The effects of the 4/20 cannabis holiday and adult-use cannabis legalization on medical cannabis sales and medical cannabis patient registration in Arizona.

BACKGROUND: This study examined whether the 4/20 cannabis holiday was associated with increases in medical cannabis sales from licensed dispensaries in Arizona from 2018-2021, and whether adult-use cannabis legalization (the vote in November 2020 and retail sales in January 2021) was associated with declines in medical cannabis sales and in the number of registered medical patients. METHODS: Data came from the Arizona Medical Marijuana Program monthly reports from January 2018-December 2021. The reports show daily sales from licensed medical cannabis dispensaries (i.e., the number of medical cannabis dispensary transactions and the amount of cannabis sold in pounds), which we averaged by week, and show the number of registered medical cannabis patients each month. Autoregressive integrated moving average models were used to test changes in these outcomes associated with the 4/20 cannabis holiday and with legalization of adult-use cannabis. RESULTS: During the week of the 4/20 cannabis holiday, medical cannabis dispensary transactions abruptly increased by an average of 2,319.4 transactions each day (95% CI: 1636.1, 3002.7), and the amount of medical cannabis sold increased by an average of 120.3 pounds each day (95% CI: 99.3-141.3). During the first week of adult-use cannabis sales in late January 2021, medical cannabis dispensary transactions abruptly decreased by an average of 5,073 transactions each day (95% CI: -5,929.5, -4216.7), and the amount of medical cannabis sold decreased by an average of 119.1 pounds each day (95% CI: -144.2, -94.0). Moreover, medical cannabis sales continued to gradually decline each week after the start of adult-use retail sales, with declines in sales preceding declines in registered patients. By December 2021, slightly over a year after the vote to legalize adult-use cannabis, the actual number of registered medical cannabis patients fell short of the forecasted number, had adult-use not been legalized, by 36.5%. Moreover, the number of medical dispensary transactions and the amount of medical cannabis sold fell short of expectations, had adult-use cannabis not been legalized, by 58% and 53%, respectively. CONCLUSIONS: Findings document the blurred boundary between medical and non-medical cannabis use and are consistent with the possibility that medical cannabis legalization contributes to increases in adult cannabis use and dependence.

Principles of ideal diagnostic regulation and the IVDR.

This article discusses principles and concepts for ideal regulatory frameworks for diagnostics, and the expression of those principles in the EU IVDR. The authors present the benefits of regulatory frameworks and implementation approaches for diagnostics that are risk-based, globally convergent, connected, nimble and efficient, under the IVDR and with a future outlook. While many expressions of these principles can already be found in the EU IVDR text, and in its implementation approaches, their further embrace is needed in future EU diagnostic regulation. In the long term outlook, risk-based approaches can be extended to comprise entity-based excellence appraisals. Globally convergent approaches can be more explicit in e.g. qualification and classification of products. This will also help further reliance models. Better connections and cooperation between regulators across the healthcare spectrum including pharmaceuticals should be fostered. Nimble approaches such as Emergency Use Authorisations for pandemics are essential in highly regulated schemes like the IVDR and beyond. Finally, regulatory efficiency as in timely availability of IT infrastructure and oversight mechanisms is a distinguishing attribute of globally competitive diagnostic regulatory schemes. All the above needs consideration in the long term efforts to modernize the EU regulatory system, so that diagnostics can play their important role in clinical research as well as along the entire care continuum in the EU.

Too Important for the Bureaucrats: Rethinking Risk and Regulatory Presumptions in Times of Crisis.

The posture of American regulation of medicine is negative-we assume that a new drug is unsafe and ineffective until it is proven safe and effective.1 This regulatory posture is a heuristic normative principle, a specific instance of the so-called precautionary principle in public health law.2 It is defensible, if debatable, in many ordinary circumstances.3 But like many normative heuristics, this negative posture may compel suboptimal decision-making in emergencies, where context-specific decisions must be made and a range of unique values may apply.

The association between recreational cannabis legalization, commercialization and cannabis-attributable emergency department visits in Ontario, Canada: an interrupted time-series analysis.

BACKGROUND AND AIMS: Recreational cannabis was legalized in Canada in October 2018. Initially, the Government of Ontario (Canada's largest province) placed strict limits on the number of cannabis retail stores before later removing these limits. This study measured changes in cannabis-attributable emergency department (ED) visits over time, corresponding to different regulatory periods. DESIGN: Interrupted time-series design using population-level data. Two policy periods were considered; recreational cannabis legalization with strict store restrictions (RCL, 17 months) and legalization with no store restrictions [recreational cannabis commercialization (RCC), 15 months] which coincided with the COVID-19 pandemic. Segmented Poisson regression models were used to examine immediate and gradual effects in each policy period. SETTING: Ontario, Canada. PARTICIPANTS: All individuals aged 15-105 years (n = 13.8 million) between January 2016 and May 2021. MEASUREMENTS: Monthly counts of cannabis-attributable ED visits per capita and per all-cause ED visits in individuals aged 15+ (adults) and 15-24 (young adults) years. FINDINGS: We observed a significant trend of increasing cannabis-attributable ED visits pre-legalization. RCL was associated with a significant immediate increase of 12% [incident rate ratio (IRR) = 1.12, 95% confidence interval (CI) = 1.02-1.23] in rates of cannabis-attributable ED visits followed by significant attenuation of the pre-legalization slope (monthly slope change IRR = 0.98, 95% CI = 0.97-0.99). RCC and COVID-19 were associated with immediate significant increases of 22% (IRR = 1.22, 95% CI = 1.09-1.37) and 17% (IRR = 1.17, 95% CI = 1.00-1.37) in rates of cannabis-attributable visits and the proportion of all-cause ED visits attributable to cannabis, respectively, with insignificant increases in monthly slopes. Similar patterns were observed in young adults. CONCLUSIONS: In Ontario, Canada, cannabis-attributable emergency department visits stopped increasing over time following recreational cannabis legalization with strict retail controls but then increased during a period coinciding with cannabis commercialization and the COVID-19 pandemic.

Public Health Implications of Cannabis Legalization: An Exploration of Adolescent Use and Evidence-Based Interventions.

This article examines the relaxation of state marijuana laws, changes in adolescent use of marijuana, and implications for drug education. Under federal law, use of marijuana remains illegal. In spite of this federal legislation, as of 1 June 2021, 36 states, four territories and the District of Columbia have enacted medical marijuana laws. There are 17 states, two territories and the District of Columbia that have also passed recreational marijuana laws. One of the concerns regarding the enactment of legislation that has increased access to marijuana is the possibility of increased adolescent use of marijuana. While there are documented benefits of marijuana use for certain medical conditions, we know that marijuana use by young people can interfere with brain development, so increased marijuana use by adolescents raises legitimate health concerns. A review of results from national survey data, including CDC's YRBS, Monitoring the Future, and the National Household Survey on Drug Use, allows us to document changes in marijuana use over time. Increased legal access to marijuana also has implications for educational programming. A "Reefer Madness" type educational approach no longer works (if it ever did). We explore various strategies, including prevention programs for education about marijuana, and make recommendations for health educators.

Opioid use disorder and COVID-19: Implications for policy and practice.

ABSTRACT: Preliminary data suggest that opioid-related overdose deaths have increased subsequent to COVID-19. Despite national support for expanding the role of physician assistants (PAs) and NPs in serving patients with opioid use disorder, these clinicians are held to complex and stringent regulatory barriers. COVID-19 triggered significant changes from regulatory and federal agencies, yet disparate policies and regulations persist between physicians and PAs and NPs. The dual epidemics of COVID-19 and opioid use disorder highlight the inadequate infrastructure required to support patients, communities, and clinicians, and may serve as the catalyst for eliminating barriers to care.

Cannabis Legalization and Detection of Tetrahydrocannabinol in Injured Drivers.

BACKGROUND: The effect of cannabis legalization in Canada (in October 2018) on the prevalence of injured drivers testing positive for tetrahydrocannabinol (THC) is unclear. METHODS: We studied drivers treated after a motor vehicle collision in four British Columbia trauma centers, with data from January 2013 through March 2020. We included moderately injured drivers (those whose condition warranted blood tests as part of clinical assessment) for whom excess blood remained after clinical testing was complete. Blood was analyzed at the provincial toxicology center. The primary outcomes were a THC level greater than 0, a THC level of at least 2 ng per milliliter (Canadian legal limit), and a THC level of at least 5 ng per milliliter. The secondary outcomes were a THC level of at least 2.5 ng per milliliter plus a blood alcohol level of at least 0.05%; a blood alcohol level greater than 0; and a blood alcohol level of at least 0.08%. We calculated the prevalence of all outcomes before and after legalization. We obtained adjusted prevalence ratios using log-binomial regression to model the association between substance prevalence and legalization after adjustment for relevant covariates. RESULTS: During the study period, 4339 drivers (3550 before legalization and 789 after legalization) met the inclusion criteria. Before legalization, a THC level greater than 0 was detected in 9.2% of drivers, a THC level of at least 2 ng per milliliter in 3.8%, and a THC level of at least 5 ng per milliliter in 1.1%. After legalization, the values were 17.9%, 8.6%, and 3.5%, respectively. After legalization, there was an increased prevalence of drivers with a THC level greater than 0 (adjusted prevalence ratio, 1.33; 95% confidence interval [CI], 1.05 to 1.68), a THC level of at least 2 ng per milliliter (adjusted prevalence ratio, 2.29; 95% CI, 1.52 to 3.45), and a THC level of at least 5 ng per milliliter (adjusted prevalence ratio, 2.05; 95% CI, 1.00 to 4.18). The largest increases in a THC level of at least 2 ng per milliliter were among drivers 50 years of age or older (adjusted prevalence ratio, 5.18; 95% CI, 2.49 to 10.78) and among male drivers (adjusted prevalence ratio, 2.44; 95% CI, 1.60 to 3.74). There were no significant changes in the prevalence of drivers testing positive for alcohol. CONCLUSIONS: After cannabis legalization, the prevalence of moderately injured drivers with a THC level of at least 2 ng per milliliter in participating British Columbia trauma centers more than doubled. The increase was largest among older drivers and male drivers. (Funded by the Canadian Institutes of Health Research.).

Changes in California cannabis exposures following recreational legalization and the COVID-19 pandemic.

INTRODUCTION: Since 2012, eighteen states and the District of Columbia have legalized recreational cannabis. Past research suggests this policy change is associated with increased cannabis exposures however this has not yet been studied in California, despite its status as the world's largest legal cannabis market. METHODS: This observational, retrospective study analyzed trends in cannabis exposures reported to the California Poison Control System (CPCS) from 2010 to 2020. We assessed shifts in exposures before and after the legalization of recreational cannabis in November 2016, the establishment of recreational retail sales in January 2018, and the institution of a statewide shelter-in-place order due to the COVID-19 pandemic in March 2020 using interrupted time-series analysis and reviewed all records to identify specific products associated with exposures. RESULTS: Between 2010 and 2020 edible exposures increased from near zero to 79% of exposures in 2020. Cannabis exposures significantly increased following recreational legalization in 2016 (by an estimated 2.07 exposures per month [CI: 0.60, 3.55]; p < 0.01) and initiation of retail sales in 2018 (0.85 [CI: 0.12, 1.58]; p < 0.05). There was no significant change in cannabis exposures following the first shelter-in-place order of the COVID-19 pandemic (1.59 [CI: -1.61, 3.68]; p = 0.43). Cannabis exposures for those thirteen and under increased significantly both after recreational legalization (1.04 [CI: 0.38, 1.70]) and after the opening of the retail sales market (0.73 [CI: 0.34, 1.12]), but not following the shelter-in-place order (1.59 [CI: -1.61, 3.68]), nor was there a significant change for those older than thirteen. CONCLUSIONS: Our findings suggest that cannabis legalization is linked to increased exposures, particularly for products such as gummies and candy edibles among children under the age of thirteen. Clinicians should be aware of these risks and communicate them to patients, and policymakers should consider stronger regulations on packaging to reduce these exposures.Key pointsQuestion: How have cannabis exposures changed following legalization of recreational use, the opening of the recreational retail sales market, and the institution of shelter-in-place orders during the COVID-19 pandemic?Findings: In this retrospective review of 10,757 cases reported to the California Poison Control System (CPCS) between 2010 and 2020, exposures increased significantly after the legalization of recreational cannabis use and the opening of the recreational retail sales market, particularly among children, who primarily consumed candies and gummies.Meaning: Stronger regulation of cannabis edibles that mimic other products is warranted to decrease exposures among children.

When innovation outpaces regulations: The legal challenges for direct-to-patient supply of investigational medicinal products.

AIMS: We profile the lack of specific regulation for direct-to-patient postal supply (DTP) of clinical trial medications (investigational medicinal products, IMPs) calling for increased efficiency of patient-centred multi-country remote clinical trials. METHODS: Questionnaires emailed to 28 European Economic Area (EEA) Medical Product Licensing Authorities (MPLAs) and Swissmedic MPLA were analysed in 2019/2020. The questionnaire asked whether DTP of IMPs was legal, followed by comparative legal analysis profiling relevant national civil and criminal liability provisions in 30 European jurisdictions (including The Netherlands), finally summarising accessible COVID-19-related guidance in searches of 30 official MPLA websites in January 2021. RESULTS: Twenty MPLAs responded. Twelve consented to response publication in 2021. DTP was not widely authorised, though different phrases were used to explain this. Our legal review of national laws in 29 EEA jurisdictions and Switzerland did not identify any specific sanctions for DTP of IMPs; however, we identified potential national civil and criminal liability provisions. Switzerland provides legal clarity where DTP of IMPs is conditionally legal. MPLA webpage searches for COVID-19 guidance noted conditional acceptance by 19 MPLAs. CONCLUSIONS: Specific national legislation authorising DTP of IMPs, defining IMP categories, and conditions permitting the postage and delivery by courier in an EEA-wide clinical trial, would support innovative patient-centred research for multi-country remote clinical trials. Despite it appearing more acceptable to do this between EU Member States, provided each EU MPLA and ethics board authorises it, temporary Covid-19 restrictions in national Good Clinical Practice (GCP) guidance discourages innovative research into the safety and effectiveness of clinical trial medications.

The Legislative Approach and System Improvement of China's Compulsory Licensing for Drug Patents.

Compulsory licensing for drug patents is of great significance to ensure the accessibility of drugs. Although the development of China's compulsory licensing system for drug patents has been gradually improved, there are still problems. For example, the scope of the object is not realistic, the setting of the initiating subject is unreasonable, the reasons for issuance are not clear, the duration and scope of the license are not refined, and the provisions on the exploitation fee are missing. Consequently, in order to improve China's compulsory licensing system for drug patents, it is necessary to expand reasonably the scope of the object, remove the restrictions on the initiating subject, adjust the initiating rights of different subjects, determine the duration and scope of the license and the applicability of the hearing on a case-by-case basis, and determine a reasonable exploitation fee by taking into account the national income, patent cost, market share and other factors, in consideration of the flexibly international norms and the actual situation in China.

When technology precedes regulation: the challenges and opportunities of e-pharmacy in low-income and middle-income countries.

The recent growth of medicine sales online represents a major disruption to pharmacy markets, with COVID-19 encouraging this trend further. While e-pharmacy businesses were initially the preserve of high-income countries, in the past decade they have been growing rapidly in low-income and middle-income countries (LMICs). Public health concerns associated with e-pharmacy include the sale of prescription-only medicines without a prescription and the sale of substandard and falsified medicines. There are also non-health-related risks such as consumer fraud and lack of data privacy. However, e-pharmacy may also have the potential to improve access to medicines. Drawing on existing literature and a set of key informant interviews in Kenya, Nigeria and India, we examine the e-pharmacy regulatory systems in LMICs. None of the study countries had yet enacted a regulatory framework specific to e-pharmacy. Key regulatory challenges included the lack of consensus on regulatory models, lack of regulatory capacity, regulating sales across borders and risks of over-regulation. However, e-pharmacy also presents opportunities to enhance medicine regulation-through consolidation in the sector, and the traceability and transparency that online records offer. The regulatory process needs to be adapted to keep pace with this dynamic landscape and exploit these possibilities. This will require exploration of a range of innovative regulatory options, collaboration with larger, more compliant businesses, and engagement with global regulatory bodies. A key first step must be ensuring that national regulators are equipped with the necessary awareness and technical expertise to actively oversee this e-pharmacy activity.

Looking back from 2020, how cannabis use and related behaviours changed in Canada.

BACKGROUND: The Canadian government legalized non-medical cannabis use by adults in October 2018 to minimize associated harms and redirect profits from criminals. In October 2019, a wider array of products, including edibles, was legalized, with entry into the legal market beginning in December. DATA AND METHODS: Three quarters (the first quarters of 2018 and 2019 and the fourth quarter of 2020) of the National Cannabis Survey were used to examine changes in cannabis use (overall use and daily or almost daily (DAD) use), consumption methods, products and sources. RESULTS: Cannabis use in the past three months was higher in late 2020 (20.0%) than in 2019 (17.5%) and 2018 (14.0%), and this was particularly the case among: females (for whom rates rose to equal male rates for the first time), adults aged 25 and older, and some provinces. Similarly, DAD use, at 7.9% also increased. Higher percentages of Canadians reported getting at least some of their cannabis from legal sources or growing it, and fewer were relying on friends and family or illegal sources in 2020. DISCUSSION: This study spans three years-from before legalization to about two years after. It provides a more complete picture of the law's impact on cannabis use and related behaviours, given the more established legal cannabis industry better equipped to compete with the black market on price, convenience and selection. Findings demonstrate that change is continuing, and, as before, some cautions and assurances remain. The impact of the COVID-19 pandemic on cannabis use continues to be difficult to measure. Monitoring remains important, given the ever-changing provincial retail landscapes; the introduction of new products; and the pressure by the industry to remove or adjust potency limits, and allow widespread delivery, farm-gate sales and cannabis lounges.