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Controls on essential/precursor chemicals from commercial companies have been associated with many large downturns in illicit drug markets and attendant problems. My colleagues and I brought this to light in the studies that are the subject of Giommoni's review. McKetin et al. in an earlier review considered several of our studies on chemical controls for methamphetamine, all centered in North America. Giommoni discusses not only those studies but also our later work on chemical controls for cocaine and heroin. This later work evaluates US essential/precursor chemical policies targeting illicit drug producers outside of North America, and it examines impacts on illicit drug availability and use (the studies reviewed by McKetin et al. predominantly focused on outcomes such as drug-related hospitalizations, arrests, and treatment). Giommoni's review is a new resource that will help make the varied topics in essential/precursor chemical control research more accessible to many readers. After noting this, I discuss some common methodological misconceptions about our studies. For example, our studies generally used multi-replication interrupted time series analysis, a research design among the most powerful of all quasi-experimental designs. Authors, however, typically discuss the studies as if they used single-intervention interrupted time series analysis, a less powerful design. Multi-replication and single-intervention interrupted time series analyses also differ regarding likely confounders; awareness of this is critical to accurately assessing our findings and critiquing alternative explanations. Finally, I note that commercial chemical companies function as the silent, albeit usually unwitting, partners in the large-scale production of several illicit drugs, including fentanyl. And many governments are implementing essential/precursor chemical controls to help stymie this partnership. But they are doing so largely without evaluation and study-a poor policy practice. To remedy this, I suggest establishing multi-disciplinary applied research teams to help assess, guide and improve essential/precursor chemical control efforts., Competing Interests: Declaration of competing interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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 (β) 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 (β = - 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 (β = 1.04; 95% CI 0.17, 1.92; p = 0.021) and Z-drugs (β = 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.

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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© 2021 Joule Inc. or its licensors.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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 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.

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 β = 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier B.V.)

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.

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.

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)., (© 2018 John Wiley & Sons, Ltd.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study uses data from the Fatality Analysis Reporting System and a differences-in-differences model to examine the effect of state medical marijuana laws (MMLs) on cannabis-involved driving among U.S. drivers involved in a fatal crash between 1993-2014. Findings indicate that MMLs in general have a null effect on cannabis-positive driving, as do state laws with specific supply provisions including home cultivation and unlicensed or quasi-legal dispensaries. Only in jurisdictions with state-licensed medical marijuana dispensaries did the odds of marijuana-involved driving increase significantly by 14 percent, translating into an additional 87 to 113 drivers testing positive for marijuana per year. Sensitivity analyses reveal these findings to be generally robust to alternate specifications, although an observed spillover effect consistent with elevated drugged driving enforcement in bordering states weakens a causal interpretation. Still, reasonable policy implications are drawn regarding drugged driving prevention/enforcement and regulations governing dispensary delivery services and business siting decisions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 ® .

Background: In 2011-2013, >95% of the global opioid analgesics consumption occurred in three regions, accounting for 15% of the world population. Despite abundant literature on barriers to access, little is known on the correlation between actual access to opioid analgesics and barriers to access, including legal and regulatory barriers., Objective: This study aimed to evaluate the correlation between access to strong opioid analgesics and barriers to access in national legislation and regulations in 11 central and eastern European countries that participated in the Access to Opioid Medication in Europe (ATOME) project., Design: Two variables were contrasted to assess their correlation: the country level of access to strong opioid analgesics indicated by the Adequacy of Consumption Measure (ACM) and the number of potential legal and regulatory barriers identified by an external review of legislation and regulations., Measurements: A linear correlation was evaluated using a squared linear correlation coefficient., Results: Evaluation of the correlation between the ACM and the number of potential barriers produces an R 2 value of 0.023 and a correlation plot trend line gradient of -0.075, indicating no correlation between access to strong opioid analgesics and the number of potential barriers in national legislation and regulations in the countries studied., Conclusions: No correlation was found, which indicates that other factors besides potential legal and regulatory barriers play a critical role in withholding prescribers and patients essential pain medication in the studied countries. More research is needed toward better understanding of the complex interplay of factors that determine access to strong opioid analgesics.

Objective: The authors sought to determine whether cannabis use is associated with a change in the risk of incident nonmedical prescription opioid use and opioid use disorder at 3-year follow-up., Method: The authors used logistic regression models to assess prospective associations between cannabis use at wave 1 (2001-2002) and nonmedical prescription opioid use and prescription opioid use disorder at wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Corresponding analyses were performed among adults with moderate or more severe pain and with nonmedical opioid use at wave 1. Cannabis and prescription opioid use were measured with a structured interview (the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version). Other covariates included age, sex, race/ethnicity, anxiety or mood disorders, family history of drug, alcohol, and behavioral problems, and, in opioid use disorder analyses, nonmedical opioid use., Results: In logistic regression models, cannabis use at wave 1 was associated with increased incident nonmedical prescription opioid use (odds ratio=5.78, 95% CI=4.23-7.90) and opioid use disorder (odds ratio=7.76, 95% CI=4.95-12.16) at wave 2. These associations remained significant after adjustment for background characteristics (nonmedical opioid use: adjusted odds ratio=2.62, 95% CI=1.86-3.69; opioid use disorder: adjusted odds ratio=2.18, 95% CI=1.14-4.14). Among adults with pain at wave 1, cannabis use was also associated with increased incident nonmedical opioid use (adjusted odds ratio=2.99, 95% CI=1.63-5.47) at wave 2; it was also associated with increased incident prescription opioid use disorder, although the association fell short of significance (adjusted odds ratio=2.14, 95% CI=0.95-4.83). Among adults with nonmedical opioid use at wave 1, cannabis use was also associated with an increase in nonmedical opioid use (adjusted odds ratio=3.13, 95% CI=1.19-8.23)., Conclusions: Cannabis use appears to increase rather than decrease the risk of developing nonmedical prescription opioid use and opioid use disorder.

Background: The War on Drugs has raised the incarceration rates of racial minorities for non-violent drug-related crimes, profoundly stigmatized drug users, and redirected resources from drug prevention and treatment to militarizing federal and local law enforcement. Yet, while some states consider shifting their punitive approach to drug use, to one based on drug treatment and rehabilitation, nothing suggests that these policy shifts are being replicated in Puerto Rico., Methods: This paper utilizes data from 360 PWID residing in four rural towns in the mountainous area of central Puerto Rico. We initially recruited 315 PWID using respondent-driven sampling (RDS) and collected data about risk practices and conducted HIV and HCV testing. During a second phase, we conducted 34 micro-ethnographic assays, in which we randomly recruited 34 participants from the first phase and included their ego networks in this phase. Our ethnographic inquiry produced significant data regarding the effects of the war on drugs on the local drug trade, drug availability, and injectors' social networks., Results: Findings suggest that repressive policing has been ineffective in preventing drug distribution and use among those in our study. This type of law enforcement approach has resulted in the disproportionate incarceration of poor drug users in rural Puerto Rico, and mainly for nonviolent drug-related crimes. In addition, incarceration exposes PWID to a form of a cruel and unusual punishment: having to quit heroin "cold turkey" while the prison environment also represents a HIV/HCV risk. In turn, the war on drugs not only diverts resources from treatment but also shapes treatment ideologies, punishing non-compliant patients., Conclusion: Shifting the emphasis from repression to treatment and rehabilitation is likely to have a positive impact on the health and overall quality of life of PWID and their communities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: A widespread sense of a failing criminal justice system and increased feelings of insecurity changed the response to crime into a culture of control, which is characterized by policies that punish and exclude. In the Netherlands, these influences can be witnessed in the war on drugs where local authorities use their administrative power to close homes involved in drug-related crime. Citizens can invoke judicial review over these administrative interferences by claiming that such closure results in an unfair balance between purposes, means and consequences. This paper assesses whether judicial review functions as a safety net against losing one's home due to drug-related crime., Methods: We used doctrinal legal research methods to examine the "law in the books" and empirical legal research methods to analyse the "law in action". We used a survey to investigate how often the drug-related closure power was used in 2015, and we statistically analysed all published case law of Dutch lower courts between 2007 and 2016., Results: The scope of the closure power broadened over the years and our data show that local authorities fiercely make use of this instrument. In 41.4% of the cases, citizens are successful in fighting the closure. While scholarly literature indicates that judicial courts function as safeguards by questioning the proportionality of administrative action, raising a proportionality defence does not necessarily result in a more favourable outcome for citizens. In fact, raising a proportionality defence makes it more likely to result in dismissal of the appeal., Conclusion: The stretched scope of the drug-related closure power together with the relatively low success rate of citizens who fight the loss of their home and a seemingly meaningless proportionality check show no sign of a safety net against the loss of one's home at the suit of a local authority., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

In Japan, a pharmacy or drug store license is required for selling pharmaceutical products. However, civilians without a pharmacy or drug store license are displaying pharmaceutical products for sale on a flea market application, which is illegal dealing. This study discussed the modality for implementing countermeasures for the illicit selling of pharmaceutical products. We extracted pharmaceutical products displayed for sale on three flea market applications (Mercari, Rakuma, Fril) on one day. One hundred and eighty-one pharmaceutical products were displayed (49 on Mercari, 86 on Rakuma, and 46 on Fril). There were 6.1% (11/181) domestically prescribed drugs, 69.1% (125/181) domestic OTC drugs, 23.8% (43/181) foreign-made prescribed drugs, and 1.1% (2/181) foreign-made OTC drugs. The seller could display the product for sale without confirming whether it is prohibited. We alerted the service providers of this illicit selling at flea markets at three different instances. The pharmaceutical product displays were deleted by the service providers at a rate of 55.1% (27/49) for Mercari and 51.2% (44/86) for Rakuma. The average number of drugs that were displayed for sale by each seller was 1.4 and the average number of total products that were displayed for sale by each seller was 100. The seller could have unintentionally displayed the pharmaceutical products for sale, without the knowledge that it is illegal. The service providers of flea market applications should create mechanisms to alert the sellers that displaying pharmaceutical products for sale is an illicit act and regulate these violations.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare that we have no competing interests. Provenance and peer review: Commissioned; externally peer reviewed.

When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The proliferation of new psychoactive substances (NPS) has been a global trend in drug abuse and its regulation has been a worldwide concern. There is no doubt that it is necessary to share information related to these emerging substances between countries and continents for the effective regulation of NPS. With efforts for the efficient regulation of NPS, many studies and information have been published for the prevalence of NPS in the United States and other countries in Europe and Oceania. However, there is lack of information available for the prevalence of NPS in Asian and African countries. Therefore, this research was focused on the investigation of legal status of certain NPS in Northeast Asian countries, including China, Japan, South Korea and Taiwan, in order to provide information on the prevalence and trend of emerging NPS in these countries. The results showed that a total of 940 NPS was reported in 4 Northeast Asian countries from 2007 to 2015. Among 940 NPS, 882 NPS are legally restricted in at least one country (94%) and 96 substances were not currently under control (6%) in these countries. The number of controlled NPS that are currently controlled in all 4 countries was only 25 (or 28%) out of 882 NPS. Each substance was categorized in 9 groups according to the classification proposed by the United Nations Office on Drugs and Crime (UNODC). In Northeast Asia, the most commonly controlled NPS were synthetic cannabinoids, synthetic cathinones, and phenethylamines. It was found that Japan is the most proactive country in terms of the NPS regulation with 41% of the total number of controlled NPS in Northeast Asia, followed by South Korea (21%), China (28%), Taiwan (10%). Comparing the number of NPS newly regulated in each country every year, NPS has been broadly scheduled in 2011 and the number of scheduled NPS has dramatically increased from 2013 to 2015. It was shown that Northeast Asia is also in danger of these emerging NPS and the effective regulation across countries is important for the prevention of NPS. Also, this study will bring attention to local law enforcement in the construction of local drug crime prevention network sharing information for these controlled substances., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: To assess the associations between types of cannabis control policies at country level and prevalence of adolescent cannabis use., Setting, Participants and Design: Multilevel logistic regressions were performed on 172,894 adolescents 15 year of age who participated in the 2001/2002, 2005/2006, or 2009/2010 cross-sectional Health Behaviour in School-Aged Children (HBSC) survey in 38 European and North American countries., Measures: Self-reported cannabis use status was classified into ever use in life time, use in past year, and regular use. Country-level cannabis control policies were categorized into a dichotomous measure (whether or not liberalized) as well as 4 detailed types (full prohibition, depenalization, decriminalization, and partial prohibition). Control variables included individual-level sociodemographic characteristics and country-level economic characteristics., Findings: Considerable intra-class correlations (.15-.19) were found at country level. With respect to the dichotomized cannabis control policy, adolescents were more likely to ever use cannabis (odds ratio (OR) = 1.10, p = .001), use in past year (OR = 1.09, p = .007), and use regularly (OR = 1.26, p = .004). Although boys were substantially more likely to use cannabis, the correlation between cannabis liberalization and cannabis use was smaller in boys than in girls. With respect to detailed types of policies, depenalization was associated with higher odds of past-year use (OR = 1.14, p = .013) and regular use (OR = 1.23, p = .038), and partial prohibition was associated with higher odds of regular use (OR = 2.39, p = .016). The correlation between cannabis liberalization and regular use was only significant after the policy had been introduced for more than 5 years., Conclusions: Cannabis liberalization with depenalization and partial prohibition policies was associated with higher levels of regular cannabis use among adolescents. The correlations were heterogeneous between genders and between short- and long-terms.

Objective: To determine the association between prescription drug monitoring program (PDMP) implementation and emergency department (ED) visits involving opioid analgesics., Methods: Rates of ED visits involving opioid analgesics per 100,000 residents were estimated from the Drug Abuse Warning Network dataset for 11 geographically diverse metropolitan areas in the United States on a quarterly basis from 2004 to 2011. Generalized estimating equations assessed whether implementation of a prescriber-accessible PDMP was associated with a difference in ED visits involving opioid analgesics. Models were adjusted for calendar quarter, metropolitan area, metropolitan area-specific linear time trends, and unemployment rate., Results: Rates of ED visits involving opioid analgesics increased in all metropolitan areas. PDMP implementation was not associated with a difference in ED visits involving opioid analgesics (mean difference of 0.8 visits [95% CI: -3.7 to 5.2] per 100,000 residents per quarter)., Conclusions: During 2004-2011, PDMP implementation was not associated with a change in opioid-related morbidity, as measured by emergency department visits involving opioid analgesics. Urgent investigation is needed to determine the optimal PDMP structure and capabilities to improve opioid analgesic safety., (Published by Elsevier Ireland Ltd.)

IInter-state movement of drugs between EU countries by pharmaceutical companies and distribution warehouses is a permitted activity called parallel trade. As Spain is among the states with lower price of these products, its main activity is shipping to other countries; however, a phenomenon has emerged in acquiring drugs for this purpose, called "reverse traffic" that develops without observing the health regulations in the legal distribution channel in our country; in which, the pharmaceutical distribution warehouses, rather than getting drugs from other pharmaceutical companies or pharmaceutical distribution warehouses under the current legislation, obtain them from community pharmacies, thus reversing the legal supply circuit, as this drugs do not end dispensed to the public. This paper studies the risks to public health caused by these practices, detailing the results of health inspections in Galicia, where in relation to the total pharmaceutical establishments sanctioning procedures in the period 2011-2014, were sanctioned for this reason 15 community pharmacies and 5 distribution warehouses, the maximum fines belonging to a network consisting of a pharmaceutical distribution warehouse, with a 1,000,000 € fine and closure for 3 years, and 4 community pharmacies, with 2,400,000 € total fine; It also specifies the methodology of action, identifies the scene of illegal acquisition to make this trade with the greatest economic benefits, highlights the strengths of the success and further action to improve its approach.

Introduction: Disproportionality analysis (DA) of adverse drug reactions spontaneous reporting (SR) databases is used to identify signals of disproportionate reporting (SDR). The objective of this study was to identify the generation of SDR in the published literature and whether it led to regulatory action., Methods: A systematic literature search in MEDLINE and Cochrane Central Register for Controlled Trials (CENTRAL) in a 10-year period, from 2005 to 2014, was conducted, to identify studies designed to detect drug safety signals through the use of disproportionality measures applied to spontaneous reporting databases of adverse drug reactions., Results: Seventy three studies were included. The number of publications has been rising over the study time period. Forty nine studies focus on drug-event combinations. Large international and smaller national or regional databases were identified. The disproportionality measures applied included frequentist and Bayesian methods and some studies used more than one method. SDRs were identified in more than ninety percent of the studies. Ten studies were found to be confirmatory of previous regulatory decision., Conclusion: It was not found any safety signal issued by drug regulatory agencies exclusively generated by DA. More research devoted to this issue is needed, since the value of these methods on drug safety signaling and their impact on drug regulation actions remains to be established.

Decisions made by drug regulatory agencies require a high level of expertise in statistical methodologies. Without urgent efforts to enhance the level of such expertise in European regulatory agencies, there is a risk that they will not be able to meet emerging challenges such as quantitative modelling of benefit–risk profiles, wider use of innovative trial designs and greater public transparency of clinical trial data.

The problem of counterfeit medicines is increasing rapidly, aggravated by globalization and the lure of profit from this illegal activity. Various types of drugs have been counterfeited, posing a serious public health and safety problem. The current article provides an overview of the issue in Brazil and the resulting measures taken by the National Health Surveillance Agency (ANVISA) in collaboration with the Federal Police from 2007 to March 2011. The study analyzed seizures of counterfeit drugs, arrests, and other factors. No professional pharmacist was present in 90% of the establishments were some type of crime occurred (sale of counterfeit drugs and lack of control of narcotics and other drugs). Among the products seized, most were drugs for erectile dysfunction. The study showed the importance of inter-agency collaboration for combatting this type of irregular drug sales.

Objective: In the United States, per-capita opioid dispensing has increased concurrently with analgesic-related mortality and morbidity since the 1990s. To deter diversion and abuse of controlled substances, most states have implemented electronic prescription drug monitoring programs (PDMPs). We evaluated the impact of state PDMPs on opioid dispensing., Methods: We acquired data on opioids dispensed in a given quarter of the year for each state and the District of Columbia from 1999 to 2008 from the Automation of Reports and Consolidated Orders System and converted them to morphine milligram equivalents (MMEs). We used multivariable linear regression modeling with generalized estimating equations to assess the effect of state PDMPs on per-capita dispensing of MMEs., Results: The annual MMEs dispensed per capita increased progressively until 2007 before stabilizing. Adjusting for temporal trends and demographic characteristics, implementation of state PDMPs was associated with a 3% decrease in MMEs dispensed per capita (p=0.68). The impact of PDMPs on MMEs dispensed per capita varied markedly by state, from a 66% decrease in Colorado to a 61% increase in Connecticut., Conclusions: Implementation of state PDMPs up to 2008 did not show a significant impact on per-capita opioids dispensed. To control the diversion and abuse of prescription drugs, state PDMPs may need to improve their usability, implement requirements for committee oversight of the PDMP, and increase data sharing with neighboring states.

Background: Despite Thailand's commitment to treating people who use drugs as "patients" not "criminals," Thai authorities continue to emphasize criminal law enforcement for drug control. In 2003, Thailand's drug war received international criticism due to extensive human rights violations. However, few studies have since investigated the impact of policing on drug-using populations. Therefore, we sought to examine experiences with policing among people who inject drugs (PWID) in Bangkok, Thailand, between 2008 and 2012., Methods and Findings: Between July 2011 and June 2012, semi-structured, in-depth interviews were conducted with 42 community-recruited PWID participating in the Mitsampan Community Research Project in Bangkok. Interviews explored PWID's encounters with police during the past three years. Audio-recorded interviews were transcribed verbatim, and a thematic analysis was conducted to document the character of PWID's experiences with police. Respondents indicated that policing activities had noticeably intensified since rapid urine toxicology screening became available to police. Respondents reported various forms of police misconduct, including false accusations, coercion of confessions, excessive use of force, and extortion of money. However, respondents were reluctant to report misconduct to the authorities in the face of social and structural barriers to seeking justice. Respondents' strategies to avoid police impeded access to health care and facilitated transitions towards the misuse of prescribed pharmaceuticals. The study's limitations relate to the transferability of the findings, including the potential biases associated with the small convenience sample., Conclusions: This study suggests that policing in Bangkok has involved injustices, human rights abuses, and corruption, and policing practices in this setting appeared to have increased PWID's vulnerability to poor health through various pathways. Novel to this study are findings pertaining to the use of urine drug testing by police, which highlight the potential for widespread abuse of this emerging technology. These findings raise concern about ongoing policing practices in this setting.

The use of thalidomide was never discontinued in Brazil where it is prescribed for leprosy type 2 reaction. Babies with birth defects compatible with the thalidomide embryopathy phenotype were born after 1965, an indication that control on drug dispensing and use failed in the country. The article reports data on thalidomide dispensing and clinical uses in the Federal District in 2011/12, when new rules were put into effect, and data on drug dispensing and use obtained ten years earlier. It was found that the number of patients making use of thalidomide declined from 819 in 2001 to 369 in 2011/12. Leprosy accounted for over 70% of prescriptions in both time periods analyzed in this study. In the same time interval, however, use for lupus erythematosus decreased from 13.7 to 4.9%, while that for multiple myeloma increased from 2.9 to 20.3% of all prescriptions. Thalidomide prescription for the remaining approved indications was far less frequent, and so was the use for off label indications that accounted for <1% of prescriptions in 2001 and 2011/12. Registration of prescribing doctors, patients and dispensing units at the state department of health, apparently rendered this control more effective and reliable.

Aim: to quantify the extent of counterfeit sildenafil in Indonesia., Methods: the study was conducted in 4 big areas: Jakarta, Bandung, East Java (Surabaya and Malang), and Medan. Sildenafil 100 mg tablets were purchased from pharmacies, drugstores, street peddlers, and 3 Indonesian websites. The outlets were chosen by random sampling in each stratum (type of outlet). Sildenafil tablets purchased were sent to Pfizer Quality Operations Division, Dalian, China, for authenticity evaluations (by infra red spectral analysis). All counterfeit tablets were then sent to Pfizer Counterfeit Medicines Laboratory, Sandwich, UK, a portion of which were analyzed quantitatively for sildenafil concentration per tablet (by HPLC)., Results: a total of 518 sildenafil 100 mg tablets were collected and sent to Dalian. Of these tablets, 284 tablets (55%) were genuine sildenafil and 234 tablets (45%) were counterfeit sildenafil. Counterfeit sildenafil were mostly found in street peddlers (100%), in drugstores (56%), and from internet (33%), but pharmacies also had (13%) counterfeit sildenafil. The sildenafil content of 106 counterfeit tablets analyzed varied from 24 to 157 mg per 100 mg tablet. No analysis was done to determine other active ingredient., Conclusion: 45% sildenafil 100 mg tablets in Indonesia were found counterfeit and widely distributed in street peddlers, drugstores, and pharmacies. This report is aimed to alert the potential consumers, health professionals and regulators of this problem.

Objective: To analyze the visa application process and his activity at a tertiary hosipital., Material and Methods: Descriptive study of the drug s visa activity during the period April 2011-April 2012. We designed a database and defined categories on the study variables: patients and recipes. For patients admitted to the Visa Unit, issues detected were recorded based on a previously established classification., Results: 6738 patients were included. They involved the visa of 8,465 recipes. The visa was applied to 170 drugs and nutrition products different, being the majority Tacrolimus. During this period, we detected a total of 420 incidents being the most frequent «No clinical document» (46.67%) and the «Formal completion errors» (28.57%)., Conclusions: This work has allowed a more detailed analysis of the activity, the types of incidents and the identification of areas for improvement., (Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.)

Objectives: Cocaine abuse is widespread in Europe, and Ireland ranks among the leading countries for prevalence of cocaine use among adolescents. This study aimed to examine demographic and substance use correlates of lifetime cocaine use among adolescents with substance use disorder, and to explore the relationship between alcohol intoxication and cocaine initiation., Methods: Data from a cross-sectional study of 171 adolescents presenting to an outpatient substance abuse treatment program in the Dublin metropolitan area were analyzed. Bivariate and multivariate analyses were conducted., Results: Approximately 64% of the participants reported ever used cocaine: 70% reported the first use of cocaine was while alcohol intoxicated and 96% reported the onset of cocaine use was preceded by cannabis use. Later age at treatment entry, unstable accommodation, non engagement in educational/vocational functions, and greater frequency of alcohol and cannabis use had robust associations with lifetime cocaine use. Male gender was significantly associated with first use of cocaine while alcohol intoxicated., Conclusions: Alcohol frequently plays a central role in cocaine initiation in Irish adolescents. Efforts to delay, avoid, or reduce adolescent drinking may yield benefits in terms of reducing cocaine use initiation in this population.

Background: Regulatory decision for withdrawal of a drug from market in European Union (EU) or other developed countries poses a challenge to authorities in developing countries specially when decision varies from different countries, such as for nimesulide., Objectives: To compare and evaluate, benefit and risk data for regulatory action, of nimesulide in India and EU., Methods: Data on Nimesulide from EU available from Report on EMA website and Indian data from published literature (SCOPUS data base), WHO Vigibase and International Medicines Statistics (IMS) was compared., Results: Publications from India on Adverse drug reactions (ADRs) are case reports (10) and case series (14). Drug Utilization Research (DUR) studies (17) are mostly from tertiary centres. Data in the WHO Vigibase is meagre, data from IMS is not easily available and there is regional variation in prescriptions. Thus incidence of ADRs per sale, prescription or defined daily does (DDD) cannot be calculated, as has been done for EU., Conclusion: Limited and varying data in post marketing studies on ADRs and drug utilization for nimesulide from India made regulatory decision difficult. India and other similar countries could contribute to post marketing data for local and global regulatory decisions by systematically planned studies and networking within country and across countries in region.

In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category; Designated Substances in order to more strictly control these substances. In April 2007, 31 compounds and 1 plant were first controlled as Designated Substances. Before 2007, the major compounds distributed in the Japanese illegal drug market were tryptamines, phenethylamines and piperazines. Alkyl nitrites, such as isobutyl nitrite and isopentyl nitrite, were also widely distributed. After they were listed as Narcotics or Designated Substances in 2007, these compounds, especially the tryptamines, quickly disappeared from the market. In their place, cathinone derivatives have been widely distributed, as well as different phenethylamines and piperazines. Additionally, in recent years, new herbal products containing synthetic cannabinoids have appeared globally. As at July 2012, 78 substances (including 1 plant; Salvia divinorum) were listed in the category of Designated Substances. They were 13 tryptamines, 17 phenethylamines, 11 cathinones, 4 piperazines, 23 synthetic cannabinoids, 6 alkyl nitrites, 3 other compounds and 1 plant. In this review, we show our survey of the spread of new designer drugs in Japan, focusing especially on synthetic cannabinoids and cathinone derivatives. Also, the prevalence and legal status of these substances in other countries will be presented.

Background: In August 2010, a tamper-resistant formulation of controlled-release oxycodone (OxyContin-OP) was introduced in the United States but not in Canada. Our objective was to determine whether introduction of OxyContin-OP in the United States influenced prescription volumes for the original controlled-release oxycodone formulation (OxyContin) at Canadian pharmacies near the international border., Methods: We conducted a population-based, serial, cross-sectional study of prescriptions dispensed from pharmacies in the 3 cities with the highest volume of US-Canada border crossings in Ontario: Niagara Falls, Windsor and Sarnia. We analyzed data on all outpatient prescriptions for OxyContin dispensed by Canadian pharmacies near each border crossing between 2010 Apr. 1 and 2012 Feb. 29. We calculated and compared monthly prescription rates, adjusted per 1000 population and stratified by tablet strength., Results: The number of tablets dispensed near 4 border crossings in the 3 Canadian cities remained stable over the study period. However, the rate of dispensing at pharmacies near the Detroit-Windsor Tunnel increased roughly 4-fold between August 2010 and February 2011, from 505 to 1969 tablets per 1000 population. By April 2011, following warnings to prescribers and pharmacies regarding drug-seeking behaviour, the dispensing rate declined to 1683 tablets per 1000 population in this area. By November 2011, the rate had returned to levels observed in early 2010. Our analyses suggest that 242 075 excess OxyContin tablets were dispensed near the Detroit-Windsor Tunnel between August 2010 and October 2011., Conclusions: Prescribing of the original formulation of controlled-release oxycodone rose substantially near a major international border crossing following the introduction of a tamper-resistant formulation in the United States. It is possible that the restriction of this finding to the area surrounding the Detroit-Windsor Tunnel reflects specific characteristics of this border crossing, including its high traffic volume, direct access to the downtown core and drug-trafficking patterns in the Detroit area. Our findings highlight the potential impact of cross-border differences in medication availability on drug-seeking behaviour.