nurses in residential care construct their professional identity and in doing so, enhances opportunities to promote recruitment and marketing in this setting. Equally, the challenges and opportunities of healthcare reform require sensitive management so that the professional identity of nurses working in residential care is enhanced and protected. Implications for practice How registered nurses working in residential care settings view their professional identity directly impacts on attitudes and behaviours and the subsequent delivery of care. Greater understanding and insight into how they construct their professional identity may enhance recruitment and retention initiatives. Study results also provide an opportunity for policymakers and service providers to create more positive working environments that promote professional identity development for this nursing group.

Abstract Background Regular ingestion of sub-hallucinogenic doses of psychedelics, referred to as “microdosing”, has gained increasing popularity and attention in the press and in online forums, with reported benefits across multiple cognitive and emotional domains. Rigorously controlled studies to date, however, have been limited in scope and have failed to produce results comparable to those reported in the grey literature. Methods Eighty healthy male participants will receive 14 doses of placebo or 10 μg lysergic acid diethylamide orally every 3rd day over a 6-week treatment protocol. A battery of personality, creativity, mood, cognition, and EEG plasticity measures, as well as resting-state fMRI imaging, will be administered at baseline and at the end of the protocol. Creativity, mood, and plasticity measures will additionally be assessed in the acute phase of the first dose. Daily functioning will be monitored with questionnaires and a wearable sleep and activity tracker. Discussion This study will rigorously examine the claims presented in the microdosing grey literature by pairing a comparable dosing protocol with objective measures. Potential therapeutic implications include future clinical trials to investigate microdosed psychedelics as a standalone treatment or as an augmentation of psychotherapy in the treatment of depression, addiction, eating disorders, obsessive-compulsive disorders, and palliative care. Trial registration ACTRN12621000436875 . Registered on 19 February 2021

BACKGROUND:Healthcare professionals working in acute settings lack education and training in dementia care, resulting in people living with dementia receiving a reduced quality of care. Discourses are ways of communicating through written and spoken language, and healthcare professionals often adopt ageist discourses when constructing the identities of people living with dementia.AIM:To explore how healthcare professionals working in acute settings construct the identities of people living with dementia.METHOD:Semi-structured interviews were conducted with nine participants working in acute settings in the Republic of Ireland.FINDINGS:Participants adopted two main discourse areas to construct the identities of people with dementia. The first discourse area related to the act of caring and the second discourse area, described as 'identity discourses', centred on the everyday language used by healthcare professionals. While participants strived to be person-centred the culture of acute settings was often task orientated.CONCLUSION:Caring for people with dementia is challenging in the acute healthcare setting. There is a need for ongoing training and effective continuing professional development strategies.

Background: In Ireland, recruiting nurses to work in residential care settings for older people is a challenge. Evidence suggests that nurses employed in this space feel devalued and lack status when compared to their colleagues employed in the acute sector. Furthermore, nurse graduates describe it as a less attractive career choice. Such negative constructions can directly impact on the recruitment and retention of such vital members of the healthcare team. How nurses construct their identities influence their behaviours, how they engage with policy and ultimately it effects the care patients receive. This study examined the professional identity of nurses employed in residential settings for older people. Methods: With a focus on language, this study employed a discourse based methodology. Identity is viewed as ever changing, constructed and reconstructed through interaction. Data is currently being collected through semi-structured interviews that utilises a narrative approach with nurses and other healthcare professionals. The influence discourses have on the construction and reconstruction of identities of nurses employed in residential care settings for older persons has yet to be explored from a national or international perspective. Results: Preliminary findings suggest that multiple identities and discourses exist and are influenced by wider social and historical norms. Through exploration and discovery, it is hoped this study will enhance the professional identity of nurses working in this field and recognise the invaluable contribution they make to older person care in Ireland. Conclusions: The study of nursing identity is significant as it offers insight into how the profession perceives itself and is perceived by others. Nursing identities develop in the working environment, thus influencing certain behaviours in inter-professional working, and clinical decision-making. The outcomes of this study have the potential to influence policy and marketing developments in this specific area of nursing practice and ultimately improve patient care.

Acute healthcare professionals lack education and training in dementia care. This results in people with dementia having poorer outcomes when admitted to the acute healthcare setting. An overarching aim of The National Dementia Strategy (2014) is the provision of optimal care for people with dementia in all healthcare and community settings. In response to this, Dementia Elevator a national inter-professional suite of educational programmes were developed by Dublin City University and the Health Service Executive to help individuals, communities and health systems engage positively with people with dementia. This study aimed to evaluate the impact of a four-hour dementia training programme on acute healthcare professionals’ attitudes and understanding of dementia. A mixed methods research methodology was employed to answer the research questions. Questionnaires and semi structured interviews were the chosen research methods utilised. The first phase of this study employed a quantitative approach (n=42), and the second phase employed a qualitative approach (n=9). The findings from this study indicate that participants’ attitudes to dementia were high and were enhanced as a result of the training programme. There was a statistical significant difference in attitudes post the educational intervention illustrating healthcare professionals’ optimism towards the abilities and future of individuals with dementia. Participants adopted a range of discourse when constructing people with dementia including: competency to care, emotional challenges and organisational culture. Furthermore, wider discourses were drawn upon by participants that constructed identities of people with dementia. Overall, healthcare professionals strived to deliver person-centered care but were impeded owing to the task focused culture within the acute setting and emotional challenges. Acute care settings must become more dementia-friendly for individuals with dementia owing to the findings of this study with a focus on environment, staff competency and the overall organisational culture of these settings. Healthcare professionals require further education and training in the area of dementia and the promotion of a person-centered approach to care.

Potential difficulties experienced by nursing students diagnosed with dyslexia can be minimised with the introduction of appropriate policies and guidance around reasonable adjustment and support. In order to access all relevant services, however, a student must actively decide to disclose their dyslexic identity to relevant faculty personnel. Disclosure of such personal information is a complex matter and, critically, requires a receptive environment where diversity and disability are embraced in a positive and meaningful way. The act of disclosure for the most part has previously been described in simplistic terms, with the focus being solely on the behaviour itself and not on the individual's own positioning of their dyslexia or the social context associated with the act. There is an onus on all students with dyslexia to self-monitor how this aspect of their identity interacts with their professional duty of care.