The implications of the use of cannabidiol-related products in a safety-sensitive drug testing environment: A medical-legal perspective.

Cannabis access laws allow for the use of cannabis in private and the trade, purchase and use of hemp-related products as a complementary medicine and for other benefits. Cannabidiol (CBD) has the treatment potential for several conditions but, with the lack of resources in South Africa to maintain the legislation, products contaminated with delta-9-tetrahydrocannabinol (Δ9-THC) are sold by some suppliers who do not comply with the legislative provisions in terms of the threshold concentrations for Δ9-THC. This dilemma complicates a medical review officer's decision regarding intentional use of Δ9-THC or otherwise, since a CBD user may have purchased the product legally and in good faith. Hemp- and CBD-containing products were analysed by gas chromatography-mass spectrometry and compliance was assessed for CBD and Δ9-THC purity against the legislative thresholds. A strategy based on metabolite ratios is suggested to distinguish between intentional or irresponsible cannabis use and legitimate CBD use.

An Ethical Framework to Manage Patient Requests for Medical Marijuana.

An increasing number of states are legalizing marijuana use for medicinal purposes despite marijuana use remaining criminalized at the federal level and continued Schedule I status by the US Food and Drug Administration. Many of those states in which medical marijuana is legal require physician involvement to facilitate patient access. In addition, physicians may have ethical objections to medical marijuana use or may not believe there is adequate scientific evidence to support its use. The constellation of these factors creates an ethical quandary for physicians when approached by patients for assistance in accessing medical marijuana. This article provides an ethical framework that provides guidance to physicians in managing these patient requests taking into consideration the above ethically relevant factors.

Kratom: Implications for Health Care Providers.

Kratom is an herbal drug originating from the Mitragyna speciosa, a plant indigenous to Southeast Asia. Kratom has been widely used for its stimulant and opioid-like effects derived from its main psychoactive alkaloid properties mitragynine and 7-hydroxymitragynine. In the United States, kratom is gaining popularity as an herbal and natural dietary supplement, as well as a natural and legal alternative to narcotics. Kratom use is typically accompanied by increasing tolerance and dependence making it highly problematic. Kratom's potentially toxic and lethal properties have become an emerging public health threat. Due to deficiencies of governmental controls and its rising prevalence among individuals who ingest kratom, health care providers need to be familiar with the pharmacology, adverse effects, and problems associated with kratom ingestion when caring for individuals. [Journal of Psychosocial Nursing and Mental Health Services, 57(12), 15-20.].

Cannabis and Health Research: Rapid Progress Requires Innovative Research Designs.

The United States has witnessed enormous changes concerning the acceptance of medicinal and recreational cannabis use. Sixty-three percent of the US population has access to medicinal cannabis markets, which offer increasingly diverse and potent cannabis products. Considering the rapidly changing cultural, political, and legal landscape, the scientific literature does not adequately inform public policy, medical decision making, or harm reduction approaches. The goals of this paper are to (1) investigate the state of cannabis research on medical conditions commonly treated with cannabis, (2) review the barriers that have led to large gaps between cannabis use and available empirical data, and (3) suggest a path forward with new research designs to address these gaps. Thus, we aim to advance a more nuanced understanding of the barriers to cannabis research and suggest innovative research designs necessary for rapid development of a meaningful knowledge base.

Regulatory aspects of quality and safety for live recombinant viral vaccines against infectious diseases in Japan.

Recombinant viral vaccines expressing antigens of pathogenic microbes (e.g., HIV, Ebola virus, and malaria) have been designed to overcome the insufficient immune responses induced by the conventional vaccines. Our knowledge of and clinical experience with the new recombinant viral vaccines are insufficient, and a clear regulatory pathway is needed for the further development and evaluation of recombinant viral vaccines. In 2018, the research group supported by the Ministry of Health, Labour and Welfare, Japan (MHLW) published a concept paper to address the development of recombinant viral vaccines against infectious diseases. Herein we summarize the concept paper-which explains the Japanese regulatory concerns about recombinant viral vaccines-and provide a focus of discussion about the development of recombinant viral vaccines.

Kratom policy: The challenge of balancing therapeutic potential with public safety.

Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.

The Surprising Reach of FDA Regulation of Cannabis, Even After Descheduling.

As more states legalize cannabis, the push to "deschedule" it from the Controlled Substances Act is gaining momentum. At the same time, the Food and Drug Administration (FDA) recently approved the first conventional drug containing a cannabinoid derived from cannabis­cannabidiol (CBD) for two rare seizure disorders. This would all seem to bode well for proponents of full federal legalization of medical cannabis. But some traditional providers are wary of drug companies pulling medical cannabis into the regular small molecule drug development system. The FDA's focus on precise analytical characterization and on individual active and inactive ingredients may be fundamentally inconsistent with the "entourage effects" theory of medical cannabis. Traditional providers may believe that descheduling cannabis would free them to promote and distribute their products free of federal intervention, both locally and nationally. Other producers appear to assume that descheduling would facilitate a robust market in cannabis-based edibles and dietary supplements. In fact, neither of these things is true. If cannabis were descheduled, the FDA's complex and comprehensive regulatory framework governing foods, drugs, and dietary supplements would preclude much of this anticipated commerce. For example, any medical claims about cannabis would require the seller to complete the rigorous new drug approval process, the cost of which will be prohibitive for most current traditional providers. Likely also unexpected to some, there is no pathway forward for conventional foods containing cannabis constituents, with the (probably exclusive) exception of certain hemp seed ingredients, if those foods cross state lines. And it will certainly come as a shock to many that federal law already prohibits the sale of dietary supplements containing CBD--including those already on the market as well as those made from "hemp," which has recently been descheduled under the 2018 Farm Bill. This Article describes in detail the surprising reach of the FDA and then outlines three modest, but legal, pathways forward for cannabis-based products in a world where cannabis has been descheduled.

Prevalence and correlates of medical cannabis patients' use of cannabis for recreational purposes.

BACKGROUND: Rates of legal medical cannabis (MC) use are increasing, but little is known about the prevalence and correlates of recreational cannabis (RC) use among medical users (MC/R). METHODS: 348 MC users who resided in a state in which MC is legal and had medical authorization to use MC legally completed an anonymous survey in Spring 2017 (64.1% female, 82.8% White, mean age 33.03[±10.37] years). Rates of endorsing MC/R and the following potential correlates of MC/R were examined: the legal status of RC in participants' states of residence, sex, age, race, primary medical condition, MC product(s) used, MC expectancies, features of MC sought out (e.g., high tetrahydrocannabinol [THC] content), and negative cannabis use consequences. RESULTS: 55.5% of MC users engaged in MC/R. MC/R was associated with residing in a state in which RC is legal, being female, using MC for pain or mental health conditions, vaping MC concentrates, holding positive expectancies for combustible MC, and seeking out MC products with high THC concentrations. Preferring MC products with high cannabidiol (CBD) concentrations protected against MC/R. CONCLUSIONS: More than half of MC users endorsed MC/R, which is considerably higher than rates of misuse observed for other prescription medications. Findings raise concerns about circumvention of RC laws in states where RC remains illegal and could be used to inform MC regulatory efforts (e.g., reducing THC content, increasing CBD content). Findings also suggest that prevention/intervention efforts to reduce MC/R are needed, especially among high-risk populations of MC users (e.g., women, pain patients, psychiatric patients).

FDA regulatory approach to steviol glycosides.

Stevia rebaudiana (Bertoni) Bertoni, commonly known as stevia, is a plant native to South America that has been cultivated for hundreds of years. In 1995, FDA revised its import alert on stevia leaves and extracts to allow for their use as dietary ingredients in dietary supplements. In 2007, the Joint FAO/WHO Expert Committee on Food Additives established a safe level of intake and specifications for steviol glycosides that included a minimum purity of 95% of seven named steviol glycosides. In 2008, FDA responded without questions to a Generally Recognized as Safe (GRAS) notice for the use of highly purified steviol glycosides obtained from stevia leaves as a general purpose sweetener in food. Due to the existing import alert, FDA filed, evaluated, and has not objected to more than 50 GRAS notices for the use of various high-purity steviol glycosides as sweeteners in food. In this paper, we highlight FDA's practices for filing and evaluating GRAS notices for steviol glycosides. We also provide a summary of the data and information presented in GRAS notices for steviol glycosides in the GRAS Notification program. FDA has received a new wave of GRAS notices that include alternative biotechnological methods for production of steviol glycosides.

Rhetorical and regulatory boundary-work: The case of medical cannabis policy-making in Israel.

Recent studies have explored how professionals draw boundaries to reach workable solutions in conflictual and contested areas. Yet they neglected to explore the relationships and dynamics between how boundaries are demarcated in rhetoric and in policy. This article examines these relationships empirically through the case of medical cannabis (MC) policy-making in Israel. Drawing on interviews with key stakeholders in the MC policy field, formal policy documents, and observations of MC conferences, this article sheds light on the dynamics between rhetorical boundary-work and what we term regulatory boundary-work, namely setting rules and regulations to demarcate boundaries in actual practice. Results show how certain definitions of and rationales for a discursive separation between "medical" and "recreational" cannabis and between cannabis "medicalization" and "legalization" prevailed and were translated into formal policy, as well as how stakeholders' reactions to this boundary-work produced policy changes and the shifting of boundaries. Both rhetorical and regulatory boundary-works emerge as ongoing contested processes of negotiation, which are linked in a pattern of reciprocal influence. These processes are dominated by certain actors who have greater power to determine how and why specific boundaries should be drawn instead of others.

Medical cannabis legalization and opioid prescriptions: evidence on US Medicaid enrollees during 1993-2014.

BACKGROUND AND AIMS: While the United States has been experiencing an opioid epidemic, 29 states and Washington DC have legalized cannabis for medical use. This study examined whether state-wide medical cannabis legalization was associated with reduction in opioids received by Medicaid enrollees. DESIGN: Secondary data analysis of state-level opioid prescription records from 1993-2014 Medicaid State Drug Utilization Data. Linear time-series regressions assessed the associations between medical cannabis legalization and opioid prescriptions, controlling for state-level time-varying policy covariates (such as prescription drug monitoring programs) and socio-economic covariates (such as income). SETTING: United States. PARTICIPANTS: Drug prescription records for patients enrolled in fee-for-service Medicaid programs that primarily provide health-care coverage to low-income and disabled people. MEASUREMENTS: The primary outcomes were population-adjusted number, dosage and Medicaid spending on opioid prescriptions. Outcomes for Schedule II opioids (e.g. hydrocodone, oxycodone) and Schedule III opioids (e.g. codeine) were analyzed separately. The primary policy variable of interest was the implementation of state-wide medical cannabis legalization. FINDINGS: For Schedule III opioid prescriptions, medical cannabis legalization was associated with a 29.6% (P = 0.03) reduction in number of prescriptions, 29.9% (P = 0.02) reduction in dosage and 28.8% (P = 0.04) reduction in related Medicaid spending. No evidence was found to support the associations between medical cannabis legalization and Schedule II opioid prescriptions. Permitting medical cannabis dispensaries was not associated with Schedule II or Schedule III opioid prescriptions after controlling for medical cannabis legalization. It was estimated that, if all the states had legalized medical cannabis by 2014, Medicaid annual spending on opioid prescriptions would be reduced by 17.8 million dollars. CONCLUSION: State-wide medical cannabis legalization appears to have been associated with reductions in both prescriptions and dosages of Schedule III (but not Schedule II) opioids received by Medicaid enrollees in the United States.

The ascent of the blessed: regulatory issues on health effects and health claims for probiotics in Europe and the rest of the world.

The outcome of the first series of health claim applications for probiotics in Europe as evaluated by the European Food Safety Authority (EFSA) has, up to 2013 almost completely yielded negative results. All recent applications also have been rejected, including the latest on prevention of mastitis in breastfeeding mothers. In other developed countries, such as Switzerland, Japan and Canada, the health effects of probiotics, for which scientific evidence has been provided, can be communicated to potential consumers. The number of clinical trials with probiotics over recent years shows a trend to level off or even decline. At the same time, clinical research into the role of (gut) microbiota in a wide variety of diseases and conditions is booming. Ultimately, this may offer new indications for gut microbiota management by probiotics, prebiotics or other food supplements.

The Scheduling of Kratom and Selective Use of Data.

Kratom is a traditional drug from Southeast Asia that has been an emerging new substance in the United States. On August 30, 2016, the DEA announced the intention to emergency schedule kratom into Schedule I. To support this decision, the DEA cited an increase in drug seizures of kratom and an increase in calls to poison control concerning kratom. However, a short time later, on October 12, 2016, the DEA withdrew the intent to schedule kratom after public and congressional backlash. The withdrawal by the DEA was somewhat unprecedented. To better understand both decisions, the current article examines the evidence the DEA cited to support their decision to emergency schedule kratom and the degree and type of media coverage of kratom to determine if a media-driven drug panic occurred.

Complementary medicines: When regulation results in revolution.

Medicines have evolved over time and so has the realisation of the importance of quality control and regulatory processes. The regulatory practices include all the steps from the development and manufacture of the active ingredients until the medicines reach the consumer. The Medicines Control Council (MCC) is mandated to regulate medicines in South Africa. Complementary medicines were previously perceived to be unregulated, although the Medicines Act does not distinguish between allopathic and complementary medicine. As the era of unregulated complementary medicine ended, the requirements in terms of dossier content left many role-players at odds. However, the MCC has a mandate to ensure that the registration of a medicine is in the interest of the public and that complementary medicine is manufactured in a facility adhering to good manufacturing practice, according to which efficacy and safety are supported by reliable data with a known shelf-life.

Regulation of Controlled Substance Prescribing: An Overview for Certified Nurse-Midwives and Certified Midwives.

In addition to the regulation of prescriptive authority and prescribing practices conducted by individual states, the prescription of controlled substances is also regulated at the federal level by the US Drug Enforcement Administration (DEA). While there are variations in state laws relative to controlled substance prescribing, federal law is uniform across states as established by the Controlled Substances Act (21 United States Code § 801-890) and the DEA Regulations (Title 21, Code of Federal Regulations). The only controlled substance for which states have authorized use that is outside the regulations set forth in the Controlled Substances Act is marijuana for the treatment of certain medical conditions. A review of statutes and administrative rules for all 50 states and the District of Columbia revealed that certified midwives (CMs) are authorized to prescribe controlled substances only in the state of New York, and there are variations across states in the regulation of controlled substance prescribing by certified nurse-midwives (CNMs). The purpose of this article is to examine the federal regulation of controlled substance prescribing by the US DEA and common variations in state regulations relative to controlled substance prescribing.