Fast and sensitive UHPLC-MS/MS analysis of cannabinoids and their acid precursors in pharmaceutical preparations of medical cannabis and their metabolites in conventional and non-conventional biological matrices of treated individual.

Monitoring pharmacological active compounds in pharmaceutical preparations of medical cannabis and in conventional and non-conventional biological matrices of treated individuals use requires both a wide linear range and sensitive detection. We have developed and validated a fast and sensitive method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for analysis of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA-A) and cannabidiolic acid (CBDA) and some major metabolites of THC such as 11-nor-9-carboxy-THC (THC-COOH), 11-hydroxy-THC (11-OH-THC), Δ-9-THC-Glucuronide (THC-GLUC) and THC-COOH-Glucuronide (THC-COOH-GLUC) in conventional (whole blood and urine) and non-conventional (oral fluid and sweat) of individual treated with medical cannabis preparation. Specifically, THC, THCA-A, CBD and CBD-A were determined in cannabis decoction and oil prepared to treat individuals. The method used positive electrospray ionization (ESI) mode to reach the sensitivity needed to detect minimal amounts of analytes under investigations exposure with limits of quantification ranging from 0.2 to 0.5 ng per milliliter (ng/mL) or ng per patch in case of collected sweat. The validation results indicated this method was accurate (average inter/intra-day error, <10%), precise (inter/intra-day imprecision, <10%), and fast (10 min run time). In addition, time-consuming sample preparation was avoided applying dilute and shoot procedure, meeting the needs for potential large-scale population studies. The analysis of real samples demonstrated a pharmacokinetics of cannabinoids, their precursors and their metabolites dependent from quantity of carboxylated and decarboxylated compounds in pharmaceutical preparations.

Public health implications of legalising the production and sale of cannabis for medicinal and recreational use.

We assess the current and describe possible future public health impacts of the legalisation of cannabis production, sale, and use in the Americas. First, we describe global patterns of cannabis use and their most probable adverse health effects. Second, we summarise evidence regarding the effectiveness of cannabinoids for medicinal use and describe approaches that have been used to regulate the use of medicinal cannabis and how these approaches might have affected medicinal and recreational use and harms (eg, road crashes). Third, we describe how jurisdictions that have legalised recreational use have regulated production and sale of cannabis. Fourth, we evaluate the effects of cannabis legalisation on cannabis use and harms and on the use of alcohol, tobacco, and other drugs. Fifth, we use alcohol and tobacco policy examples to identify possible long-term public health effects of cannabis legalisation. Finally, we outline policy approaches that could minimise harms to public health arising from the legalisation of a commercial cannabis industry.

Cannabis-based medicines for chronic pain management: current and future prospects.

PURPOSE OF REVIEW: The medicinal use of cannabis has recently become the focus of much medical, as well as political, attention. This reality of growing use but limited evidence creates unique dilemmas for the prescribing clinician. The purpose of this review is to explore current evidence and gaps in knowledge and offer some practical considerations. RECENT FINDINGS: There is robust preclinical data regarding the relevance of the endocannabinoid system to many pain-relevant processes. However, evidence to support cannabis-based medicines clinical use is still lacking. The best evidence to date is in managing neuropathic pain, although whether effects are clinically significant remains undetermined. However, the safety profile of cannabinoids seems favorable, especially by comparison to other medications used for pain control. SUMMARY: The endocannabinoid system is undoubtedly a new and exciting pharmaceutical target for chronic pain management, but transition from preclinical to clinical studies has so far proved difficult. Although it is reasonable to consider cannabinoids for otherwise unresponsive pain, care should be taken in frail clinical populations. As this has become a socioeconomic and political issue in which agendas often take precedence over due diligence, there is a pressing need for unbiased empirical data and high quality evidence to better inform prescribers and patients.

Decision Models for Assessing the Cost Effectiveness of Treatments for Pediatric Drug-Resistant Epilepsy: A Systematic Review of Economic Evaluations.

BACKGROUND: Drug-resistant epilepsy affects about one-third of children with epilepsy and is associated with high costs to the healthcare system, yet the cost effectiveness of most treatments is unclear. Use of cannabis-based products for epilepsy is increasing, and the cost effectiveness of such strategies relative to conventional pharmacologic treatments must be considered. OBJECTIVE: The objective of this systematic review was to identify economic evaluations of cannabis-based treatments for pediatric drug-resistant epilepsy. We also sought to identify and appraise decision models that have been used in economic evaluations of pharmacologic treatments (i.e., antiepileptic drugs) in this population. METHODS: Electronic searches of MEDLINE, EMBASE, and the Cochrane library, as well as a targeted grey literature search, were undertaken (11 June 2018). Model-based full economic evaluations involving cannabis-based treatments or pharmacologic treatments for drug-resistant epilepsy in children were eligible for inclusion. Two independent reviewers selected studies for inclusion, and study quality was assessed by use of the Drummond and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. Study findings, as well as model characteristics, are narratively summarized. RESULTS: Nine economic evaluations involving children with drug-resistant epilepsy were identified; however, none involved cannabis-based treatments. All studies involved pharmacologic treatments compared with other pharmacologic treatments or non-pharmacologic treatments (i.e., ketogenic diet, epilepsy surgery, vagus nerve stimulation). Few studies have assessed the cost effectiveness of pharmacologic treatments in specific drug-resistant epilepsy syndromes, including Dravet and Lennox-Gastaut syndromes. Five included studies involved use of Markov models with a similar structure (i.e., health states based on seizure frequency relative to baseline). There was a wide range of methodological quality, and few studies fully addressed context-specific issues such as weight gain and treatment switching. CONCLUSION: Whether cannabis-based treatments for pediatric drug-resistant epilepsy represent good value for money has yet to be investigated. Economic evaluations of such treatments are needed and should address issues of particular importance in pediatric epilepsy, including weight gain over time, switching or discontinuation of treatments, effectiveness of interventions and comparators, and long-term effectiveness beyond the duration of available clinical studies. PROSPERO REGISTRATION: CRD42018099591.

Recreational marijuana legalization and prescription opioids received by Medicaid enrollees.

OBJECTIVES: Medical marijuana use may substitute prescription opioid use, whereas nonmedical marijuana use may be a risk factor of prescription opioid misuse. This study examined the associations between recreational marijuana legalization and prescription opioids received by Medicaid enrollees. METHODS: State-level quarterly prescription drug utilization records for Medicaid enrollees during 2010-2017 were obtained from Medicaid State Drug Utilization Data. The primary outcome, opioid prescriptions received, was measured in three population-adjusted variables: number of opioid prescriptions, total doses of opioid prescriptions in morphine milligram equivalents, and related Medicaid spending, per quarter per 100 enrollees. Two difference-in-difference models were used to test the associations: eight states and DC that legalized recreational marijuana during the study period were first compared among themselves, then compared to six states with medical marijuana legalized before the study period. Schedule II and III opioids were analyzed separately. RESULTS: In models comparing eight states and DC, legalization was not associated with Schedule II opioid outcomes; having recreational marijuana legalization effective in 2015 was associated with reductions in number of prescriptions, total doses, and spending of Schedule III opioids by 32% (95% CI: (-49%, -15%), p = 0.003), 30% ((-55%, -4.4%), p = 0.027), and 31% ((-59%, -3.6%), p = 0.031), respectively. In models comparing eight states and DC to six states with medical marijuana legalization, recreational marijuana legalization was not associated with any opioid outcome. CONCLUSIONS: No evidence suggested that recreational marijuana legalization increased prescription opioids received by Medicaid enrollees. There was some evidence in some states for reduced Schedule III opioids following the legalization.

Structural barriers in access to medical marijuana in the USA-a systematic review protocol.

BACKGROUND: There are 43 state medical marijuana programs in the USA, yet limited evidence is available on the demographic characteristics of the patient population accessing these programs. Moreover, insights into the social and structural barriers that inform patients' success in accessing medical marijuana are limited. A current gap in the scientific literature exists regarding generalizable data on the social, cultural, and structural mechanisms that hinder access to medical marijuana among qualifying patients. The goal of this systematic review, therefore, is to identify the aforementioned mechanisms that inform disparities in access to medical marijuana in the USA. METHODS: This scoping review protocol outlines the proposed study design for the systematic review and evaluation of peer-reviewed scientific literature on structural barriers to medical marijuana access. The protocol follows the guidelines set forth by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist. DISCUSSION: The overarching goal of this study is to rigorously evaluate the existing peer-reviewed data on access to medical marijuana in the USA. Income, ethnic background, stigma, and physician preferences have been posited as the primary structural barriers influencing medical marijuana patient population demographics in the USA. Identification of structural barriers to accessing medical marijuana provides a framework for future policies and programs. Evidence-based policies and programs for increasing medical marijuana access help minimize the disparity of access among qualifying patients.