Emergency use authorization medication distribution, utilization, and monitoring in a national integrated healthcare system.

PURPOSE: The purpose of this project was to develop and optimize a dashboard and registry to manage the distribution, utilization, and monitoring of coronavirus disease 2019 (COVID-19) emergency use-authorized medications (CEUAMs). SUMMARY: CEUAMs have specific requirements that must be met for prescribing, monitoring, and compliance. When remdesivir, the first COVID-19 medication with emergency use authorization (EUA), was approved, it immediately became necessary for the Veterans Health Administration, a national integrated health system, to describe the requirements for EUA, to distribute the medication in a fair and equitable manner, and to ensure compliance with all EUA requirements. A dashboard was developed and iteratively updated as additional CEUAMs were approved. The dashboard tracked CEUAM distribution and monitoring at the national, regional, facility, and patient level. Par stock levels were initially determined at the national level. Facilities were also able to request an additional allotment of medication based on demand and allocated supplies from the Department of Health and Human Services. Providers completed a questionnaire for the CEUAM for each patient to ensure all requirements for the medication were met. If there were data integrity concerns, the entry was flagged for review at the facility level and, upon evaluation, corrections were made. CONCLUSION: Development of the dashboard was resource intensive but provided an excellent mechanism to share information among facilities and national offices. Other healthcare systems can develop similar dashboards to ensure appropriate use of CEUAMs for their patients while meeting all CEUAM requirements.

Complementary and alternative therapies in the palliative setting.

Complementary and alternative medicine (CAM) encompasses a wide range of medication, herbal, dietary and physical therapies that are not usually considered within the realm of conventional therapeutics. Approximately two thirds of the Australian population use CAMs and only around half of this number will discuss their use of these products with their doctor. Clinical use is commonly seen in patients with life-limiting illness, often because they experience a high burden of symptoms. However, it is also the case that many of these therapies do not have demonstrated efficacy, particularly for the often broad list of conditions and symptoms for which they are chosen to be used. Further, depending on whether they are sold as medications, sold as food supplements or imported illegally and distributed via nonstandard therapeutic channels, several products have had reports of toxicity, severe adverse effects, batch irregularities and drug interactions with other therapies. This awareness, together with lack of standardisation of products and lack of interchangeability between brands has made prescribers unwilling to put patients at risk of harm by supporting their use. In this article, we cover general pharmacological principles around use of a small selection of chemicals used in a medical setting to enable some guidance for use.

Liver abscess microbiota of feedlot steers finished in natural and traditional management programs.

Liver abscess etiology in feedlot steers involves the escape of bacteria from the digestive tract to form a polymicrobial abscess within or on the external surface of the liver. However, little is known about the effects of feedlot finishing systems on the microbial composition of the liver abscess purulent material. Liver abscesses were collected at the time of harvest from steers originating from a single feedlot managed in either a traditional program (which included tylosin phosphate supplementation) or a natural program (without tylosin phosphate supplementation). The purulent material of liver abscesses from traditionally managed steers (N = 53 abscesses) and that of naturally managed steers (N = 62 abscesses) was characterized using the V4 region of the 16S rRNA gene. Two phyla and three genera were found in greater than 1% relative abundance across all abscesses. The genus Fusobacterium was identified in all liver abscess samples and accounted for 64% of sequencing reads. Bacteroides and Porphyromonas genera accounted for 33% and 1% of reads, respectively. Trueperella was more likely to be found in the liver abscesses of naturally managed steers than traditionally managed steers (P = 0.022). Over 99% of the genus-level bacterial sequences observed across all liver abscesses belonged to Gram-negative genera. Bacteria known to colonize both the rumen and hindgut were identified within liver abscesses. No differences in alpha diversity or beta diversity were detected between liver abscess communities (between the two management programs or individual pens) when tested as richness, Shannon Diversity Index, or weighted UniFrac distances (P > 0.05). These results were consistent with previous identification of Fusobacterium necrophorum as the primary bacteriologic agent within liver abscesses and emphasized the relationship between the gastrointestinal microbiota and liver abscess formation. Though the microbiota of the liver abscess purulent material was similar between steers fed an antibiotic-free diet and those fed an antibiotic-containing diet from the same feedlot, divergence was detected in liver abscess communities with some being dominated by Fusobacterium and others being dominated by Bacteroides.

As feedlot cattle consume grain, the rumen becomes more acidic. If the lining of the digestive tract is damaged, bacteria that normally remain in the digestive tract can enter the body. Certain bacteria like Fusobacterium necrophorum are involved in the formation of liver abscesses. Feedlot cattle are commonly fed an antibiotic (tylosin phosphate) to reduce the occurrence of liver abscesses, but increasing scrutiny is placed on the antibiotic use. However, the effect of eliminating the antibiotic used to prevent liver abscesses on the bacterial communities involved in liver abscess formation is unknown. This study compared the bacteria found within liver abscesses of cattle fed tylosin phosphate with that of cattle not fed tylosin phosphate. All liver abscesses contained F. necrophorum, and Bacteroides was the second most commonly identified bacterium. Trace amounts of bacteria known to colonize the mouth and digestive tract were observed. Trueperella, a bacteria targeted by tylosin phosphate, was found more frequently in liver abscesses from cattle that received no antibiotic. While the core bacterial composition of the liver abscess was unaffected by antibiotic supplementation to feedlot steers, reduced Trueperella in liver abscesses from cattle-fed tylosin phosphate could be related to a reduction in liver abscess prevalence.

Integrated Digital Health System Tools to Support Decision Making and Treatment Preparation in CKD: The PREPARE NOW Study.

RATIONALE & OBJECTIVE: Digital health system tools to support shared decision making and preparation for kidney replacement treatments for patients with chronic kidney disease (CKD) are needed. STUDY DESIGN: Descriptive study of the implementation of digital infrastructure to support a patient-centered health system intervention. SETTING & PARTICIPANTS: 4 CKD clinics within a large integrated health system. EXPOSURE: We developed an integrated suite of digital engagement tools to support patients' shared decision making and preparation for kidney failure treatments. Tools included an automated CKD patient registry and risk prediction algorithm within the electronic health record (EHR) to identify and prioritize patients in need of nurse case management to facilitate shared decision making and preparation for kidney replacement treatments, an electronic patient-facing values clarification tool, a tracking application to document patients' preparation for treatments, and an EHR work flow to broadcast patients' treatment preferences to all health care providers. OUTCOMES: Uptake and acceptability. ANALYTIC APPROACH: Mixed methods. RESULTS: From July 1, 2017, through June 30, 2018, the CKD registry identified 1,032 patients in 4 nephrology clinics, of whom 243 (24%) were identified as high risk for progressing to kidney failure within 2 years. Kidney Transitions Specialists enrolled 117 (48%) high-risk patients by the end of year 1. The values tool was completed by 30/33 (91%) patients who attended kidney modality education. Nurse case managers used the tracking application for 100% of patients to document 287 planning steps for kidney replacement therapy. Most (87%) high-risk patients had their preferred kidney replacement modality documented and displayed in the EHR. Nurse case managers reported that the tools facilitated their identification of patients needing support and their navigation activities. LIMITATIONS: Single institution, short duration. CONCLUSIONS: Digital health system tools facilitated rapid identification of patients needing shared and informed decision making and their preparation for kidney replacement treatments. FUNDING: This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (IHS-1409-20967). TRIAL REGISTRATION: ClinicalTrials.gov NCT02722382.

The Veterans Administration and Department of Defense clinical practice guidelines for the diagnosis and management of sleep disorders: what does this mean for the practice of sleep medicine?

In 2017 the Veterans Administration (VA) and Department of Defense (DOD) launched development of clinical practice guidelines (CPGs) for the diagnosis and treatment of sleep disorders, with the goal of informing and improving patient care. The guideline development process followed GRADE methodology, considering studies and systematic reviews published over the 10-year period prior to guideline development. A total of 41 recommendations were made,18 related to the diagnosis and treatment of obstructive sleep apnea (OSA) and 23 regarding chronic insomnia disorder. In contrast to other published guidelines, the VA DoD CPGs provide a comprehensive approach to diagnosis and management of the two most common sleep disorders, including a discussion of the sequencing of diagnostic approaches and treatment options. Regarding OSA, strong recommendations were made for follow-up evaluation after non-diagnostic home sleep apnea tests, positive airway pressure therapy as first-line treatment, and the incorporation of supportive, educational and behavioral interventions for patients at high risk for PAP therapy non-adherence due to comorbid conditions. Strong recommendations were also made for the use of cognitive-behavioral therapy for insomnia and against the use of kava (an herbal supplement) in the treatment of chronic insomnia disorder. These guidelines, while intended to directly inform care within VA and DOD, are broadly relevant to the practice of sleep medicine. The majority of scientific evidence was based on studies of non-military, non-veteran populations. The CPG is a major milestone for the VA and DOD in recognizing the importance of evidence-based treatments for sleep disorders in military personnel and veterans.

Rapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiLX).

A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low affinity to their target. Herein, we describe an analysis using X-ray crystallography of a diverse library of compounds prepared using microscale parallel synthesis. This approach yielded an 8-fold increase in affinity and detailed structural information for the resulting complex, providing an efficient and broadly applicable approach to early fragment development.

Translational hurdles with cannabis medicines.

PURPOSE: Internationally, there has been widespread medical use of cannabis medicines before rigorous evaluations in randomised controlled trials (RCTs). Some advocates of medicinal use of cannabis argue that real-world evidence (RWE) can be a substitute for or at least supplement evidence from RCTs. We explore the utility, limitations and impact of RWE in the translation of cannabis medicines research into clinical practice using the established literature. METHODS: A literature search was performed via Embase and Medline using a diverse range of cannabinoid and RWE search terms. The review provides a snapshot of cannabis medicine RWE initiatives from around the world. RESULTS: Diverse and novel sources of real-world data and RWE include international cannabis registries, surveys, post-marketing data collection and use of electronic or digital health records. The strengths and limitations of using RWE in translational research are highlighted, along with the identification of barriers to RCTs involving cannabis medicines. CONCLUSIONS: RWE promises to play a significant role in the evaluation of cannabis medicines around the world. When used appropriately RWE may complement RCT data by providing valuable insights into cannabis medicine safety and effectiveness. TAKE HOME MESSAGES: It is important that real-world evidence (RWE) is used to complement rather than replace randomised controlled trial (RCT) evidence on cannabis medicines. Technological advances have created the opportunity to explore diverse and novel sources of cannabis medicine RWE. Although RWE may be more reflective of real-world clinical practice, it cannot provide conclusive evidence of the safety and efficacy of cannabis medicines. While acknowledging its limitations, RWE may nonetheless provide some guidance on safety and adverse events of cannabis medicines. RWE has already had a significant impact on the regulation of cannabis medicines.

Exploration, Explanation, and Parent-Child Interaction in Museums.

Young children develop causal knowledge through everyday family conversations and activities. Children's museums are an informative setting for studying the social context of causal learning because family members engage together in everyday scientific thinking as they play in museums. In this multisite collaborative project, we investigate children's developing causal thinking in the context of family interaction at museum exhibits. We focus on explaining and exploring as two fundamental collaborative processes in parent-child interaction, investigating how families explain and explore in open-ended collaboration at gear exhibits in three children's museums in Providence, RI, San Jose, CA, and Austin, TX. Our main research questions examined (a) how open-ended family exploration and explanation relate to one another to form a dynamic for children's learning; (b) how that dynamic differs for families using different interaction styles, and relates to contextual factors such as families' science background, and (c) how that dynamic predicts children's independent causal thinking when given more structured tasks. We summarize findings on exploring, explaining, and parent-child interaction (PCI) styles. We then present findings on how these measures related to one another, and finally how that dynamic predicts children's causal thinking. In studying children's exploring we described two types of behaviors of importance for causal thinking: (a) Systematic Exploration: Connecting gears to form a gear machine followed by spinning the gear machine. (b) Resolute Behavior: Problem-solving behaviors, in which children attempted to connect or spin a particular set of gears, hit an obstacle, and then persisted to succeed (as opposed to moving on to another behavior). Older children engaged in both behaviors more than younger children, and the proportion of these behaviors were correlated with one another. Parents and children talked to each other while interacting with the exhibits. We coded causal language, as well as other types of utterances. Parents' causal language predicted children's causal language, independent of age. The proportion of parents' causal language also predicted the proportion of children's systematic exploration. Resolute behavior on the part of children did not correlate with parents' causal language, but did correlate with children's own talk about actions and the exhibit. We next considered who set goals for the play in a more holistic measure of parent-child interaction style, identifying dyads as parent-directed, child-directed, or jointly-directed in their interaction with one another. Children in different parent-child interaction styles engaged in different amounts of systematic exploration and had parents who engaged in different amounts of causal language. Resolute behavior and the language related to children engaging in such troubleshooting, seemed more consistent across the three parent-child interaction styles. Using general linear mixed modeling, we considered relations within sequences of action and talk. We found that the timing of parents' causal language was crucial to whether children engaged in systematic exploration. Parents' causal talk was a predictor of children's systematic exploration only if it occurred prior to the act of spinning the gears (while children were building gear machines). We did not observe an effect of causal language when it occurred concurrently with or after children's spinning. Similarly, children's talk about their actions and the exhibit predicted their resolute behavior, but only when the talk occurred while the child was encountering the problem. No effects were found for models where the talk happened concurrently or after resolving the problem. Finally, we considered how explaining and exploring related to children's causal thinking. We analyzed measures of children's causal thinking about gears and a free play measure with a novel set of gears. Principal component analysis revealed a latent factor of causal thinking in these measures. Structural equation modeling examined how parents' background in science related to children's systematic exploration, parents' causal language, and parent-child interaction style, and then how those factors predicted children's causal thinking. In a full model, with children's age and gender included, children's systematic exploration related to children's causal thinking. Overall, these data demonstrate that children's systematic exploration and parents' causal explanation are best studied in relation to one another, because both contributed to children's learning while playing at a museum exhibit. Children engaged in systematic exploration, which supported their causal thinking. Parents' causal talk supported children's exploration when it was presented at certain times during the interaction. In contrast, children's persistence in problem solving was less sensitive to parents' talk or interaction style, and more related to children's own language, which may act as a form of self-explanation. We discuss the findings in light of ongoing approaches to promote the benefit of parent-child interaction during play for children's learning and problem solving. We also examine the implications of these findings for formal and informal learning settings, and for theoretical integration of constructivist and sociocultural approaches in the study of children's causal thinking.

Using Therapeutic Drug Monitoring and Pharmacovigilance to Overcome Some of the Challenges of Developing Medicinal Cannabis from Botanical Origins.

PURPOSE: Plants belonging to the genus Cannabis have been domesticated and used by humans for millennia. Thought to have originated from central Asia, cannabis has been harnessed for its nutritional, therapeutic, and psychoactive properties, and as a source of fiber (Office of Medicinal Cannabis. Analytical Monograph Cannabis Flos. Den Haag, The Netherlands: Office of Medicinal Cannabis; 2014). Human use of cannabis is not novel; however, its medicalization offers a new pharmacotherapeutic frontier. METHODS: The authors recently reported a systematic review of the contaminants of cannabis (National Academies of Sciences Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC; 2017). This article draws on the research limitations identified by that review and examines a collection of the relevant literature to provide an appreciation of the current evidence base. RESULTS: The review explores the current status of cannabis in medical use, the drug development aspects that apply when taking a plant through to pill development, and the roles that therapeutic drug monitoring and pharmacovigilance have to guide practice until the drug development information on medicinal cannabis preparations is complete. CONCLUSIONS: A surge of public and clinical interest in the possible therapeutic applications of constituent cannabinoids has potentiated global legislative and policy reform. However, our understanding of its properties, optimized use, and harmful effects remains incomplete (Therapeutic Goods Administration. Guidance for the use of medicinal cannabis in Australia In: Department of Health Department, editor. Woden ACT Australian Government 2017; Dryburgh LM, Bolan NS, Grof CP, Galettis P, Schneider J, Lucas CJ, et al. Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Brit J Clin Pharm. 2018;84(11):2468-2476). In particular, a comprehensive appreciation of its toxicity profile is lacking.

Investigation of tylosin in feed of feedlot cattle and effects on liver abscess prevalence, and fecal and soil microbiomes and resistomes1.

Liver abscesses in feedlot cattle are detrimental to animal performance and economic return. Tylosin, a macrolide antibiotic, is used to reduce prevalence of liver abscesses, though there is variable efficacy among different groups of cattle. There is an increased importance in better understanding the etiology and pathogenesis of this condition because of growing concern over antibiotic resistance and increased scrutiny regarding use of antibiotics in food animal production. The objective of this study was to compare the microbiomes and antimicrobial resistance genes (resistomes) of feces of feedlot cattle administered or not administered tylosin and in their pen soil in 3 geographical regions with differing liver abscess prevalences. Cattle (total of 2,256) from 3 geographical regions were selected for inclusion based on dietary supplementation with tylosin (yes/no). Feces and pen soil samples were collected before harvest, and liver abscesses were identified at harvest. Shotgun and 16S rRNA amplicon sequencing were used to evaluate the soil and feces. Microbiome and resistome composition of feces (as compared by UniFrac distances and Euclidian distances, respectively) did not differ (P > 0.05) among tylosin or no tylosin-administered cattle. However, feedlot location was associated with differences (P ≤ 0.05) of resistomes and microbiomes. Using LASSO, a statistical model identified both fecal and soil microbial communities as predictive of liver abscess prevalence in pens. This model explained 75% of the variation in liver abscess prevalence, though a larger sample size would be needed to increase robustness of the model. These data suggest that tylosin exposure does not have a large impact on cattle resistomes or microbiomes, but instead, location of cattle production may be a stronger driver of both the resistome and microbiome composition of feces.

Uncured-Labeled Meat Products Produced Using Plant-Derived Nitrates and Nitrites: Chemistry, Safety, and Regulatory Considerations.

Consumers often malign conventional curing agents while concomitantly accepting the natural forms of the same constituents in numerous food products. This paradox ostensibly exceeds all other food-related controversies to date and likely contributes to the rapid expansion of meat products that utilize natural nitrate derivatives. While there is high demand for these products, a fundamental lack of understanding regarding the safety and chemical implications of curing agents, whether derived from synthetic or natural sources, continues to persist. This manuscript elucidates the variations among curing preparations with particular emphasis pertaining to the associated safety, chemical, and regulatory ramifications encompassing these product categories.

Use of multidomain management strategies by community dwelling adults with chronic pain: evidence from a systematic review.

Background and aims Multidomain strategies (i.e. two or more strategies) for managing chronic pain are recommended to avoid excessive use of opioids while producing the best outcomes possible. The aims of this systematic review were to: 1) determine if patient-reported pain management is consistent with the use of multidomain strategies; and 2) identify the role of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) in patient-reported pain management. Methods Bibliographic databases, websites, and reference lists of included studies were searched to identify published articles reporting community-based surveys of pain self-management from January 1989 to June 2017 using controlled vocabulary (and synonyms): pain; self-care; self-management; self-treatment; and adult. Two independent reviewers screened studies and extracted data on subject demographics, pain characteristics, pain self-management strategies, and pain outcomes. Pain self-management strategies were organized according to our conceptual model. Included studies were assessed for risk of bias. Differences between the researchers were resolved by consensus. Results From the 3,235 unique records identified, 18 studies published between 2002 and 2017 from 10 countries were included. Twenty-two types of pharmacological strategies were identified (16 prescription, six non-prescription). NSAIDs (15 studies, range of use 10-72%) and opioids (12 studies, range of use 5-72%) were the most commonly reported prescription pharmacological strategies. Other prescription pharmacological strategies included analgesics, acetaminophen, anticonvulsants, antidepressants, anxiolytics, salicylates, ß-blockers and calcium channel blockers, disease-modifying anti-rheumatic drugs and steroids, muscle relaxants, topical products, triptans, and others. Twenty-two types of non-pharmacological strategies were identified: four medical strategies (10 studies), 10 physical strategies (15 studies), four psychological strategies (12 studies), and four self-initiated strategies (15 studies). Medical strategies included consulting a medical practitioner, chiropractic, and surgery. Physical strategies included exercise, massage, hot and cold modalities, acupuncture, physical therapy, transcutaneous electrical nerve stimulation, activity modification or restriction, assistive devices, and altering body position/posture. Psychological strategies included relaxation, prayer or meditation, therapy, and rest/sleep. Self-initiated strategies included dietary or herbal supplements, dietary modifications, and complementary and alternative medicine. Overall, the number of strategies reported among the studies ranged from five to 28 (out of 44 identified strategies). Limited data on pain outcomes was reported in 15 studies, and included satisfaction with pain management strategies, pain interference on daily activities, adverse events, lost work or restricted activity days, emergency department visits, and disabilities. Conclusions A wide variety and large number of pharmacological and non-pharmacological strategies to manage chronic pain were reported, consistent with the use of multidomain strategies. High levels of use of both NSAIDs and opioids also were reported. Implications Comprehensive review and consultation with patients about their pain management strategies is likely needed for optimal outcomes. Additional research is needed to determine: how many, when, and why multidomain strategies are used; the relationship between opioid use, multidomain management strategies, and level of pain; how multidomain strategies relate to outcomes; and if adding strategies to a pain management plan increases the risk of adverse events or interactions, and increases an individuals pain management burden.

Emerging Adjunctive Approach for the Treatment of Sepsis: Vitamin C and Thiamine.

Evidence is emerging that parenteral administration of high-dose vitamin C and thiamine may be a beneficial adjuvant therapy of severe sepsis and septic shock. Despite modern practices in critical care medicine, sepsis and severe sepsis remain a leading cause of morbidity and mortality in the critical care unit.

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects.

There has been a resurgence in interest and use of the cannabis plant for medical purposes. However, an in-depth understanding of plant contaminants and toxin effects on stability of plant compounds and human bioavailability is needed. This systematic review aims to assess current understanding of the contaminants of cannabis and their effect on human health, leading to the identification of knowledge gaps for future investigation. A systematic search of seven indexed biological and biomedical databases and the Cochrane library was undertaken from inception up to December 2017. A qualitative synthesis of filtered results was undertaken after independent assessment for eligibility by two reviewers. The common cannabis contaminants include microbes, heavy metals and pesticides. Their direct human toxicity is poorly quantified but include infection, carcinogenicity, reproductive and developmental impacts. Cannabis dosing formulations and administration routes affect the transformation and bioavailability of contaminants. There may be important pharmacokinetic interactions between the alkaloid active ingredients of cannabis (i.e. phytocannabinoids) and contaminants but these are not yet identified nor quantified. There is significant paucity in the literature describing the prevalence and human impact of cannabis contaminants. Advances in the availability of cannabis globally warrant further research in this area, particularly when being used for patients.

Gaps in predicting clinical doses for cannabinoids therapy: Overview of issues for pharmacokinetics and pharmacodynamics modelling.

Model-based prediction on clinical doses for cannabinoids therapy is beneficial in the clinical setting, especially for seriously ill patients with both altered pharmacokinetics and pharmacodynamic responses. The objective of this article is to review the currently available PK and/or PD models of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and to highlight the major issues for modelling this complex therapeutic area. A systematic search was conducted in the electronic databases PubMed and EMBASE using the key words 'cannabis', 'cannabinoid', 'tetrahydrocannabinol', 'THC', 'cannabidiol', 'CBD', 'pharmacokinetic model', 'pharmacodynamics model' and their combinations. Twelve empirical PK and/or PD models for THC for humans were identified. Among them, ten were developed from data of healthy participants and two were from ill patients. Models for CBD were not found. Model-based prediction on appropriate doses for cannabinoids therapy for ill patients is currently limited due to insufficiency of relevant PK and PD data. High-quality PK and PD data of cannabinoids for patients with different illnesses is needed for model development. Mechanism-based PK and PD models are promising for improved predictive dosing performance for ill and comorbid patients.

Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement.

ABSTRACT: The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown. Dronabinol is not approved by the United States Food and Drug Administration (FDA) for treatment of OSA, and medical cannabis and synthetic extracts other than dronabinol have not been studied in patients with OSA. The composition of cannabinoids within medical cannabis varies significantly and is not regulated. Synthetic medical cannabis may have differential effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine (AASM) that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety. OSA should be excluded from the list of chronic medical conditions for state medical cannabis programs, and patients with OSA should discuss their treatment options with a licensed medical provider at an accredited sleep facility. Further research is needed to understand the functionality of medical cannabis extracts before recommending them as a treatment for OSA.

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.

Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.

Introduction: Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use. Materials and Methods: Eighteen regular cannabis users participated in an ∼10-week open-label pragmatic trial involving daily oral administration of 200 mg CBD, with no change to their ongoing cannabis use requested. Participants were assessed at baseline and post-CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields. Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen's d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users. Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer's disease, and major depressive disorder).