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Rationale: Cannabidiol (CBD) products lacking regulatory approval are being used to self-treat a myriad of conditions and for their unsubstantiated health benefits. The scientific evidence supporting these claims largely arises not from controlled clinical trials, but from the recognition that CBD has numerous biological targets. Yet, CBD is commonly consumed and often in over-the-counter products that are unapproved and of unknown composition. Epidiolex® is the only product that has undergone rigorous pharmacokinetic assessment and testing in clinical trials; it was approved as a non-scheduled drug by the U.S. Food and Drug Administration for the treatment of intractable childhood-onset seizures. However, studies investigating CBD for other medical conditions are limited in number and often lack the scientific rigor, controls, or sample sizes required to draw clinically meaningful conclusions. Although Epidiolex® is safe for human consumption, recent changes in regulation of commercially available CBD products have resulted in limited quality control and products marketed with unknown CBD bioavailability. Even scientifically rigorous studies have used different sources of CBD and different suspension vehicles for administration, making it difficult to compare results among studies and resolve mixed outcomes., Objectives: This paper reviews the molecular targets, pharmacokinetics, and safety and abuse liability of CBD; additionally, the extant evidence on its potential therapeutic effects for neurological disorders, pain, inflammation, conditions related to immune function, psychiatric disorders, and substance use are described.

Rationale: As a species, humans are vulnerable to numerous mental disorders, including depression and schizophrenia. This susceptibility may be due to the evolution of our large, complex brains, or perhaps because these illnesses counterintuitively confer some adaptive advantage. Additionally, cultural and biological factors may contribute to susceptibility and variation in mental illness experience and expression. Taking a holistic perspective could strengthen our understanding of these illnesses in diverse cultural contexts., Objectives: This paper reviews some of these potential factors and contextualizes mental disorders within a biocultural framework., Results: There is growing evidence that suggests cultural norms may influence inflammation, neurotransmitters, and neurobiology, as well as the illness experience. Specific examples include variation in schizophrenia delusions between countries, differences in links between inflammation and emotion between the United States and Japan, and differences in brain activity between Caucasian and Asian participants indicating that cultural values may moderate cognitive processes related to social cognition and interoception., Conclusions: Research agendas that are grounded in an appreciation of biocultural diversity as it relates to psychiatric illness represent key areas for truly interdisciplinary research that can result in culturally sensitive treatments and highlight possible biological variation affecting medical treatment.

Background and Rationale: Cathinones are amphetamine analogues that produce stimulant effects with rewarding properties. For many decades, synthetic cathinones have been used in the United States (USA) for abuse purposes, leading to concern about public safety by the federal government. Under the Controlled Substances Act (CSA), the federal government may place drugs with high abuse potential but no currently accepted medical use into Schedule I of the CSA. The process of scheduling an abusable drug involves both the Department of Health and Human Services (HHS), through the Food and Drug Administration (FDA) and the National Institute on Drug Abuse (NIDA), and the Department of Justice, through the Drug Enforcement Administration (DEA)., Results: This paper details how numerous synthetic cathinones were placed under CSA control between 1973 and 2018, with an emphasis on 10 cathinones that were placed into Schedule I in 2017 (butylone, naphyrone, pentylone, pentedrone, 3-fluoro-N-methylcathinone (FMC), 4-FMC, 4-methyl-N-ethylcathinone, 4-methyl-pyrrolidinopropiophenone, alpha-pyrrolidinobutiophenone, and α-pyrrolidinopentiophenone). A summary is provided of the scientific and medical analysis performed by HHS, in the form of an Eight-Factor Analysis (8FA), as prescribed by the CSA. This 8FA was then evaluated and signed by the Assistant Secretary for Health at HHS and transmitted to DEA, which permanently placed the 10 cathinones into Schedule I after public notices were published into the Federal Register., Discussion and Conclusions: Understanding the scientific data, analysis, and complex process utilized by the US federal government in the CSA scheduling of cathinones with abuse potential and no accepted medical use is important for transparency in governmental decision-making.

Human research with hallucinogens such as lysergic acid diethylamide (LSD) has been ongoing in the USA since 1949. During the 1960s, LSD was investigated for a variety of psychiatric indications, including the following: as an aid in treatment of schizophrenia; as a means of creating a "model psychosis"; as a direct antidepressant; and as an adjunct to psychotherapy. Studies with all drugs, including LSD, have always been conducted under federal regulatory controls, including the 1938 Food Drug and Cosmetic Act (FDCA; which ensured the safety of drugs) and the 1962 Kefauver-Harris Amendments to the FDCA (which described appropriate scientific methodology and ensured drug efficacy). This paper details how the 1962 Amendments introduced numerous safety and efficacy requirements that must be in satisfied during clinical drug research-and how human studies conducted with LSD in the 1960s struggled with their fulfillment. Information is provided from Senate hearings, case law, and interviews with key investigators. Examples are also drawn from scientific papers and symposia published during and since that period, with a focus on information from clinical studies conducted with LSD by psychiatrist Albert Kurland at the Spring Grove State Hospital, near Baltimore, MD. While Kurland largely conformed with these new regulations, other investigators often fell short of complying with scientific standards and federal requirements. Thus, the human hallucinogen studies of the 1960s are best understood as providing pilot data on safety and efficacy, as well as testable hypotheses for current hallucinogen studies conducted under modern scientific and regulatory standards.

Rationale: Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer's perspective will help to forge a better alliance between participants and researchers., Objective: Participant satisfaction is seldom assessed in pharmacological research. In this paper, we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior., Method: Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures., Results: Ninety-six (95.0%) parents returned the questionnaire. Of these, 80.0 to 96.8%, depending on the question, expressed satisfaction with their child's research participation regardless of treatment outcome or assignment to active drug or placebo. In all, 90.5% of parents indicated that they would "definitely" recommend the clinical trial to other families with similar children. A total of 92.7% indicated that they would rejoin the clinical trial if they had to do it all over again. Ethnic minority subjects were more satisfied than white participants with the use of "learning tests"., Conclusions: Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures. Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views. Further satisfaction studies of this sort are encouraged.

Rationale: This article is intended to explore how minority status and cultural factors affect the participation of subjects in clinical psychopharmacology research., Objectives and Methods: A literature review was performed using key words "clinical psychopharmacology trials", "psychiatric ethics" and "minority groups". Major goals of this review were to examine current knowledge base and identify existing gaps in this fairly new area of psychiatric research., Results: We found extremely few papers addressing the issue directly. Most references to minority groups were made peripherally, and many of these were extrapolated to psychiatric patients from work done on medical populations. We found no empirical studies done in psychiatric populations., Conclusions: Systematic, well-designed research studies are needed to elucidate how culture, race and ethnicity impact on such issues as accrual, retention, informed consent and safeguards against the potential exploitation of minority research subjects. On the basis of the literature review and our personal experience doing clinical research with minority patients, we provide several recommendations and specific suggestions to clinical researchers who include minority patients in their clinical trials.

Rationale: There is a broad range of complex ethical issues in the conduct of psychopharmacological drug studies that go beyond the question of the ethics of placebo controls. However, our empirical knowledge with respect to these issues is very limited. This review, although not exhaustive, highlights an array of ethical issues that arose from discussions within the NIMH Human Subjects Research Council Workgroup., Objectives: To delineate issues in psychopharmacological drug studies that require debate and would benefit from research leading to the development of empirically-supported guidelines., Methods: Information included in this report was drawn from the first author's participation as chair of the NIMH Human Subjects Research Council Workgroup, guidelines for the ethical conduct of research proposed by professional organizations to which the first and third author belong, and relevant research literature., Results: We have focused on general issues relating to informed consent, research with special populations, and long-term treatment studies. Additionally, we raise issues relevant to large research-oriented institutions., Conclusions: The essential ethical challenge in psychopharmacological trials is to balance risks and benefits in the context of the needs and capacities of individual research subjects. The IRB system must become evidence-based and not rely on unproven assumptions. Specific research studies should be undertaken to address many of the issues of informed consent and research ethics postulated in this paper.