How to set up a psychedelic study: Unique considerations for research involving human participants.

The rapid growth in psychedelic research raises novel ethical challenges for both research and psychedelic-assisted therapy. Despite these challenges, there is no consensus among researchers, clinicians, patients, and regulators on how these ethical issues may be avoided or managed. This study aimed to identify key ethical issues in psychedelic research and practice in the literature. A scoping review was performed, identifying fifty-one relevant articles. Content analysis revealed five main ethical concerns in the literature: 1) standards of practice, 2) equity, 3) integrity, 4) cultural appropriation, and 5) epistemic justice. A consultation workshop highlighted several key concerns that were neglected in the literature: 1) post-trial care, 2) lack of consensus on models of care and psychedelic practitioner competencies, and 3) how current research and its associated ethical issues will be translated into practice. Based on these findings the following future directions are recommended: designing clear competency frameworks, increased consultation with Indigenous and priority populations (e.g. ethnic and cultural minorities, under-served groups), guidelines for Indigenous recognition, management of post-trial care in clinical trials, and adequate governance of psychedelic prescribing practices.

The primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin. Despite initial concerns that psilocybin could cause psychosis, contemporary research has demonstrated that psilocybin is generally safe. The most common adverse effects are nausea and headache, yet both tend to be transient. Serious adverse events can generally be avoided in controlled settings such as clinical trials. However, in the largest clinical trial to date, there were a total of 7 reported cases of suicidal ideation, up to 12 weeks after receiving a single 25 mg dose of psilocybin. That being said, all 7 cases did not respond to the treatment. Although selective serotonin reuptake inhibitors may blunt the hallucinogenic qualities of psilocybin, preliminary research suggests that they may enhance its antidepressant effects. In clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses. However, larger Phase II trials with more than 100 depressed participants have shown a much smaller remission rate of 25%-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms. Aside from ketamine, psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and multiple therapeutic applications. Phase III trials will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.

Primary care providers have reported feeling ill-equipped to care for transgender and gender diverse (TGD) patients because of lack of training, and their treatment of acne has been shown to be variable and not standardized. This is an important practice gap, as TGD youth represent a historically underserved population in medicine, despite data suggesting that up to 9.2% of high school-age adolescents identify as TGD. Although needs and expectations for quality health-care in TGD youth do not necessarily differ from their cisgender peers, TGD adolescents have unique considerations in their care and are at risk for negative social and emotional outcomes secondary to minority stress, discrimination, and rejection by peers and family. Acne is estimated to affect approximately 85% of adolescents and is associated with negative mental health outcomes, including suicidal ideation, low self-esteem, and depression. As such, knowledgeable and culturally informed care of acne in TGD adolescents has important implications for quality of life for patients who desire effective treatment. This review article addresses these practice gaps by summarizing an approach to acne evaluation and management with an emphasis on appropriate regimens for TGD youth, and the unique psychosocial and medical considerations for this population.

Nonalcoholic Fatty Liver Disease in Children: Where Are We?

Prior data indicate limited ethnoracial diversity in studies testing psychedelic-assisted treatments. Regulatory approval for psychedelic treatments may be imminent given growing evidence for safety and efficacy in a variety of psychiatric conditions. Data on racial and ethnic inclusion rates in clinical psychedelic studies since 2018 have not been systematically reported to date. With the publication of multiple new studies in the field, an update to existing ethnoracial inclusion data is needed to inform the state of the science and future directions for research. Systematic review of Pubmed/MEDLINE, EMBASE, and Web of Science for studies of any design testing a psychedelic treatment for a psychiatric or substance use disorder published between January 1, 1994 and May 24, 2024. Search terms related to serotonergic psychedelics and MDMA, psychedelic therapies, psychiatric disorders, and substance use disorders were used. References of reviewed studies were screened for inclusion. Studies were rated for quality on a five-point scale ranging from 1 (most rigorous, i.e., properly powered randomized clinical trial) to 5 (least rigorous, e.g., case reports). Separate analyses were performed for two groups of studies, one involving all included studies meeting search criteria, and the other involving only studies from the USA. Rates of inclusion of different ethnoracial groups were calculated between studies published before and after December 31, 2017. Additionally, the proportion of White vs. non-White participants was compared between studies published before and after December 31, 2017. Finally, a nonparametric Mann-Whitney U test was used to compare the relative quality ratings of studies published before and after December 31,2017. 787 studies were screened, and 39 studies were included. This included 16 studies (n=282) from a prior review published in 2018 with an additional 23 studies (n=1111) that were published after 2017, consisting of 14 randomized controlled studies, 8 open-label studies, and 1 placebo-controlled, within-subject, fixed-order study. In all included studies published after 2017, 85.6% of participants identified as non-Hispanic White, 3.1% as Black, 6.8% as Latinx/Hispanic, 3.6% as Asian, 1.2% as Indigenous, 3.5% as mixed race, 1.4% as other, Pooled data from all included studies (n=1393) found 85.0% of participants identified as non-Hispanic White, 2.9% as Black, 5.9% as Latinx/Hispanic, 3.2% as Asian, 1.9% as Indigenous, 3.7% as mixed race, 1.4% as other. In studies conducted in the USA (n=1074), 908 (84.5%) of participants identified as White, 36 (3.4%) as Black, 80 (7.4%) as Latinx/Hispanic, 43 (4.0%) as Asian, 15 (1.4%) as Indigenous, 40 (3.7%) as Mixed, and 9 (0.8%) as Other. Differences in inclusion rates were found when comparing studies published before and after December 31, 2017 for all included studies and all studies conducted in the USA. The proportion of White to non-White participants was found to have decreased in studies conducted in the USA over the same period, but not for all included studies. Underrepresentation of ethnoracial minoritized populations persists in studies examining psychedelic therapies, despite growing calls for diversity. Non-Hispanic White participants remain an over-represented majority by a large margin, though, there were greater proportions of ethnic minoritized populations included in studies since 2018, particularly in studies conducted in the USA. This indicates progress towards equity in psychedelic research, though much work is needed to inform the safety and efficacy of psychedelic treatments in the general population. There was no funding source for this study.

society is an important but complex task for research. We know from other research on social identity that respondents are likely to report problems and coping strategies that are acceptable...

Over the last decade, the United Kingdom has invested significant resources in its clinical trial infrastructure. Clinical research networks have been formed, and some general oversight functions for clinical research have been centralised. One of the initiatives is a registration programme for Clinical Trials Units involved in the coordination of clinical trials. An international review panel of experts in clinical trials has been convened for three reviews over time, reviewing applications from Clinical Trials Units in the United Kingdom. The process benefited from earlier work by the National Cancer Research Institute that developed accreditation procedures for trials units involved in cancer trials. This article describes the experience with the three reviews of UK Clinical Trials Units which submitted applications. This article describes the evolution and impact of this registration process from the perspective of the current international review panel members, some of whom have served on all reviews, including two done by the National Cancer Research Institute. Applications for registration were invited from all active, non-commercial Clinical Trials Units in the United Kingdom. The invitations were issued in 2007, 2009 and 2012, and applicants were asked to describe their expertise and staffing levels in specific areas. To ensure that the reviews were as objective as possible, a description of expected core competencies was developed and applicants were asked to document their compliance with meeting these. The review panel assessed each Clinical Trials Unit against the competencies. The Clinical Trials Unit registration process has evolved over time with each successive review benefiting from what was learned in earlier ones. The review panel has seen positive changes over time, including an increase in the number of units applying, a greater awareness on the part of host institutions about the trials activity within their organisations, more widespread development of Standard Operating Procedures in key areas and improvements in information technology systems used to host clinical trials databases. Key funders are awarding funds only to registered units, and host institutions are implementing procedures and structures to ensure improved communication between all parties involved in trials within their organisation. The registration process developed in the United Kingdom has helped to ensure that trials units in the United Kingdom are compliant with regulatory standards and can meet acceptable standards of quality in their conduct of clinical trials. There is an increased awareness among funders, host institutions and Clinical Trials Units themselves of the required competencies, and communication between all those involved in trials has increased. The registration process is an effective and financially viable way of ensuring that objective standards are met at a national level.

Psychedelic medicine is an emerging field of research and practice that examines the psychotherapeutic effects of substances classified as hallucinogens on the human mind, body, and spirit. Current research explores the safety and efficacy of these substances for mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although current studies explore psychotherapeutic effects from a biomedical perspective, gaps in awareness around cultural issues in the therapeutic process are prominent. African Americans have been absent from psychedelic research as both participants and researchers, and little attention has been paid to the potential of psychedelics to address traumas caused by racialization. This paper examines cultural themes and clinical applications from the one-time use of 3,4-methylenedioxymethamphetamine (MDMA) as part of an US Food and Drug Administration (FDA)-approved clinical trial and training exercise for three African American female therapists. The primary themes that emerged across the varied experiences centered on strength, safety, connection, and managing oppression/racialization. The participants' experiences were found to be personally meaningful and instructive for how Western models of psychedelic-assisted psychotherapy could be more effective and accessible to the Black community. Included is a discussion of the importance of facilitator training to make best use of emerging material when it includes cultural, racial, and spiritual themes. A lack of knowledge and epistemic humility can create barriers to treatment for underserved populations. Implications for future research and practice for marginalized cultural groups are also discussed, including consideration of Functional Analytic Psychotherapy (FAP) as an adjunct to the psychedelic-therapy approaches currently advanced. As women of color are among the most stigmatized groups of people, it is essential to incorporate their perspectives into the literature to expand conversations about health equity.

Ketamine is a prescription drug used for general anesthesia. In subanesthetic doses, it induces profound psychedelic experiences and hallucinations. The subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in the authors' use of ketamine-assisted psychotherapy for alcoholism. The results of a controlled clinical trial demonstrated a considerable increase in efficacy of the authors' standard alcoholism treatment when supplemented by ketamine psychedelic therapy (KPT). Total abstinence for more than one year was observed in 73 out of Ill (65.8%) alcoholic patients in the KPT group, compared to 24% (24 out of 100 patients) of the conventional treatment control group (p<0.01). The authors' studies of the underlying psychological mechanisms of KPT have indicated that ketamine-assisted psychedelic therapy of alcoholic patients induces a harmonization of the Minnesota Multiphasic Personality Inventory (MMPI) personality profile, positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to various aspects of self and other people, positive changes in life values and purposes. important insights into the meaning of life and anincrease in the level of spiritual development. Most importantly, these psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations showed that the phannacological action of KPT affects both monoaminergic and opioidergic neurotransmitter metabolism, i.e., those neurochemical systems which are involved in the pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis demonstrated that ketamine increases theta activity in cerebrocortical regions of alcoholic patients. This is evidence of the reinforcement of limbic cortex interaction during the KPT session.

Background Recent years have seen renewed clinical interest in the therapeutic potential of classical psychedelics, such as psilocybin, LSD, DMT, and mescaline. While modern studies have focused on adult populations, adolescents under 18 are routinely excluded due to regulatory, legal, and ethical challenges. Although there exists observational data and historical studies from 1959 to 1974 focusing on persons under 18, these earlier trials do not meet contemporary scientific and ethical standards. Hence, despite growing interest in the intersection of adolescent mental health and psychedelic therapy, it is unclear whether any controlled clinical research has been conducted with adolescents in the 21st century. To address this gap, we intend to conduct a scoping review of clinical studies involving psychedelic drug administration, including psychedelic-assisted therapy, in adolescent populations. The present contribution is a protocol for this scoping review. Methods Our scoping review will adhere to the methodological framework of Arksey &amp; O’Malley (2005), which involves five stages: (1) identifying the research question, (2) developing the search strategy, (3) setting inclusion criteria, (4) extracting data, and (5) presenting and analysing the results. We will include both peer-reviewed sources and study protocols that explicitly present evidence of an interventional study involving the administration of psychedelic drugs to adolescents under the age of 18 in the years 2000 - present. We will search for relevant studies in Pubmed (includes MEDLINE), EMBASE, APA PsycInfo, Cochrane Review Library, Web of Science, Cumulated Index to Nursing and Allied Health Literature (CINAHL) and Google Scholar. Clinical trial registers will also be searched, including the USA-based ClinicalTrials.gov and other global registers. Two raters will independently assess articles for eligibility, with disagreements to be resolved by a third reviewer. Data from eligible articles will be charted using a standardized data extraction form. The data will be reported following PRISMA-ScR guidelines.

Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and faecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this guideline paper, we discuss the key considerations that affect the gut microbiome of animal and clinical studies assessing renal function, many which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatisation, baseline microbiota and its normalisation, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardising study designs, methods and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.

Research of psychedelic assisted therapies is at an all-time high, though few studies highlight extra-pharmacological factors that may affect treatment efficacy. One critical set of attributes includes the therapeutic setting itself, which describe the physical and socio-cultural environments in which the drug-assisted session occurs. Despite enduring consensus of the influence of setting, recommendations for establishing and reporting key setting variables remain sparse across clinical trial protocols and published research methodologies. The purpose of this paper is to: (1) present what is known of the influence and implications of setting to psychedelic-assisted therapies, with a particular focus on 3,4-methylenedioxymethamphetamine (MDMA); and (2) propose a set of reporting guidelines for operationalizing and reporting key setting variables in clinical trials of psychedelic-assisted therapies, based on recommendations emerging from clinical trials of MDMA for PTSD. In fact, recommendations should be expanded to “set” - the subject's mood, expectations, and broader psychological condition - once this is more fully developed in the field. The proposed reporting guidelines offer a means of increasing the volume and variability of data necessary for future empirical examination of key setting attributes influencing treatment efficacy, while preserving practitioner and patient autonomy to co-construct adaptive therapy settings according to their respective needs and expertise.

Using GFR, Albuminuria, and Their Changes in Clinical Trials and Clinical Care

BackgroundThe publication of the United Kingdom (UK) Standards for Public Involvement (PI) (UK Standards) in research drew a clear line in the sand regarding the importance of utilising the unique experience, skills and expertise that lay people may offer to the development, conduct and dissemination of clinical research. The UK Standards provide a benchmark which researchers should aim to achieve, yet its implementation continues to be a step wise iterative process of change management. A recent evaluation by a regional research group has suggested that our understanding of PI is enhanced through reflection on the UK Standards. We report on the utility of PI in the design, conduct and dissemination of the HIDDen study, a national, multicentre clinical study based across three UK centres.MethodsA retrospective review of PI within the HIDDen study was conducted using field notes taken by the lead author from interactions throughout their involvement as a lay representative on the study. Key members of the HIDDen study were interviewed and data analysed to explore adherence to the UK Standards.ResultsThere was universal support for PI across the study management group with genuine inclusivity of lay members of the committee. All six of the UK Standards were met to varying degrees. The greatest opportunities lay in ‘working together’ and ‘support and learning’. There were challenges meeting ‘governance’ with evidence of participation in decision making but less evidence of opportunities in management, regulation, leadership.ConclusionThis study concurs with previous research supporting the utility of the Standards in the conduct and evaluation of PI in clinical research. To our knowledge this is the first multi-national study to be evaluated against the UK Standards.

Gene Therapy for Cancer