The Therapeutic Potential of Psilocybin.

The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the "hippie" counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.

Icosapent ethyl: scientific and legal controversies.

Icosapent ethyl (Vascepa) is a purified preparation of the omega-3 fatty acid eicosapentaenoic acid, which is marketed by Amarin Pharma based in Ireland. The product was initially approved by the US Food and Drug Administration for the use of a high dose (4 g/day) in the treatment of hypertriglyceridaemia. On the basis of the results of the REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl Intervention Trial), the agency later granted a label extension to include the additional indication of a reduction in risk of cardiovascular events in persons with serum triglyceride levels of 150 mg/dL or greater and established cardiovascular disease or diabetes. Data supporting the efficacy of omega-3 fatty acids in the prevention of cardiovascular disease have been inconsistent and controversial. The story of the development of icosapent ethyl has been fraught with challenges, including the invalidation of six core patents on the product, and recently, the completion of a new clinical trial, STRENGTH (Long-Term Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia), that directly contradicts REDUCE-IT and calls into question whether icosapent ethyl is actually effective in the secondary prevention of cardiovascular events. This article traces the course of the development of this fascinating product and discusses its complex medical, regulatory and legal history, which is still continuing to unfold.

Probiotics and the Microbiome-How Can We Help Patients Make Sense of Probiotics?

The notion of probiotics as microbes that confer health benefits has its origins in the speculative ideas that are more than a century old, yet remain largely unsubstantiated by scientific evidence. The recent advances in microbiome science have highlighted the importance of intestinal microbes in human physiology and disease pathogenesis. These developments have provided a boost to the probiotics industry, which continues to experience exponential growth driven mainly by creative marketing. Consumers, patients, and most health care providers are not able to discern the underlying science or differentiate the permitted claims that promise vague health benefits from disease-specific claims reserved for drugs. No probiotic product has been able to satisfy the regulatory requirements to be categorized as a drug, a substance intended to cure, mitigate, or prevent disease. However, patients take probiotic products in the belief that they will help to treat their intestinal or systemic diseases. Thus far, the regulators have failed to create policies that would assist to inform the public in this area. In fact, the existing regulatory regime actually creates formidable barriers to research that could provide evidence for clinical efficacy of probiotic products. We propose a potential solution to this vexing problem, where a committee created through a partnership of academia, professional organizations, and industry, but free of potential conflicts of interest, would be charged with rigorous evaluation of specific probiotic products and the evidence in support of their different claims. Companies that would submit to this process would earn the trust of consumers and healthcare providers, as well as a distinction in the marketplace.

Nationwide Actions Against Heart Failure Pandemic in Japan　- What Should We Do From Academia?

Heart failure pandemic is rapidly approaching in Japan, requiring nationwide actions. In particular, the Japanese Circulation Society and related societies launched the Stroke and Cardiovascular Disease Control Act, which was passed by the National Diet, as the first ever legislative policy measure against stroke and cardiovascular disease. In association with this, actions against heart failure pandemic from the scientific field are also important. Because heart failure pandemic is a critical problem not only in Japan but also in many developed countries, we believe the nationwide approach, as summarized here, will greatly contribute to the development of cardiovascular medicine, particularly the management and treatment of heart failure worldwide.

An IQ Consortium Perspective on The Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on the Need for Nonhuman Primates in Biomedical Research, Production and Testing of Products and Devices (Update 2017).

The recent Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on "The need for nonhuman primates in biomedical research, production and testing of products and devices" (2017 SCHEER) highlights approaches that could significantly contribute to the replacement, reduction, and refinement of nonhuman primate (NHP) studies. Initiatives that have the potential to affect NHP welfare and/or their use are expected to be appropriate, fair, and objective and publicly disseminated information focused on NHPs in biomedical research, which includes toxicologic and pathologic research and testing, should be objectively evaluated by stakeholder scientists, researchers, and veterinarians. Thus, IQ Consortium member companies convened to develop an informed and objective response, focusing on identifying areas of agreement, potential gaps, or missing information in 2017 SCHEER. Overall, the authors agree that many positions in the 2017 SCHEER Opinion generally align with industry views on the use of NHPs in research and testing, including the ongoing need of NHPs in many areas of research. From the perspective of the IQ Consortium, there are several topics in the 2017 SCHEER that merit additional comment, attention, or research, as well as consideration in future opinions.

[The Japanese legal system and the applicability of laws and regulations on private information protection and research ethics relating to medical research].

Objectives　To clarify the structure, applicability, and objectives of the current Japanese legislation for private information protection and research ethics and to examine the clauses of the related laws/regulations for academic research purposes.Methods　The research design is a descriptive study based on a systematic literature review. Using the "e-Gov" database, the laws/regulations relating to private information protection and research ethics that apply to medical research involving human subjects and human genome/gene analysis research were included in the research. The Drugs Law (Law No. 145 of 1960) and related GCP/GPSP regulations and laws/regulations on administrative organizations, management, and procedures were excluded. Furthermore, the guidelines and Q&A relating to these laws/regulations and all 47 prefectural regulations on private information protection have been selected from the websites of the related ministries, government organizations, and prefectures.Results　Our study demonstrated that the current legal system on private information protection consists of three layers and that the applicability of the laws/regulations in this area varies according to the type of research organization. Additionally, the applicability of the laws/regulations on research ethics is different depending on the research area. While the Private Information Protection Law (PIPL) for the private sector contains two objectives, PIPL for administrative organizations and PIPL for independent administrative organizations both include three objectives. For academic research purposes, PIPL for the private sector sets out a holistic exemption clause, whereas the other two PIPLs stipulate three specific exemption clauses. Furthermore, our research revealed that the clauses of the prefectural regulations demonstrated many variances.Conclusion　This study suggests that the current Japanese legal system relating to private information protection could be defined as a "mixed model," wherein the laws/regulations concerned are not necessarily consistent. The protection of medical information is solely regulated by a few specific laws with a narrow scope of application; the ethical guidelines are not directly based on any laws; and identifying applicable laws/regulations, depending on the category of research organization, is complicated, especially in the case of collaborative research involving researchers from various organizations. Therefore, in the larger framework of legislation, it is indispensable to reconsider the protection of private medical information and its effective use, including the ethics of this process because of the sensitive and useful nature of private medical information.

Dietary Supplements: Regulatory Challenges and Research Resources.

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them.

Researching the Appropriateness of Care in the Complementary and Integrative Health Professions Part 2: What Every Researcher and Practitioner Should Know About the Health Insurance Portability and Accountability Act and Practice-based Research in the United States.

OBJECTIVE: This paper describes a process for ensuring and documenting Health Insurance Portability and Accountability Act (HIPAA) compliance in clinical practice-based research. METHODS: The Center of Excellence for Research in Complementary and Alternative Medicine was funded by National Center for Complementary and Integrative Health to develop the methods for researching the appropriateness of care in complementary and integrative health, which previously was known as complementary and alternative medicine. We recruited 125 participating chiropractic clinics for enrolling patients and gathering their data via the online surveys. Chiropractic clinics completed the following: (1) obtained the files of patients who provided prior consent (the prospective sample), (2) obtained the files of the patients selected randomly using specified randomization procedures (the retrospective sample), and (3) transferred all patient data to the RAND Corporation via an encrypted file. RESULTS: Most of the doctors of chiropractic from clinical practices had no concerns about obtaining and transferring the files of patients who provided informed consent. However, some doctors were uneasy about allowing the researchers to access the randomly selected files of patients who had not provided prior authorization. This led us to develop a set of forms to provide clinics about HIPAA compliance. CONCLUSION: For this study, we provided clinics with information about the rules under HIPAA, demonstrated how the study complied with those rules, explained the logic behind the necessity for collecting files from both the prospective and retrospective samples, and, if requested, provided clinics with a confidentiality agreement signed by the study principal investigator and an organizational contracts representative. The process we developed may assist other complementary and integrative health researchers and practitioners in future studies.

Liver injury from herbal and dietary supplements.

Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373).

Advancing probiotic research in humans in the United States: Challenges and strategies.

This is a summary from a workshop convened as part of the 13(th) annual meeting of the International Scientific Association for Probiotics and Prebiotics. A group of 24 stakeholders, including clinical experts, researchers, federal government officials, funding agencies, lawyers and industry experts met to review the challenges of the current regulatory approach to human research on probiotics in the USA and to discuss ways to move research forward. There was agreement that some of the current regulatory requirements imposed on probiotic research in the United States hindered research progress and increased cost without improving study subject safety. Many situations were outlined by clinical investigators demonstrating the impact of regulatory delays on research progress. Additionally, research is compromised when study designs and outcomes require manipulation so as to invoke less burdensome regulatory requirements. These responses by investigators to regulatory requirements have placed United States' researchers at a disadvantage. The public ultimately suffer when research to clarify the role of these products on health is stalled. Workshop participants concurred that regulatory oversight should balance study subject vulnerability with documented safety for the intended use for the probiotic strain, and that human research on foods and supplements should not be be regulated as drug research. Challenges and potential improvement strategies are discussed.

[Analysis and discussion on current condition of acupuncture clinical research registration].

To introduce the international registration condition of acupuncture clinical research. With the examples of World Health Organization International Clinical Trials Registry Platform and the U. S. National Institutes of Health Clinical Registration Platform, the registration method and current condition of acupuncture clinical trials in international clinical trials registration platform were analyzed. The results indicate that the number of acupuncture clinical trials registration is gradually increased and the registration number from China is on the rise as well. But most domestic acupuncture clinical researches haven't been registered arid the researchers' valuing degree for clinical trials registration and methodology research needs to be improved.

Protecting Traditional Knowledge Related to Biological Resources: Is Scientific Research Going to Become More Bureaucratized?

For the past several decades, there has been a world debate on the need for protecting traditional knowledge. A global treaty appears to be a distant reality. Of more immediate concern are the steps taken by the global community to protect access to biological resources in the name of protecting traditional knowledge. The Indian experience with implementing the Convention on Biological Diversity has created substantial legal uncertainty in collaborative scientific research between Indians and foreigners apart from bureaucratizing the entire process of scientific research, especially with regard to filing of applications for intellectual property rights. The issue therefore is whether the world needs to better balance the needs of the scientific community with the rights of those who have access to traditional knowledge.

Illegal drugs laws: clearing a 50-year-old obstacle to research.

The United Nations drug control conventions of 1960 and 1971 and later additions have inadvertently resulted in perhaps the greatest restrictions of medical and life sciences research. These conventions now need to be revised to allow neuroscience to progress unimpeded and to assist in the innovation of treatments for brain disorders. In the meantime, local changes, such as the United Kingdom moving cannabis from Schedule 1 to Schedule 2, should be implemented to allow medical research to develop appropriately.

Plastic surgery practice models and research aims under the Patient Protection and Affordable Care Act.

As the health care landscape in the United States changes under the Affordable Care Act, providers are set to face numerous new challenges. Although concerns about practice sustainability with declining reimbursement have dominated the dialogue, there are more pressing changes to the health care funding mechanism as a whole that must be addressed. Plastic surgeons, involved in various practice models each with different relationships to hospitals, referring physicians, and payers, must understand these reimbursement changes to dictate adequate compensation in the future. In this article, the authors discuss bundle payments and accountable care organizations, and how plastic surgeons might best engage in these new system designs. In addition, the authors review the value of a focused and driven health-services research agenda in plastic surgery, and the importance of this research in supporting long-term financial stability for the specialty.