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Abstract Introduction : There are limited therapeutic options for individuals with fibromyalgia. The aim of this study is to analyze changes in health‐related quality of life and incidence of adverse events of those prescribed cannabis‐based medicinal products (CBMPs) for fibromyalgia. Methods : Patients treated with CBMPs for a minimum of 1 month were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in validated patient‐reported outcome measures (PROMs). A p‐value of

Introduction: Cannabis-based medicinal products (CBMPs) have been identified as a promising novel therapeutic for symptoms and comorbidities related to autism spectrum disorder (ASD). However, there is a paucity of clinical evidence of their efficacy and safety. Objective: This case series aims to assess changes to health-related quality of life and the incidence of adverse events in patients treated with CBMPs for associated symptoms of ASD enrolled on the UK Medical Cannabis Registry (UKMCR). Methods: Patients treated with CBMPs for ASD-related symptoms for a minimum of 1 month were identified from the UKMCR. Primary outcomes were changes in validated patient-reported outcome measures [Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), 5-level version of the EQ-5D (EQ-5D-5L) index values] at 1, 3 and 6 months compared with baseline. Adverse events were recorded and analysed. Statistical significance was determined by p

The mystical experience is a potential psychological mechanism to influence outcome in psychedelic therapy. It includes features such as oceanic boundlessness, ego dissolution, and universal interconnectedness, which have been closely linked to both symptom reduction and improved quality of life. In this review, 12 studies of psychedelic therapy utilizing psilocybin, ayahuasca, or ketamine were analyzed for association between mystical experience and symptom reduction, in areas as diverse as cancer-related distress, substance use disorder, and depressive disorders to include treatment-resistant. Ten of the twelve established a significant association of correlation, mediation, and/or prediction. A majority of the studies are limited, however, by their small sample size and lack of diversity (gender, ethnic, racial, educational, and socioeconomic), common in this newly re-emerging field. Further, 6 out of 12 studies were open-label in design and therefore susceptible to bias. Future studies of this nature should consider a larger sample size with greater diversity and thus representation by use of randomized design. More in-depth exploration into the nature of mystical experience is needed, including predictors of intensity, in order to maximize its positive effects on treatment outcome benefits and minimize concomitant anxiety.Systematic Review Registration: PROSPERO, identifier CRD42021261752.

Global warming is amplified in the Arctic. However, numerical models struggle to represent key processes that determine Arctic weather and climate. To collect data that help to constrain the models, the HALO–(𝒜𝒞)3 aircraft campaign was conducted over the Norwegian and Greenland seas, the Fram Strait, and the central Arctic Ocean in March and April 2022. The campaign focused on one specific challenge posed by the models, namely the reasonable representation of transformations of air masses during their meridional transport into and out of the Arctic via northward moist- and warm-air intrusions (WAIs) and southward marine cold-air outbreaks (CAOs). Observations were made over areas of open ocean, the marginal sea ice zone, and the central Arctic sea ice. Two low-flying and one long-range, high-altitude research aircraft were flown in colocated formation whenever possible. To follow the air mass transformations, a quasi-Lagrangian flight strategy using trajectory calculations was realized, enabling us to sample the same moving-air parcels twice along their trajectories. Seven distinct WAI and 12 CAO cases were probed. From the quasi-Lagrangian measurements, we have quantified the diabatic heating/cooling and moistening/drying of the transported air masses. During CAOs, maximum values of 3 K h−1 warming and 0.3 g kg−1 h−1 moistening were obtained below 1 km altitude. From the observations of WAIs, diabatic cooling rates of up to 0.4 K h−1 and a moisture loss of up to 0.1 g kg−1 h−1 from the ground to about 5.5 km altitude were derived. Furthermore, the development of cloud macrophysical (cloud-top height and horizontal cloud cover) and microphysical (liquid water path, precipitation, and ice index) properties along the southward pathways of the air masses were documented during CAOs, and the moisture budget during a specific WAI event was estimated. In addition, we discuss the statistical frequency of occurrence of the different thermodynamic phases of Arctic low-level clouds, the interaction of Arctic cirrus clouds with sea ice and water vapor, and the characteristics of microphysical and chemical properties of Arctic aerosol particles. Finally, we provide a proof of concept to measure mesoscale divergence and subsidence in the Arctic using data from dropsondes released during the flights.

Abstract Background Research on cannabis‐based medicinal products (CBMPs) in anxiety remains inconclusive due to a paucity of high‐quality evidence. Studies indicate a bidirectional relationship between generalized anxiety disorder (GAD) and sleep disruption, but it is unclear how this affects CBMP treatment outcomes. This study aims to compare the patient‐reported outcome measures (PROMs) of patients prescribed CBMPs for GAD, with and without impaired sleep. Methods Changes in PROMs were recorded from baseline to 1, 3, 6, and 12 months between those with impaired or unimpaired sleep. Multivariate logistic regression was applied to compare factors associated with a clinically significant improvement in GAD‐7 at 12 months. Secondary outcomes included adverse event incidence and frequency. Results Of the 302 patients that fit the inclusion criteria, mean GAD‐7, single‐item sleep quality, and EQ‐5D‐5L index values improved at all time points (p

Psilocybin is a classic psychedelic drug that has attracted increasing research interest over the past 10 years as a possible treatment for mood, anxiety and related conditions. Initial phase 2 clinical trials of psilocybin given alongside psychological support for major depression and treatment-resistant depression (TRD) demonstrated encouraging signs of basic safety, further confirmed by a large study in groups of healthy volunteers. The first international multi-centre randomised controlled trial was published in 2022, with signs of efficacy for the 25 mg dose condition in people with TRD when compared with an active placebo. Phase 3 trials in TRD are scheduled to start in 2023. Early evidence suggests that single doses of psilocybin given with psychological support induce rapid improvement in depressive symptoms that endure for some weeks. We therefore provide a timely update to psychiatrists on what psilocybin therapy is, what it is not, and the current state of the evidence-base.

Abstract Aim This study aims to analyze the health‐related quality of life (HRQoL) and safety outcomes in attention‐deficit/hyperactivity disorder (ADHD) patients treated with cannabis‐based medicinal products (CBMPs). Methods Patients were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the following patient‐reported outcome measures (PROMs) at 1, 3, 6, and 12 months from baseline: EQ‐5D‐5L index value, generalized anxiety disorder‐7 (GAD‐7) questionnaire, and the single‐item sleep quality score (SQS). Secondary outcomes assessed the incidence of adverse events. Statistical significance was defined as p

Abstract Introduction While there is increasing evidence of the effects of cannabis‐based medicinal products (CBMPs) on health‐related quality of life (HRQoL), a major limitation of the current literature is the heterogeneity of studied CBMPs. This study aims to analyze changes in HRQoL in patients prescribed a homogenous selection of CBMPs. Methods Primary outcomes were changes in patient‐reported outcomes (PROMs) at 1, 3, 6, and 12 months from baseline. The secondary outcome was an adverse events analysis. Statistical significance was defined as p 0.050). 3663 (265.82%) adverse events were reported by 297 (21.55%) patients. Conclusion There was an associated improvement in self‐reported anxiety, sleep quality, and HRQoL in patients treated with the CBMPs. Those prescribed treatment formulations including dried flower were most likely to show a clinical improvement. However, these results must be interpreted with caution given the limitations of study design.

Abstract Introduction The primary aim of this study was to assess changes in sleep‐specific health‐related quality of life (HRQoL) for those prescribed cannabis‐based medicinal products (CBMPs) for insomnia. Methods A case series of UK patients with insomnia was analyzed. Primary outcomes were changes in the Single‐Item Sleep‐Quality Scale (SQS), Generalized Anxiety Disorder‐7 (GAD‐7), and EQ‐5D‐5L at up to 6 months from baseline. Statistical significance was identified as a p value < .050. Results 61 patients were included in the analysis. There was an improvement in the SQS from baseline at 1, 3, and 6 months (p < .001). There were also improvements in the EQ‐5D‐5L Index value and GAD‐7 at 1, 3, and 6 months (p < .050). There were 28 (45.9%) adverse events recorded by 8 patients (13.1%). There were no life‐threatening/disabling adverse events. Conclusion Patients with insomnia experienced an improvement in sleep quality following the initiation of CBMPs in this medium‐term analysis. Fewer than 15% of participants reported one or more adverse events. However, due to the limitations of the study design, further investigation is required before definitive conclusions can be drawn on the efficacy of CBMPs in treating insomnia.

Background and Aims: This is the first systematic review of the extant literature on all major psychedelic-assisted treatment for alcohol use disorder (AUD), tobacco use disorder (TUD) and other substance use disorders (SUD). We aimed to summarise the evidence for efficacy of psychedelic-assisted treatment for AUD, TUD, and SUD; to evaluate its quality; and to offer recommendations for research., Methods: This was a prospectively registered narrative systematic review of open-label, randomised controlled trials (RCT), and observational studies of d-lysergic acid diethylamide (LSD), mescaline, psilocybin, ayahuasca, ketamine, ibogaine and 3,4-methylenedioxymethamphetamine (MDMA). Eligible studies had SUD outcome measures including craving, substance use, relapse, and remission. Study quality was evaluated using the Cochrane Collaboration Risk of Bias (RoB), and Cochrane Collaboration RoB in Non-randomised Studies of Interventions tool. Certainty of evidence for RCTs was judged using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool., Findings: 37 studies (2035 participants) were reviewed: LSD (14; n = 1047); mescaline (1; n = 7); psilocybin (4; n = 135); ayahuasca (3; n = 101); ketamine (10; n = 579); ibogaine (5; n = 166); and MDMA (1; n = 14). There were no serious adverse events reported in any study. A two-centre, placebo-controlled, phase 2 superiority RCT of psilocybin for AUD, and a two-centre, double-blind, four-arm, placebo-controlled phase 2 RCT of ketamine for AUD yielded the best evidence of efficacy. Progression support to a phase 3 trials was secured from an open-label phase 2 study of psilocybin for TUD and nine phase 2 RCTs of ketamine for AUD, cannabis use disorder, cocaine use disorder, and opioid use disorder (all nine with high-RoB and low-GRADE evidence certainty)., Conclusions: Psilocybin-assisted treatment for alcohol use disorder appears to have the best evidence of efficacy among all major psychedelic-assisted treatments for alcohol, tobacco, and other substance use disorders. Future research of psychedelic-assisted treatment should report all safety events; screen for person-level characteristics indicating that psychedelic-assisted substance use disorders treatment is contraindicated; strive to mitigate blinding of participants to interventions; use factorial designs for drug and psychotherapy randomised controlled trials; and build consensus for a field-specific Core Outcome Set., (© 2025 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Psychedelic drugs are a focus of interest in the treatment of depression and other disorders but there are longstanding concerns about possible adverse psychiatric consequences. Because the relevant literature is largely informal, the seriousness of these risks is difficult to evaluate., Methods: Searches were made for case reports of schizophrenia-spectrum, affective or other psychiatric disorders after use of psychedelic drugs. Case reports of flashbacks were also searched for. Individuals with recent use of other drugs (apart from cannabis and alcohol) and/or a previous history of major psychiatric disorder were excluded. Symptoms were tabulated using the Syndrome Check List of the Present State Examination (PSE-9)., Results: We found 17 case reports of schizophrenia spectrum disorder, 17 of affective disorder (depression, mania, or both), 3 cases of anxiety, 1 of depersonalization, and 1 of unclassifiable illness. The states could develop after a single use of the drug (5/17 schizophrenia; 6/17 affective disorder), and duration was highly variable. Recovery was the rule in cases of affective disorder but not in schizophrenia spectrum disorder. Twelve of 29 cases of flashbacks showed psychiatric symptomatology definitely outlasting the attacks, mainly anxiety (5 cases) and depression (8 cases). Flashback symptoms resolved within twelve months in approximately half of the cases but in a few persisted for years., Conclusions: Reliable descriptions of schizophrenia spectrum disorder and major affective disorder after psychedelic drug use disorder exist but are relatively uncommon. Flashbacks are sometimes but not always associated with psychiatric symptomatology, mainly anxiety or depression.

Background: Short-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgias that feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency., Methods: Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes., Results: No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re-configured relationships to their headache pain., Conclusion: The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Psychedelic drugs have seen a resurgence in interest as a next generation of psychiatric medicines with potential as rapid-acting antidepressants (RAADs). Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent mechanisms are unresolved. Preclinical studies in relevant animal models are key to understanding the pharmacology of psychedelics and translating these findings to explain efficacy and safety in patients. Understanding the mechanisms of action associated with the behavioural effects of psychedelic drugs can also support the identification of novel drug targets and more effective treatments. Here we review the behavioural approaches currently used to quantify the psychedelic and antidepressant effects of psychedelic drugs. We discuss conceptual and methodological issues, the importance of using clinically relevant doses and the need to consider possible sex differences in preclinical psychedelic studies., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted in seven individuals with early-stage ALS. Participants were given 3 months of home-based resistance exercise focusing on the quadriceps muscles. The strength of exercised muscle was evaluated using bilateral quadriceps strength with manual muscle testing, handheld dynamometers, five times sit-to-stand, and Timed-Up-and-Go before and after the exercise program. In addition, changes in the Sickness Impact Profile ALS-19 (SIP/ALS-19) as the functional outcome measure and the transcriptome of exercised muscles were compared before and after the exercise. The primary outcome of muscle strength did not change significantly by the exercise program. The exercise program maintained the SIP/ALS-19 and the ALS Functional Rating Scale-Revised (ALSFRS-R). Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including parvalbumin. Three months of moderately intense strength and conditioning exercise maintained muscle strength of the exercised muscle and ALSFRS-R scores and had a positive effect on patients' muscle transcriptome., (© 2024. The Author(s).)

Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder., Protocol: In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet's clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place., Discussion: The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population., Competing Interests: Competing interests: M.J.E. does medical expert reporting in personal injury and clinical negligence cases, including in cases of functional neurological disorder (FND). M.J.E. has shares in Brain & Mind, which provides neuropsychiatric and neurological rehabilitation in the independent medical sector, including in people with functional neurological disorder. M.J.E. has received financial support for lectures from the International Parkinson's and Movement Disorders Society and the FND Society (FNDS). M.J.E. receives royalties from Oxford University Press for his book The Oxford Specialist Handbook of Parkinson's Disease and Other Movement Disorder. M.J.E has received honoraria for medical advice to Teva Pharmaceuticals. M.J.E. receives grant funding, including for studies related to FND, from the National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC). M.J.E. is an associate editor of the European Journal of Neurology. M.J.E. is a member of the international executive committee of the International Parkinson's and Movement Disorders Society and a board member of the FNDS. M.J.E. is on the medical advisory boards of the charities FND Hope UK and Dystonia UK. The study medication is provided by COMPASS Pathways Ltd who will receive adverse events information from the study practitioners., (Copyright: © 2024 Butler M et al.)

Background: There has been a resurgence of research into the potential therapeutic benefits of psychedelics for neuropsychiatric disorders. Classic psychedelics, such as psilocybin, exert complex effects on higher cognitive functions such as perception and awareness, but their impact on motor function remains unexplored. Moreover, there is a theoretical rationale for using psychedelics to promote motor retraining in certain neuropsychiatric conditions associated with motor dysfunction. This protocol paper outlines the first study to investigate the feasibility and safety of performing movement tasks during the acute effects of psilocybin in healthy participants. The findings from this study will further our understanding of the impact of psychedelics on motor function, and inform future studies that combine classic psychedelics with motor retraining in clinical populations., Methods: 12 healthy participants will each receive three doses of psilocybin (between 5 and 20 mg) in a randomized order, with each dose administered at least 1 week apart. Participants, the trial physiotherapists, and statisticians will remain blinded to the psilocybin dose. A battery of measures assessing motor function will be completed during the acute drug effects. In addition, measures of safety, pre- and post-dose resting-state brain activity via functional magnetic resonance imaging, and participants' subjective experience will be assessed., (© 2024 The Author(s). Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)

Pre-prohibition psychedelic research with complex psychiatric patients generated a wealth of treatment methodologies and practices, providing invaluable clinical insights pertaining to the medical administration of psychedelics in various mental health diagnoses. Building upon these early studies, which lack the rigor and research tools available today, contemporary psychedelic research has focused on investigating the safety and efficacy of psychedelics in randomized controlled trials via psychometric measures and symptom assessments. Both then and now, the treatment context and the role of clinicians in psychedelic treatment has been recognized as an essential feature for positive patient outcomes. To broaden the knowledge base of modern psychedelic research and support the training of clinicians conducting medically supervised psychedelic research studies, this paper provides a review of pre-prohibition clinical research narratives pertaining to the phenomenology of psychedelic treatment and the role of the non-pharmacological treatment factors in the patient experience. Lastly, this paper explores a range of clinician perspectives and psychological interventions employed in pre-prohibition psychedelic research to inform future research directions and best practice guidelines., (© 2024. The Author(s).)

The aim of this study was to assess changes in validated patient-reported outcome measures after initiation of cannabis-based medicinal products (CBMPs) and the safety of CBMPs in patients with inflammatory arthritis. A prospective case series from the UK Medical Cannabis Registry was analyzed. The primary outcomes changes were in Brief Pain Inventory, McGill Pain Questionnaire, EuroQol 5-dimension 5-level (EQ-5D-5L), Generalised Anxiety Disorder-7 questionnaire, and Single-Item Sleep Quality Scale at 1, 3, 6, and 12 months of follow-up compared with baseline. Adverse events were analyzed in accordance with Common Terminology Criteria for Adverse Events, v.4.0. Statistical significance was defined as a P-value less than 0.050. Eighty-two patients met the inclusion criteria. Initiation of CBMP treatment was associated with improvements in Brief Pain Inventory, McGill Pain Questionnaire, EQ-5D-5L, Generalised Anxiety Disorder-7 questionnaire, and Single-Item Sleep Quality Scale at 1, 3, 6, and 12 months compared with baseline (P < 0.050). There were 102 (44.35%) mild adverse events, 97 (42.17%) moderate adverse events, and 31 (13.48%) severe adverse events recorded by 21 (25.61%) participants. This study suggests that CBMP treatment is associated with pain improvement and increased health-related quality of life for inflammatory arthritis patients. While causality cannot be inferred in this observational study, the results support the development of randomized control trials for inflammatory arthritis pain management with CBMPs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Osteoarthritis accounts for 0.6% of disability-adjusted life years globally. There is a paucity of research focused on cannabis-based medicinal products (CBMPs) for osteoarthritic chronic pain management. This study aims to assess changes in validated patient-reported outcome measures (PROMs) and CBMP clinical safety in patients with osteoarthritis. A prospective case series from the UK Medical Cannabis Registry was analyzed. Primary outcomes were changes in the Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ2), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) questionnaire, and Single-Item Sleep Quality Scale (SQS) at 1-, 3-, 6-, and 12-month follow-ups from baseline. Common Terminology Criteria for Adverse Events v.4.0 was used for adverse event (AE) analysis. Statistical significance was defined as p  < 0.050. Seventy-seven patients met inclusion criteria. CBMP initiation correlated with BPI pain severity ( p  = 0.004), pain interference ( p  = 0.005), and MPQ2 ( p  = 0.017) improvements at all follow-ups compared to baseline. There were improvements in the EQ-5D-5L index ( p  = 0.026), SQS ( p  < 0.001), and GAD-7 ( p  = 0.038) up to 6 and 3 months, respectively. Seventeen participants (22.08%) recorded 76 mild AEs (34.86%), 104 moderate AEs (47.71%), and 38 severe AEs (17.43%). Though causality cannot be assumed in this observational study, results support development of randomized control trials for osteoarthritis pain management with CBMPs.

Aims: Concerted, effective, and sustainable change in healthcare education programs is a critical step towards creating more diverse, inclusive, and equitable professions. This commentary demonstrates how one entry-level physical therapist education program, through a process of reflection, prioritization, and action, is taking steps to increase diversity, equity, and inclusivity within their program., Rationale: This article highlights initiatives that are leveraging existing partnerships and creating new ones to reach and mentor students from diverse communities, steps taken towards a more holistic and equitable admissions process, implementation of curricular changes to intentionally discuss the social determinants of health, and engagement of faculty and students to foster personal and professional development on diversity, equity, and inclusion topics. Outcomes to track the effectiveness of the strategies being used by each initiative are shared., Conclusion: To create active agents of change, education programs must create a diverse and equitable space for students and guide them to become leaders who can transform society. Steps taken by an entry-level physical therapist education program to implement strategies to promote diversity, equity and inclusion can serve as a road map for other healthcare professional programs.

The conceptualization of personality disorder has been refined through recent nosological advances introduced in the Alternative Model for Personality Disorders (AMPD). These advances locate self and interpersonal (dys)function at the core of personality pathology. Self-report personality assessment instruments have demonstrated promise in the assessment of Criterion A domains. However, research highlighting the utility of performance-based personality assessment instruments has been largely absent in these advances, despite acknowledgment of their potential. We adhered to PRISMA review guidelines to survey and assess the potential relevance and utility of select performance-based personality instruments in assessing Criterion A domains of the AMPD. We conclude that performance-based personality measures are uniquely positioned to assess maladaptive self- and interpersonal functioning and may address some limitations of self-report measures. Toward this end, we propose a working model that provides ranges of test scores that correspond to the 5-point scale of the Criterion A domains of the AMPD.

Objective: To capture UK medical students' self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research., Design: Cross-sectional, anonymous online survey of UK medical students using a non-random sampling method., Setting: UK medical schools recognised by the General Medical Council., Participants: 132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1-6) in medical school., Results: Most students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students' harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p<0.001), lower estimated harm scores (p<0.001), more time spent in medical school (p=0.024) and lower perceived effectiveness of non-pharmacological mental health treatments (p=0.044) were associated with greater support for legal status change., Conclusions: Our findings reveal a significant interest among UK medical students to learn more about psychedelic research and a strong support for further psychedelic research. Future studies are needed to examine how medical education could be refined to adequately prepare medical students for a changing healthcare landscape in which psychedelic-assisted therapy could soon be implemented in clinical practice., Competing Interests: Competing interests: JR has received payments for advisory work from Clerkenwell Health (Past), Beckley PsyTech (Past), Delica Therapeutics (Past), for articles written for Janssen, and financial assistance for attendance at conferences from Compass Pathways (past) and Janssen. JR has received grant funding (received and managed by King’s College London) from Compass Pathfinder, Beckley PsyTech, Multidisciplinary Association for Psychedelic Studies, National Institute for Health Research, Wellcome Trust, Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust. All other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.

Objective: Functional neurological disorder (FND) causes a high burden of disability and distress. Although it is a common disorder, there is a pressing need for improved access to evidence-based treatments. With difficulties in finding effective treatment, some people with FND may seek alternative means of symptom relief, such as legal and illicit psychoactive substances, although the prevalence and nature of such self-management strategies are currently unclear. Additionally, psychoactive substances may represent novel treatment research opportunities, particularly for those with suboptimal improvement. The investigators examined the use of self-management techniques, as well as perspectives on novel therapies, in this patient population. Methods: An online survey was created to assess self-management strategies and views on novel treatments for FND, including psychedelic therapy. The survey was accessible for 1 month, and respondents were recruited internationally through social media and patient groups. A total of 1,048 respondents from 16 countries completed the survey. Results: Almost half (46%) of 980 respondents reported having tried legal psychoactive substances for the management of their FND symptoms and, on average, nicotine, alcohol, and cannabidiol were reported as modestly effective. Additionally, 15% of respondents reported having used illicit substances, mostly cannabis, to manage FND, with the majority reporting moderate effectiveness and experiencing no or minimal physical (90%) and psychological (95%) sequelae. Many respondents (46%) reported that they would be willing to try medically supervised psychedelic therapy (with 19% of respondents ambivalent) if it were found to be safe and effective. Conclusions: Many people with FND seek alternative means of symptom management outside usual medical care, including legal and illicit psychoactive substances. Further research exploring novel treatment options, such as psychedelics, in FND may be warranted.

Introduction: Ever since the United States Food and Drug Administration (FDA) approved aducanumab and Centers for Medicare & Medicaid Service (CMS) restricted coverage for the drug, a crucial question has been how other payers will behave. This study examined how Medicaid and commercial plans cover aducanumab., Methods: We created a database of aducanumab coverage policies issued by Medicaid fee-for-service programs (50 states and DC) and 35 of the largest commercial plans (covering ∼ 84% of the commercially insured population)., Results: We found that only 41% of Medicaid fee-for-service plans have issued a publicly available coverage policy for aducanumab and that there is wide variation in these coverage criteria. Although the majority of included commercial plans have issued an aducanumab coverage policy, only five plans covered aducanumab for their enrollees. Available coverage polices showed little consistency in how to measure sufficient treatment response., Discussion: Differences in coverage policies mean that Alzheimer's patients' access to aducanumab may vary across jurisdictions and across commercial insurers., Highlights: Less than half of state Medicaid fee-for-service plans issued a publicly available coverage policy for aducanumab. Available Medicaid coverage policies varied substantially in their coverage criteria. The majority of included commercial plans issued an aducanumab coverage policy; only five plans covered aducanumab. Available coverage polices showed little consistency in how to measure sufficient treatment response., (© 2023 Alzheimer's Association.)

Objectives: The purposes of this study were to describe the current use of (1) simulation in student physical therapist professional education programs and (2) standards of best practice (SOBP) for simulation-based education (SBE) in physical therapist education., Methods: Two surveys were created about current use of SBE in student physical therapist professional education programs in the United States. The first survey contained questions about the program, including the best contact person regarding simulation. The second survey investigated simulation use within the context of SOBP. Survey data were analyzed using descriptive statistics., Results: Survey 1 was sent to the program director at all fully accredited physical therapist programs (N = 236), and 143 responses were returned (61% response rate). Survey 2 was sent to the 136 individuals identified in Survey 1, and we received 81 completed surveys (60%). Over 90% of programs reported including SBE in their curricula, with 86% providing 3 or more experiences. A median of 1 core faculty at each program reported training in SBE, but 23% reported no training. A lack of training in specific elements of the SOBP for SBE was reported by 40% to 50% of faculty. Limited use of SOBP was reported, and use of outcome measures without validation was common., Conclusion: Although SBE is commonly used in physical therapist education, many faculties (1) do not have training in SBE, (2) do not consistently follow the SOBP, and (3) utilize unvalidated outcome measures. Limited faculty training in SBE and inconsistent inclusion of the SOBP suggest student learning in simulation is not optimized., Impact: These results show that, despite increased use of simulation in physical therapist education programs, there is a dearth of faculty trained in SBE and inconsistent use of SOBP. Addressing these deficiencies could help to optimize the benefits of SBE in physical therapist education., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the summer of 2018, The American Council of Academic Physical Therapy appointed 9 individuals versed in simulation education to form the Strategic Initiative Panel on Simulation to (1) investigate the use of simulation in physical therapist education, (2) explore the role of simulation in meeting accreditation standards and curriculum elements related to clinical education and interprofessional education, and (3) describe models and best practices for the use of simulation in physical therapist education. Over the 3 years of Strategic Initiative Panel on Simulation work, the panel identified several significant gaps in simulation education and research practice. This paper clarifies the essential elements required to optimize the delivery of simulation-based education in physical therapy following best practices, frames the existing challenges to move the profession forward, and recommends specific actions needed to address the many continued questions related to the effective use of simulation-based education in physical therapist education., (© 2022 American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purposes of this study were to (1) describe and summarize the use of simulation-based education (SBE) with student physical therapists in the international literature and (2) describe the application and integration of standards of best practice (SOBP) for SBE reported in published physical therapy education research., Methods: Ovid MEDLINE, CINAHL, Web of Science, and ERIC databases were searched. The search included any published study that involved the use of SBE with student physical therapists. Because this was a scoping review, only descriptive statistics were compiled; no methodological quality assessment was performed., Results: This scoping review revealed a significant increase in literature describing SBE with student physical therapists in the past 10 years. Simulation was used to address learning objectives across a variety of content areas and clinical settings. Communication skills were the most common objectives for simulation. Limited use of SOBP, published in 2016, was reported, and use of author-generated outcome measures without validation was common., Conclusions: Although there has been an increase in literature reporting the use of SBE with student physical therapists across many practice areas and settings, many articles reported limited use and integration of published SOBP and frequently utilized outcome measures that had not been validated., Impact: The findings show that limited use of validated outcome measures and SOBP constrain the capacity for reproducing studies, comparing findings among studies, and completing systematic reviews that could inform and optimize best practices for the use of SBE in physical therapist professional education. Further research on SBE in physical therapy would benefit from investigations that integrated and reported the use of SOBP for standardized patients, simulation design, and delivery and assessment of learning outcomes over time at multiple Kirkpatrick learning levels., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Psilocybin is being studied for use in treatment-resistant depression., Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits)., Results: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups., Conclusions: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.)., (Copyright © 2022 Massachusetts Medical Society.)

Modern psychedelic research remains in an early phase, and the eventual introduction of psychedelics into clinical practice remains in doubt. In this piece, we discuss the role of blinding and expectancy in psychedelic trials, and place this in a broader historical and contemporary context of blinding in trials across the rest of healthcare. We suggest that premature and uncritical promotion ('hype') of psychedelics as medicines is not only misleading, but also directly influences participant expectancy in ongoing psychedelic trials. We argue that although psychedelic trials are likely to significantly overestimate treatment effects by design due to unblinding and expectancy effects, this is not a unique situation. Placebo-controlled RCTs are not a perfect fit for all therapeutics, and problems in blinding should not automatically disqualify medications from licencing decisions. We suggest that simple practical measures may be (and indeed already are) taken in psychedelic trials to partially mitigate the effects of expectancy and unblinding, such as independent raters and active placebos. We briefly suggest other alternative trial methodologies which could be used to bolster RCT results, such as naturalistic studies. We conclude that the results of contemporary placebo-controlled RCTs of psychedelics should neither be dismissed due to imperfections in design, nor should early data be taken as firm evidence of effectiveness., (© 2022. The Author(s).)

Background: 5-Methoxy- N,N -dimethyltryptamine (5-MeO-DMT) is a naturally occurring, short-acting psychedelic tryptamine, produced by a variety of plant and animal species. Plants containing 5-MeO-DMT have been used throughout history for ritual and spiritual purposes. The aim of this article is to review the available literature about 5-MeO-DMT and inform subsequent clinical development., Methods: We searched PubMed database for articles about 5-MeO-DMT. Search results were cross-checked against earlier reviews and reference lists were hand searched. Findings were synthesised using a narrative synthesis approach. This review covers the pharmacology, chemistry and metabolism of 5-MeO-DMT, as well epidemiological studies, and reported adverse and beneficial effects., Results: 5-MeO-DMT is serotonergic agonist, with highest affinity for 5-HT 1A receptors. It was studied in a variety of animal models, but clinical studies with humans are lacking. Epidemiological studies indicate that, like other psychedelics, 5-MeO-DMT induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being., Conclusion: 5-MeO-DMT is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences. We conclude that further clinical exploration is warranted, using similar precautions as with other classic psychedelics.