Faculty Bibliography

BACKGROUND:The endocannabinoid system has been implicated in physiological processes fundamental to pain, giving plausibility to the hypothesis that cannabis may be used as a substitute or complement to prescription opioids in the management of chronic pain. We examined the association of medical cannabis licensure with likelihood of prescription opioid receipt using administrative records. METHODS:This study linked registry information for medical cannabis licensure with records from the prescription drug monitoring program from April 1, 2016 to March 31, 2019 to create a population-based, retrospective cohort in Rhode Island. We examined within-person changes in receipt of any opioid prescription and receipt of an opioid prescription with a morphine equivalent dose of 50 mg or more, and of 90 mg or more. RESULTS:The sample included 5,296 participants with medical cannabis license. Medical cannabis licensure was not associated with the odds of filling any opioid prescription (OR: 0.99; 95% CI: 0.94-0.1.05) or the odds of filling a prescription with a morphine equivalent dose of 50 mg or more (OR: 0.93; 95% CI: 0.84-1.04) and 90 mg or more (OR: 0.99; 95% CI: 0.86-1.15). CONCLUSION/CONCLUSIONS:Medical cannabis licensure was not associated with subsequent cessation and reduction in prescription opioid use. Re-scheduling of cannabis will allow for the conduct of randomized controlled trials to determine the efficacy of medical cannabis as an alternative to prescription opioid use or a complement to the use of lower doses of prescription opioids in patients with chronic pain.

BACKGROUND:Variation in drug policies, norms, and substance use over time and across countries may affect the normative sequences of adolescent substance use initiation. We estimated relative and absolute time-varying associations between prior alcohol and tobacco use and adolescent marijuana initiation in Argentina and Chile. Relative measures quantify the magnitude of the associations, whereas absolute measures quantify excess risk. METHODS:We analyzed repeated, cross-sectional survey data from the National Surveys on Drug Use Among Secondary School Students in Argentina (2001-2014) and Chile (2001-2017). Participants included 8th, 10th, and 12th grade students (N = 680,156). Linear regression models described trends over time in the average age of first use of alcohol, tobacco, and marijuana. Logistic regression models were used to estimate time-varying risk ratios and risk differences of the associations between prior alcohol and tobacco use and current-year marijuana initiation. RESULTS:Average age of marijuana initiation increased and then decreased in Argentina and declined in Chile. In both countries, the relative associations between prior tobacco use and marijuana initiation weakened amid declining rates of tobacco use; e.g., in Argentina, the risk ratio was 19.9 (95% CI: 9.0-30.8) in 2001 and 11.6 (95% CI: 9.0-13.2) in 2014. The relative association between prior alcohol use and marijuana initiation weakened Chile, but not in Argentina. On the contrary, risk differences (RD) increased substantially across both relationships and countries, e.g., in Argentina, the RD for tobacco was 3% (95% CI: 0.02-0.03) in 2001 and 12% (95% CI: 0.11-0.13) in 2014. CONCLUSION/CONCLUSIONS:Diverging trends in risk ratios and risk differences highlight the utility of examining multiple measures of association. Variation in the strength of the associations over time and place suggests the influence of environmental factors. Increasing risk differences indicate alcohol and tobacco use may be important targets for interventions to reduce adolescent marijuana use.

Importance/UNASSIGNED:Prescription opioids are involved in more than half of opioid overdoses among younger persons. Understanding opioid prescribing practices is essential for developing appropriate interventions for this population. Objective/UNASSIGNED:To examine temporal trends in opioid prescribing practices in children, adolescents, and younger adults in the US from 2006 to 2018. Design, Setting, and Participants/UNASSIGNED:A population-based, cross-sectional analysis of opioid prescription data was conducted from January 1, 2006, to December 31, 2018. Longitudinal data on retail pharmacy-dispensed opioids for patients younger than 25 years were used in the analysis. Data analysis was performed from December 26, 2019, to July 8, 2020. Main Outcomes and Measures/UNASSIGNED:Opioid dispensing rate, mean amount of opioid dispensed in morphine milligram equivalents (MME) per day (individuals aged 15-24 years) or MME per kilogram per day (age <15 years), duration of prescription (mean, short [≤3 days], and long [≥30 days] duration), high-dosage prescriptions, and extended-release or long-acting (ER/LA) formulation prescriptions. Outcomes were calculated for age groups: 0 to 5, 6 to 9, 10 to 14, 15 to 19, and 20 to 24 years. Joinpoint regression was used to examine opioid prescribing trends. Results/UNASSIGNED:From 2006 to 2018, the opioid dispensing rate for patients younger than 25 years decreased from 14.28 to 6.45, with an annual decrease of 15.15% (95% CI, -17.26% to -12.99%) from 2013 to 2018. The mean amount of opioids dispensed and rates of short-duration and high-dosage prescriptions decreased for all age groups older than 5 years, with the largest decreases in individuals aged 15 to 24 years. Mean duration per prescription increased initially for all ages, but then decreased for individuals aged 10 years or older. The duration remained longer than 5 days across all ages. The rate of long-duration prescriptions increased for all age groups younger than 15 years and initially increased, but then decreased after 2014 for individuals aged 15 to 24 years. For children aged 0 to 5 years dispensed an opioid, annual increases from 2011 to 2014 were noted for the mean amount of opioids dispensed (annual percent change [APC], 10.58%; 95% CI, 1.77% to 20.16%) and rates of long-duration (APC, 30.42%; 95% CI, 14.13% to 49.03%), high-dosage (APC, 31.27%; 95% CI, 16.81% to 47.53%), and ER/LA formulation (APC, 27.86%; 95% CI, 12.04% to 45.91%) prescriptions, although the mean amount dispensed and rate of high-dosage prescriptions decreased from 2014 to 2018. Conclusions and Relevance/UNASSIGNED:These findings suggest that opioid dispensing rates decreased for patients younger than 25 years, with decreasing rates of high-dosage and long-duration prescriptions for adolescents and younger adults. However, opioids remain readily dispensed, and possible high-risk prescribing practices appear to be common, especially in younger children.

BACKGROUND AND AIMS/OBJECTIVE:Persons with substance use disorders (SUDs) are at elevated risk of suicide death. We identified novel risk factors and interactions that predict suicide among men and women with SUD using machine learning. DESIGN/METHODS:Case-cohort study. SETTING/METHODS:Denmark. PARTICIPANTS/METHODS:The sample was restricted to persons with their first SUD diagnosis during 1995 to 2015. Cases were persons who died by suicide in Denmark during 1995 to 2015 (n = 2774) and the comparison subcohort was a 5% random sample of individuals in Denmark on 1 January 1995 (n = 13 179). MEASUREMENTS/METHODS:Suicide death was recorded in the Danish Cause of Death Registry. Predictors included social and demographic information, mental and physical health diagnoses, surgeries, medications, and poisonings. FINDINGS/RESULTS:Persons among the highest risk for suicide, as identified by the classification trees, were men prescribed antidepressants in the 4 years before suicide and had a poisoning diagnosis in the 4 years before suicide; and women who were 30+ years old and had a poisoning diagnosis 4 years before and 12 months before suicide. Among men with SUD, the random forest identified five variables that were most important in predicting suicide; reaction to severe stress and adjustment disorders, drugs used to treat addictive disorders, age 30+ years, antidepressant use, and poisoning in the 4 prior years. Among women with SUD, the random forest found that the most important predictors of suicide were prior poisonings and reaction to severe stress and adjustment disorders. Individuals in the top 5% of predicted risk accounted for 15% of all suicide deaths among men and 24% of all suicides among women. CONCLUSIONS:In Denmark, prior poisoning and comorbid psychiatric disorders may be among the most important indicators of suicide risk among persons with substance use disorders, particularly among women.

INTRODUCTION/BACKGROUND:Traditional treatment programs for substance use disorder (SUD) tend to be male-dominated environments, which can negatively affect women's access to treatment and related outcomes. Women's specific treatment needs have led some providers to develop women-only SUD treatment programs in several countries. In Chile, women-only programs were only fully implemented in 2010. We compared treatment outcomes and readmission risk for adult women admitted to state-funded women-only versus mixed-gender SUD treatment programs in Chile. METHODS:We used a registry-based retrospective cohort design of adult women in women-only (N = 8200) and mixed-gender (N = 13,178) SUD treatment programs from 2010 to 2019. The study obtained data from the National Drug and Alcohol Service from Chile. We used a multistate model to estimate the probabilities of experiencing treatment completion, discharge without completion (i.e., patient-initiated discharge and administrative discharge), or readmission, as well as the likelihood of being readmitted, conditioned on prior treatment outcome. We adjusted models for multiple baseline characteristics (e.g., substance use, socioeconomic). RESULTS:Overall, 24% of women completed treatment and 54% dropped out of treatment. The proportion of patient-initiated discharges within the first three month was larger in women-only than in mixed-gender programs (19% vs. 12%). In both programs, women who completed treatment were more likely to experience readmission at three months, and one and three years. In the long term, women in the women-only programs were more likely to complete treatment than women in mixed-gender programs (34% vs. 23%, respectively). The readmission probability was higher among women who previously completed treatment than those who had a discharge without completion (40% vs 21% among women in women-only programs; 38% vs. 19% among women in mixed-gender programs, respectively); no differences occurred in the risk of readmission between women-only and mixed-gender programs. CONCLUSIONS:In terms of treatment outcomes and readmission risk, women-only programs had similar results to mixed-gender programs in Chile. The added value of these specialized programs should be addressed in further research.

Importance:The rate of deaths from overdose has increased during the COVID-19 pandemic, and recent US overdose mortality rates have been markedly high. However, scant data are available on the causes of this increase or subpopulations at elevated risk. Objective:To evaluate the rates and characteristics of deaths from drug overdose before vs during the COVID-19 pandemic. Design, Setting, and Participants:This retrospective, population-based cohort study used data from 4 statewide databases linked at the person level via the Rhode Island Data Ecosystem on adults with deaths due to overdose in Rhode Island from January 1 to August 31, 2019, and January 1 to August 31, 2020. Main Outcomes and Measures:The rates of unintentional deaths from drug-related overdose during the 2019 and 2020 observation periods overall and by sociodemographic characteristics, drugs contributing to the cause of death, location of death, and socioeconomic factors were evaluated. In subgroup analyses restricted to Medicaid beneficiaries (n = 271), the proportions of deaths from overdose by behavioral health treatment and diagnosis claims in the year before death were also examined. Results:A total of 470 adults who died of drug overdose were included in the analysis (353 men [75%]; mean [SD] age, 43.5 [12.1] years). The rate of deaths from overdose in Rhode Island increased 28.1%, from 29.2 per 100 000 person-years in 2019 to 37.4 per 100 000 person-years in 2020 (P = .009). Compared with 2019, rates of deaths due to overdose during 2020 were higher among men (43.2 vs 59.2 per 100 000 person-years; P = .003), non-Hispanic White individuals (31.0 vs 42.0 per 100 000 person-years; P = .005), single individuals (54.8 vs 70.4 per 100 000 person-years; P = .04), deaths involving synthetic opioids (20.8 vs 28.3 per 100 000 person-years; P = .005), and deaths occurring in a personal residence (13.2 vs 19.7 per 100 000 person-years; P = .003). A decrease in the proportion of deaths from overdose involving heroin (11 of 206 [5%] vs <2% [exact value suppressed]; P = .02) and an increase among persons experiencing job loss (16 of 206 [8%] vs 41 of 264 [16%]; P = .01) from 2019 to 2020 were observed. Among individuals who died of overdose and were Medicaid beneficiaries, the proportions of those aged 50 to 59 years with anxiety (11 of 121 [9%] vs 29 of 150 [19%]; P = .03), men with depression (27 of 121 [22%] vs 57 of 150 [38%]; P = .008), and men with anxiety (28 of 121 [23%] vs 55 of 150 [37%]; P = .02) increased during 2020 compared with 2019. Conclusions and Relevance:In this cohort study, during the first 8 months of 2020, the rate of deaths from overdose increased in Rhode Island compared with the same period in 2019, and several emerging characteristics of deaths from drug overdose during the first year of the COVID-19 pandemic were identified. These findings may inform interventions that address macroenvironmental changes associated with the pandemic.

OBJECTIVE:Suicidal ideation and plans are increasing among US adolescents. Changing prevalence of online victimization is frequently hypothesized as an explanation for this increase. We tested trends in online and offline victimization and whether they contribute to recent trends in adolescent suicidal outcomes. METHODS:= 73 074) were collected biennially through national cross-sectional surveys of US school-attending adolescents. We examined trends in past-year victimization. We also examined whether the relationship between victimization and past-year suicidal ideation, plans, attempts, and injury changed over time using survey-weighted logistic regressions that adjusted for sex and race and ethnicity. We also sex-stratified results to examine sex differences. RESULTS:Although suicidal ideation and plans increased among US adolescents (mainly girls), online and offline victimization prevalence did not increase over time (offline: 20.0% in 2011, 19.5% in 2019; online: 16.2% in 2011, 15.7% in 2019). Online and offline victimization were associated with suicidal outcomes, especially co-occurring online and offline victimization (eg, adjusted odds ratio [co-occurring online and offline victimization versus none, outcome: suicidal injury] = 8.37; 95% confidence interval: 7.06-9.91). The magnitude of the associations between victimization and suicidal outcomes largely remained stable over time. CONCLUSION/CONCLUSIONS:Peer victimization prevalence has not sufficiently changed over time in concert with suicidal outcomes to explain increased suicidal outcomes. The prevalence of victimization has remained relatively invariant across time despite growing awareness and programming, making online and offline victimization consistent, socially-patterned risk factors that warrant further monitoring and interventions. Research must examine risk factors beyond victimization to explain increasing suicidal outcomes.

OBJECTIVE/UNASSIGNED:The authors sought to estimate the prevalence of past-12-month and lifetime cannabis use and cannabis use disorder among U.S. veterans; to describe demographic, substance use disorder, and psychiatric disorder correlates of nonmedical cannabis use and cannabis use disorder; and to explore differences in cannabis use and cannabis use disorder prevalence among veterans in states with and without medical marijuana laws. METHODS/UNASSIGNED:Participants were 3,119 respondents in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) who identified as U.S. veterans. Weighted prevalences were calculated. Logistic regression analyses tested associations of nonmedical cannabis use and cannabis use disorder with demographic and clinical correlates and examined whether prevalence differed by state legalization status. RESULTS/UNASSIGNED:The prevalences of any past-12-month cannabis use and cannabis use disorder were 7.3% and 1.8%, respectively. Lifetime prevalences were 32.5% and 5.7%, respectively. Past-12-month and lifetime cannabis use disorder prevalence estimates among nonmedical cannabis users were 24.4% and 17.4%, respectively. Sociodemographic correlates of nonmedical cannabis use and use disorder included younger age, male gender, being unmarried, lower income, and residing in a state with medical marijuana laws. Nonmedical cannabis use and use disorder were associated with most psychiatric and substance use disorders examined. CONCLUSIONS/UNASSIGNED:Among veterans, the odds of nonmedical cannabis use and use disorder were elevated among vulnerable subgroups, including those with lower income or psychiatric disorders and among survey participants residing in states with medical marijuana laws. The study findings highlight the need for clinical attention (e.g., screening, assessment) and ongoing monitoring among veterans in the context of increasing legalization of cannabis.

BACKGROUND:Maintenance treatments with medications for opioid use disorder (MOUD) are highly effective at reducing overdose risk while patients remain in care. However, few patients initiate medication and retention remains a critical challenge across settings. Much remains to be learned about individual and structural factors that influence successful retention, especially among populations dispensed MOUD in outpatient settings. METHODS:We examined individual and structural characteristics associated with MOUD treatment retention among a national sample of adults seeking MOUD treatment in outpatient substance use treatment settings using the 2017 Treatment Episode Dataset-Discharges (TEDS-D). The study assessed predictors of retention in MOUD using multivariate logistic regression and accelerated time failure models. RESULTS:Of 130,300 episodes of MOUD treatment in outpatient settings, 36% involved a duration of care greater than six months. The strongest risk factors for treatment discontinuation by six months included being of younger age, ages 18-29 ((OR):0.52 [95%CI:0.50-0.54]) or 30-39 (OR:0.57 [95%CI:0.55-0.59); experiencing homelessness (OR: 0.70 [95%CI:0.66-0.73]); co-using methamphetamine (OR:0.48 [95%CI:0.45-0.51]); and being referred to treatment by a criminal justice source (OR:0.55 [95%CI:0.52-0.59) or by a school, employer, or community source (OR:0.71 [95%CI:0.66-0.76). CONCLUSIONS:Improving retention in treatment is a pivotal stage in the OUD cascade of care and is critical to reducing overdose deaths. Efforts should prioritize interventions to improve retention among patients who are both prescribed and dispended MOUD, especially youth, people experiencing homelessness, polysubstance users, and people referred to care by the justice system who have especially short stays in care.