Association between legalization of recreational cannabis and fatal motor vehicle collisions in the United States: an ecologic study.

BACKGROUND: With the recent legalization of recreational cannabis in Canada, cannabis-impaired driving is an important public safety concern. Our aim was to examine the association between recreational cannabis legalization and fatal motor vehicle collisions using data from the United States, which present a timely natural experiment of cannabis legalization. METHODS: We conducted an ecologic study using the number of fatal motor vehicle collisions and the associated number of deaths for US jurisdictions with legalized recreational cannabis (2007-2018) retrieved from the US Fatality Analysis Reporting System. We examined jurisdiction-specific rates of fatal motor vehicle collisions and associated deaths before and after recreational cannabis legalization using Poisson regression and meta-analyzed estimates across jurisdictions using DerSimonian and Laird random-effects models. RESULTS: After adjustment for calendar year, legalization was associated with increases in rates of fatal motor vehicle collisions (incidence rate ratio [IRR] 1.15, 95% confidence interval [CI] 1.06-1.26) and associated deaths (IRR 1.16, 95% CI 1.06-1.27). Differences between the first 12 months after legalization relative to subsequent months were inconclusive for rates of fatal motor vehicle collisions (IRR 0.92, 95% CI 0.84-1.02) and associated deaths (IRR 0.92, 95% CI 0.84-1.01). INTERPRETATION: Recreational cannabis legalization in the US was associated with a relative increased risk of fatal motor vehicle collisions of 15% and a relative increase in associated deaths of 16%, with no conclusive difference between the first and subsequent years after legalization. These findings raise concern that there could be a similar increase in fatal motor vehicle collisions and associated deaths in Canada following recreational cannabis legalization.

Cannabis use, use frequency, and use disorder in large metropolitan, small metropolitan, and nonmetropolitan areas.

BACKGROUND: Despite significant geographical heterogeneity of sociodemographic and clinical characteristics, little is known about potential differences in cannabis use behaviors in U.S. geographic areas. In this study, we examined cannabis use behaviors in large metropolitan, small metropolitan, and nonmetropolitan areas. We focused on interactions between geographic areas and health insurance status and medical cannabis laws (MCL). METHODS: Data came from the 2015-2018 National Survey on Drug Use and Health (NSDUH; N = 171,766 adults; N = 36,175 cannabis users). Weighted chi-squares tests of independence and multivariable Poisson regression models were used to examine study questions. RESULTS: Past-year use was highest in large metropolitan areas (16.08 %). Frequent use was highest among nonmetropolitan area users (48.67 %). Uninsured adults had a higher likelihood of past-year use (RRR = 1.21, 95 % CI = 1.14, 1.29) and frequent use (RRR = 1.27, 95 % CI = 1.14, 1.41), but a lower likelihood of cannabis use disorder (RRR = 0.77, 95 % CI = 0.66, 0.89). Uninsured adults in nonmetropolitan areas had a higher likelihood (RRR = 1.62, 95 % CI = 1.39, 1.88) of past-year use than insured nonmetropolitan area adults. MCL state residency was associated with a higher likelihood of frequent use among nonmetropolitan (RRR = 1.39, 95 % CI = 1.11, 1.74) and small metropolitan users (RRR = 1.30, 95 % CI = 1.15, 1.47). Cannabis use disorder likelihood did not vary by geographic area. CONCLUSIONS: Lack of health insurance and MCL state residency are significant variables affecting cannabis use behaviors in small metropolitan and/or nonmetropolitan areas.

Initial development of a brief assessment of cocaine demand.

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand.

Impact of changes in controlled drugs legislation on benzodiazepine receptor agonist prescribing in Ireland: a repeated cross-sectional study.

PURPOSE: To examine the impact of new controlled drugs legislation introduced in May 2017 on benzodiazepine receptor agonist (BZRA) prescribing in Ireland. METHODS: A repeated cross-sectional analysis was conducted using publically available monthly pharmacy claims data from the General Medical Services (GMS) database. The study population comprised all GMS-eligible individuals aged ≥ 16 years from January 2016 to September 2019. Monthly prevalence rates of individuals receiving BZRA prescriptions per 10,000 eligible population were calculated and trends examined over time. Segmented linear regression of prevalence rates was used to examine changes before and after introduction of the legislation stratified by gender and age groups. Regression coefficients (ß) and 95% confidence intervals (CIs) for monthly change were calculated. RESULTS: Pre-legislation (January 2016 to April 2017), there was a significant monthly decline in benzodiazepine prevalence rate (ß = - 1.18; 95% CI - 1.84, - 0.51; p < 0.001) but no significant change in Z-drug prescribing. Post-legislation (May 2017 to September 2019), increases in prevalence rates were observed for benzodiazepines (ß = 1.04; 95% CI 0.17, 1.92; p = 0.021) and Z-drugs (ß = 1.04; 95% CI 0.26, 1.83; p = 0.010). Post-legislation trends showed increases in BZRA prevalence rates among the youngest subgroup (16-44 years), with variable changes in the middle-aged subgroup (45-64 years) and no changes in the oldest subgroup (≥ 65 years). CONCLUSIONS: This study indicates that introduction of new legislation had limited impact on BZRA prescribing on the main public health scheme in Ireland. Interventions targeting specific population subgroups may be required to achieve sustained reductions in prescribing.

Chemical and statistical analyses of blotter paper matrix drugs seized in the State of Rio de Janeiro.

Drugs of abuse are psychoactive substances illicitly distributed and used worldwide. In Rio de Janeiro, Brazil, they represent a public health issue and are directly related to several social problems. The recent increase in appearances of new psychoactive substances (NPS), derived from structural modifications of existing psychoactive substances, poses a threat to public health and forensic laboratories worldwide, as little is known about these substances. This study aimed to chemically and geographically map drugs of abuse from blotter papers seized by the Civil Police of Rio de Janeiro State (PCERJ) between 2006 and 2019. High-performance analytical techniques, such as gas chromatography-mass spectrometry (GC-MS) and Orbitrap mass spectrometry (Orbitrap-MS), combined with statistical analyses, were employed to characterize the seized samples. The most common chemical compounds in NPS found in this study were synthetic phenethylamines, i.e., molecules from the 25I-NBOH (2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol) and 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) families. Prior to 2014, the majority of seized blotter papers contained lysergic acid diethylamide (LSD) and were concentrated in the Metropolitan region. An upsurge in blotter paper seizures was observed from 2014 to 2017; the most common substances during this time were from the NBOMe family. NBOH compounds emerged in 2016 in coastal regions with high tourism, reaching over 1300 items only in 2017. Only one synthetic cannabinoid was found among the blotter papers seized in Rio de Janeiro between 2006 and 2019. The assembled chemical data and statistical analyses allowed the mapping and monitoring of the chemical profiles of the seized blotter papers, providing a strong foundation for the understanding of the origins and movement of these drugs around the RJ State.

Association of Electronic Prescribing of Controlled Substances With Opioid Prescribing Rates.

Importance: The majority of US states have passed mandates requiring the use of electronic prescribing of controlled substances (EPCS) as a tool to reduce rates of opioid prescribing. It is not known whether increasing use of EPCS will have the intended effect. Objective: To assess the association between use of EPCS and trends in opioid prescribing. Design, Setting, and Participants: In this retrospective, longitudinal cohort study of all patients and prescribers in the 50 US states and the District of Columbia from 2010 to 2018, changes in state-level use of EPCS and concurrent changes in opioid prescribing in each state are described. Then the association between changes in the use of EPCS and opioid prescribing are estimated using state and year fixed-effects models that include covariates for policy change and state demographic change. Data Analysis was performed on May 5, 2020. Main Outcomes and Measures: The proportion of controlled substances in each state prescribed using EPCS based on opioid prescriptions per 100 persons and morphine milligram equivalents (MME) of opioids. Results: In 2018, the population-weighted percent of opioids prescribed using EPCS was 27%, up from 0% as of 2013. National rates of opioid prescriptions decreased from 78 prescriptions per 100 persons in 2013 to 53 in 2018. Over the same period, there was a decrease from 64 071 MME per 100 persons in 2013 to 40 906 MME per 100 persons in 2018, representing 36% of the 2013 level. By 2018, EPCS increased to 69.4% in states with mandates for its use and 23.6% in states without mandates. In multivariable models, a 10 percentage-point increase in the use of EPCS was associated with an additional 2 prescriptions per 100 persons (95% CI, 1.3-2.8) and a 0.8% (95% CI, 0.06%-1.5%) increase in MME per 100 persons. Conclusions and Relevance: These data suggest that an increased use of EPCS was not associated with decreased opioid prescribing or a decrease in the amount prescribed and may have been associated with a small increase in opioid prescribing. Opioid prescribing is associated with a variety of social and public health factors, and thus, despite the appeal, EPCS adoption alone may be insufficient to reduce opioid prescribing. Policy makers should consider levers to ensure that EPCS is integrated with outside data and that information is actively used to inform prescribing decisions.

Community Pharmacies in Poland-The Journey from a Deregulated to a Strictly Regulated Market.

Community pharmacies are the primary entities providing drugs to individual patients in Poland. The pharmacy market has been changing for many years due to significant changes in market regulations. These changes significantly affect the profitability of pharmacies, which may impact the quality of pharmacotherapy. The small number of pharmacies, which resulted from changes in the law in 2017, can influence the level of patient care. The article presents the community pharmacies market in Poland. Particular attention is paid to the legal regulations affecting community pharmacies and the impact of these regulations on the overall shape of the market. The Polish system's specificity, including the pharmacy market indicators, has been compared with data from other European Union countries.

State-level marijuana policies and marijuana use and marijuana use disorder among a nationally representative sample of adults in the United States, 2015-2017: Sexual identity and gender matter.

BACKGROUND: Research demonstrates an association between state-level medical marijuana laws (MMLs) and increased marijuana use (MU) and MU disorder (MUD) among adults, but has yet to explore this association among lesbian, gay and bisexual (LGB) individuals, including gender differences. METHODS: We pooled the 2015-2017 National Survey on Drug Use and Health data for adults (n = 126,463) and used gender-stratified adjusted multivariable logistic regression to model the odds of past-year MU, past-year medical MU, daily/near-daily MU, and MUD; we also tested the interaction between MML state residence and sexual identity. RESULTS: Bisexual women had higher past-year MU (40% versus 10.3%; aOR = 2.9[2.4-3.4]), daily/near-daily MU (9.8% versus 1.5%; aOR = 4.6[3.3-6.2]), and medical MU ((5.5% versus 1.2%) aOR = 5.5[3.8-8.1]) than heterosexual women. Gay/lesbian women also had higher past-year MU (26.1% versus 10.3%; aOR = 2.8[2.2-3.7]), daily/near-daily MU (5.6% versus 1.5%; aOR = 2.9[1.8-4.6]), and medical MU (4.7% versus 1.2%; aOR = 3.0(1.4-6.6]) than heterosexual women. Bisexual women in MML states had higher past-year MU ((44.4% vs. 34.1%); aOR = 1.8[1.5-2.1]) and medical use (7.1% vs. 3.3% (aOR = 2.5[1.5-3.9]) than bisexual women in non-MML states. The odds of any past-year medical MU for bisexual versus heterosexual women was different in MML versus non-MML states (Exponentiated ß = 0.53, p = 0.01). Gay men in MML states had higher past year MU (31.2% versus 25.7%; aOR = 1.6[1.1-2.5] and medical MU (6.4% vs 1.7%; aOR = 5.0[4.2-6.1]) than gay men in non-MML states. CONCLUSIONS: Results suggest that MMLs may differentially impact MU for sexual minority individuals-particularly bisexual women. Findings demonstrate the need for states enacting MMLs to consider potential differential impacts on LGB populations.

Impact of Schedule IV controlled substance classification on carisoprodol utilization in the United States: An interrupted time series analysis.

BACKGROUND: In January 2012, the Drug Enforcement Agency (DEA) classified carisoprodol as a Schedule IV controlled substance at the US federal level. We aimed to examine the effect of this policy on the use of carisoprodol in a commercially-insured population. METHODS: This interrupted time series study included individuals with musculoskeletal disorders in the IBM MarketScan Commercial Database between December 2009 and February 2014. We used comparative segmented linear regression to assess changes in the proportions of patients who filled/newly filled carisoprodol each month. RESULTS: A total of 13.3 million patients were included. 29 states with no scheduling prior to the DEA classification had lower baseline prevalence of carisoprodol use compared to 17 states that had scheduled carisoprodol individually before 2010 (11.0 vs. 21.1 patients with fills per 1000 patients). The federal scheduling was associated with an immediate decline (-1.12 per 1000 patients, p < 0.01) and decreasing trend in prevalence (-0.07 per 1000 patients per month, p = 0.02). This effect was not modified by existing state-level scheduling status. During the first, second, third, and fourth 6-month periods after federal scheduling, the relative difference between observed and predicted prevalence was 7.8%, 10.5%, 13.4%, and 19.8%. Similar patterns were observed for carisoprodol initiation. Overall, declining use was more pronounced among younger age groups and patients with injury. CONCLUSIONS: Schedule IV controlled substance classification at the federal level was associated with a moderate reduction in the dispensing of carisoprodol regardless of whether scheduling was already present at the state level.

Lower smoking rates and increased perceived harm of cigarettes among French adults one year after comprehensive tobacco control measures.

CONTEXT: France has high smoking rates, and recently intensified tobacco control policies spearheaded by the introduction of plain tobacco packaging (PP), and an increase in graphic health warnings (GHW). We examine smoking and e-cigarettes use rates, as well as smoking-related perceptions before (2016) and one year after (2017) comprehensive tobacco control measures. METHODS: DePICT is a two waves cross-sectional national telephone survey of French adults aged 18-64 years (2016: 4456 - 2017: 4114). Data were weighted to be representative of the French adult population. Adjusted prevalence ratios (PR, 95% CI) estimating changes between the two study waves were calculated using multivariate Log-Binomial regression models. MAIN FINDINGS: In 2017, as compared with 2016, smoking rates (PR = 0.93 (0.88-0.99) and current e-cigarette use (PR = 0.76 (0.61-0.96)) decreased in France. Further, French adults were more likely to report fear of the consequences of smoking (PR = 1.10 (1.06-1.14)) and that smoking is dangerous (PR = 1.08 (1.06-1.11)). Smokers were also more likely to report that health messages on tobacco products are efficient (PR = 1.18 (1.05-1.32)). CONCLUSIONS: Our study provides early and encouraging results on potential effects of the comprehensive tobacco control strategies in France introduced in 2017, including PP and larger GHW. Our findings also suggest that e-cigarettes did not replace traditional smoking.

Are risk minimization measures for approved drugs in Europe effective? A systematic review.

Objectives: The effectiveness of risk minimization measures (RMMs) requires evaluation. This study aims to evaluate the results of cross-sectional surveys assessing the effectiveness of RMMs in Europe (EU RM Surveys) and review the regulatory consequences. Methods: The authors searched for study reports and manuscripts of completed EU RM surveys in the EU PAS Register, MEDLINE, and Google between 01/2011 and 01/2018. Regulatory responses were extracted from Assessment Reports. Random effects models to combine proportions were used. Results: Twenty-four EU RM surveys were identified. Twenty-three studies targeted health-care professionals (HCPs). The pre-specified sample size was reached in 52% of studies. HCP participation was 5% defined as completers/invited and 89% for completers/eligible. Receipt of materials was recalled by 60% of HCPs and 77% of items scored knowledge >60%. Eight studies targeted patients/caregivers. The pre-specified sample size was reached in only two. Participation was 93%, defined as completers/eligible. Materials were received by 50-80% of patients and read by over 90%. Patients only scored knowledge >60% in 38% of items. Further action was requested by regulators in 59% of studies. Conclusion: Surveys are necessary to evaluate many RMMs. Challenges remain in the design, conduct, and reporting of these studies which may benefit from the use of standard definitions and further guidance on reporting. EU PAS Register: http://www.encepp.eu/encepp/viewResource.htm?id=23435.

Trajectories of dispensed prescription opioids among beneficiaries enrolled in a Medicaid controlled substance "lock-in" program.

PURPOSE: "Lock-in" programs (LIPs) are used by health insurers to address potential substance (eg, opioid) misuse among beneficiaries. We sought to (1) examine heterogeneity in trajectories of dispensed opioids (in average daily morphine milligram equivalents (MMEs)) over time: prior to, during, and following release from a LIP, and (2) assess associations between trajectory patterns and beneficiary characteristics. METHODS: Medicaid claims were linked to Prescription Drug Monitoring Program records for a cohort of beneficiaries enrolled in the North Carolina Medicaid LIP (n = 2701). Using latent class growth analyses, we estimated trajectories of average daily MMEs of opioids dispensed to beneficiaries across specific time periods of interest. RESULTS: Five trajectory patterns appeared to sufficiently describe underlying heterogeneity. Starting values and slopes varied across the 5 trajectory groups, which followed these overall patterns: (1) start at a high level of MMEs, end at a high level of MMEs (13.1% of cohort); (2) start medium, end medium (13.2%); (3) start medium, end low (21.5%); (4) start low, end medium (22.6%); and (5) start low, end low (29.6%). We observed strong associations between patterns and beneficiaries' demographics, substance use-related characteristics, comorbid conditions, and healthcare utilization. CONCLUSIONS: In its current form, the Medicaid LIP appeared to have limited impact on beneficiaries' opioid trajectories. However, strong associations between trajectory patterns and beneficiary characteristics provide insight into potential LIP design modifications that might improve program impact (eg, LIP integration of substance use disorder assessment and referral to treatment, assessment and support for alternate pain therapies).

Cannabis Prevalence and National Drug Policy in 27 Countries: An Analysis of Adolescent Substance Use.

Prior research that assesses the relationship between cannabis policy and prevalence rates has yielded mixed results, perhaps due to the varying rigor of these investigations. Addressing some of these issues in rigor and informed by a rational choice theory (RCT), we hypothesize that those policies on the more punitive end of McDonald and colleagues' classification will be most effective. Examining legislation in 27 countries utilizing the Second International Self-Report Delinquency Study (ISRD-2) through hierarchical linear modeling (HLM) models with both individual- and country-level controls, we find little support for these hypotheses. Instead, results from our analysis largely indicate that the variation in country prevalence rates from 2005 to 2007 was not significantly related to cannabis control policy. We comment on possible policy implications for these preliminary results.

When DAWN went dark: Can the Nationwide Emergency Department Sample (NEDS) fill the surveillance gap left by the discontinued Drug Abuse Warning Network (DAWN)?

BACKGROUND: This study assessed whether the Nationwide Emergency Department Sample (NEDS) could reliably fill the national drug surveillance gap caused by the discontinuation of the Drug Abuse Warning Network (DAWN). METHODS: Estimates of the drug-related emergency department (ED) visits derived from DAWN (2004-2011) and NEDS (2006-2013). Estimates of the underlying reason for the drug-related ED visit, patient characteristics, and the specific drugs involved were compared for 2011, the most recent overlapping data year in DAWN and NEDS. Trends in ED visits for major drugs of abuse were then compared over the period 2004-2013. RESULTS: In 2011, DAWN and NEDS produced statistically similar estimates of the overall number of drug-related ED visits (5.1 vs. 4.9 million) and those involving drug misuse or abuse (2.65 vs. 2.77 million). Among the latter, estimates by gender, age group, and patient disposition were generally consistent across data systems, suggesting that NEDS and DAWN samples draw from a similar population. Main analyses reveal statistically similar estimates across data systems in both levels and trends for cocaine, amphetamines, and narcotic pain relievers. In contrast, the number of ED visits for sedatives and heroin was significantly undercounted in NEDS, whereas marijuana-related ED visits were undercounted in DAWN. CONCLUSIONS: This study demonstrates the utility of NEDS for conducting post-DAWN drug surveillance. Because NEDS cannot provide targeted surveillance of certain established (e.g., heroin) and emerging (e.g., fentanyl) drugs, however, it is critical that a data system that employs medical record-based reviews be implemented to augment the known weaknesses of NEDS.

Determination of Similarity Margin in Comparative Clinical Studies to Support the Development of Biosimilar Products of Neupogen® (Filgrastim, Granulocyte Colony-Stimulating Factor [G-CSF]).

To demonstrate a biological product is biosimilar to a reference product, the applicant needs to show that the product is highly similar and has no clinically meaningful differences. Comparative clinical studies are often conducted to support the conclusion of no clinically meaningful differences, as a part of totality of evidence. The FDA has published several guidance documents to facilitate the development of biosimilar products. While the guidance documents define the role and objective of comparative clinical studies, they do not provide details about the determination of the similarity margin. In this paper, we illustrate a similarity margin derivation for a surrogate endpoint in comparative clinical studies conducted to assess whether clinically meaningful differences exist between Neupogen® (Filgrastim, granulocyte colony-stimulating factor) and products proposed to be biosimilar to Neupogen®.