Showing papers in "Addiction in 2018"

Global statistics on alcohol, tobacco and illicit drug use: 2017 status report

Abstract: Amy Peacock, Janni Leung, Sarah Larney, Samantha Colledge, Matthew Hickman, Jurgen Rehm, Gary A. Giovino, Robert West, Wayne Hall, Paul Griffiths, Robert Ali, Linda Gowing, John Marsden, Alize J. Ferrari, Jason Grebely, Michael Farrell and Louisa Degenhardt

Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis.

Abstract: AIMS: To estimate the effects of needle syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of Hepatitis C virus (HCV) in people who inject drugs (PWID). METHODS: Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥100% coverage (receiving sufficient or greater number of needles/syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomised studies tool. Random effects models were used in meta-analysis. RESULTS: We identified 28 studies (n=6279) in North America (13), UK (5), Europe (4), Australia (5), and China (1). Studies were at moderate (2), serious (17) critical (7) and non-assessable risk of bias (2). Current OST is associated with 50% (risk ratio (RR) 0.50 95% CI 0.40-0.63) reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I(2) =0, p=0.889). Weaker evidence was found for high NSP coverage (RR=0.79 95% CI 0.39-1.61) with high heterogeneity (I(2) =77%, p=0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR=0.44, 95% CI 0.24-0.80) with low heterogeneity (I(2) =12.3%, p=0.337) but not in North America (RR=1.58, I(2) =89.5%, p=<0.001). Combined OST/NSP is associated with a 76% reduction in HCV acquisition risk (RR=0.24 95% CI=0.07-0.89, I(2) =80% p=0.007). According to GRADE criteria, the evidence on OST and combined OST/NSP is low quality while NSP is very low. CONCLUSIONS: Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle syringe programmes. There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe.

All drinking is not equal: how a social practice theory lens could enhance public health research on alcohol and other health behaviours

Abstract: Background The social meanings, settings and habitual nature of health-related activities and their integration into our daily lives are often overlooked in quantitative public health research. This reflects an overly individualized approach to epidemiological surveillance and evaluations of public health interventions, based on models of behaviour that are rooted in social cognition and rational choice theories. This paper calls for a new approach to alcohol epidemiology and intervention research informed by theories of practice. Argument Practices are conceptualized as routinized types of human activity that are made up of, and can be recognized by, the coming together of several interwoven elements in the same situation (e.g. materials, meanings, skills, locations, timings). Different practices are interconnected—they can occur simultaneously (e.g. drinking and eating), hold each other in place (e.g. after-work drinks) or compete for time (e.g. parenting versus socializing). Applying these principles to alcohol research means shifting attention away from individuals and their behaviours and instead making drinking practices an important unit of analysis. Studying how drinking practices emerge, persist and decay over time, how they spread through populations and local or social networks and how they relate to other activities of everyday life promises new insights into how, why, where, when and with whom drinking and getting drunk occur. Conclusions Theories of practice provide a framework for generating new explanations of stability and change in alcohol consumption and other health behaviours. This framework offers potential for novel insights into the persistence of health inequalities, unanticipated consequences of policies and interventions and new interventions targets through understanding which elements of problematic practices are likely to be most modifiable. We hope this will generate novel insights into the emergence and decay of drinking practices over time and into the geographical and socio-demographic patterning of drinking. Theories of practice-informed research would consider how alcohol policies and population-level interventions might differentially affect different drinking practices.

Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta-analysis

Abstract: Aims To conduct a systematic review and meta-analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past-month marijuana use prevalence among adolescents. Methods A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta-analyzed. Estimates of MML effects on any past-month marijuana use prevalence from included studies were obtained from comparisons of pre–post MML changes in MML states to changes in non-MML states over comparable time-periods. These estimates were standardized and entered into a meta-analysis model with fixed-effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F-test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non-MML states for marijuana use prevalence among adolescents. The meta-analysis yielded a non-significant pooled estimate (standardized mean difference) of −0.003 (95% confidence interval = −0.012, +0.007). Four studies compared MML with non-MML states on pre-MML differences and all found higher rates of past-month marijuana use in MML states pre-MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non-significant results, although limited heterogeneity may warrant further study. Conclusions Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.

Extended-release injectable naltrexone for opioid use disorder: a systematic review.

Abstract: Aims To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined. Methods We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included. Results We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification. Conclusions Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.

Alcohol industry involvement in policymaking: a systematic review.

Abstract: AIMS: To summarize the substantive findings of studies of alcohol industry involvement in national or supranational policymaking, and to produce a new synthesis of current evidence. METHODS: This study examined peer-reviewed journal reports published in the English language between 1980 and 2016 of studies of alcohol industry involvement in policymaking. Included studies were required to provide information on data collection and analysis and to have sought explicitly to investigate interventions by alcohol industry actors within the process of public policymaking. Eight electronic databases were searched on 27 February 2017. The methodological strengths and limitations of individual studies and the literature as a whole were examined. A thematic synthesis using an inductive approach to the generation of themes was guided by the research aims and objectives. RESULTS: Twenty reports drawn from 15 documentary and interview studies identify the pervasive influence of alcohol industry actors in policymaking. This evidence synthesis indicates that industry actors seek to influence policy in two principal ways by: (1) framing policy debates in a cogent and internally consistent manner, which excludes from policy agendas issues that are contrary to commercial interests; and (2) adopting short- and long-term approaches to managing threats to commercial interests within the policy arena by building relationships with key actors using a variety of different organizational forms. This review pools findings from existing studies on the range of observed impacts on national alcohol policy decision-making throughout the world. CONCLUSIONS: Alcohol industry actors are highly strategic, rhetorically sophisticated and well organized in influencing national policymaking.

Corrected US opioid-involved drug poisoning deaths and mortality rates, 1999-2015.

Abstract: Background and Aims Most prior estimates of opioid-involved drug poisoning mortality counts or rates are understated because the specific drugs leading to death are frequently not identified on death certificates. This analysis provides corrected national estimates of opioid and heroin/synthetic opioid-involved counts and mortality rates, as well as changes over time in them from 1999 to 2015. Methods Data on drug poisoning deaths to US residents from 1999 to 2015, obtained from the Centers for Disease Control and Prevention (CDC) Multiple Cause of Death (MCOD) files, were used with the drugs involved in fatal overdoses imputed when not identified on the death certificates. Results The official CDC figure that 33 091 drug deaths involved opioids in 2015 is an undercount, with the actual number being approximately 39 999. Corrected counts and rates of any opioid and heroin/synthetic opioid-involved drug deaths are 20–35% higher in every year than reported figures. The corrections almost always raise the changes estimated to have occurred since 1999, with the largest differences observed in 2011 for any opioids (5677 deaths and 1.7 per 100 000) and in 2015 for heroin/synthetic opioids (3228 deaths and 1.0 per 100 000). However, percentage growth since 1999 is sometimes slower when based on corrected rather than reported fatality data, and with sensitivity to the choice of base years. Conclusions Death certificate reports understate the prevalence of and changes over time in opioid and heroin/synthetic opioid-involved drug mortality in the United States. Adjustments imputing the drugs involved for cases where none are identified on the death certificates are likely to provide more accurate estimates.

Gateway effects and electronic cigarettes

Abstract: Background E-cigarettes are alleged to be a gateway to cigarette smoking in non-smokers. This study examines whether the gateway theory has value, whether the criteria to establish causality have been met and what type of evidence is required to test this theory. Analysis Experiments are impractical, and we may not be able to test properly the gateway effects via observational studies that simply adjust for confounders. Multivariate models cannot eliminate all the variance in propensity to smoke captured by the variable ‘vaping’ because of the proximity of these two behaviours. It may be difficult to prove that vaping precedes smoking when product use co-occurs and when, in fact, smoking usually precedes vaping. The gateway theory is not compatible with either (1) the decrease in smoking prevalence observed in adolescents in countries where vaping increased or (2) an increase in smoking among teenagers after age restrictions were imposed on e-cigarette purchases. A spurious gateway effect can be produced artificially by mathematical models in which a propensity to use substances is correlated with opportunities to use substances. Finally, neither nicotine medications nor smokeless tobacco produce gateway effects. Available data are compatible with a common liability model in which people who are liable to use nicotine are more likely to use both e-cigarettes and cigarettes. Conclusions Despite its weaknesses and scant empirical support, the gateway theory of smoking initiation has had enormous political influence. Policies based on this theory will not have the intended effects if the association between vaping and smoking is explained by common liabilities.

The effect of a behavioral activation treatment for substance use on post‐treatment abstinence: a randomized controlled trial

Abstract: Aims To compare outcomes for a behavioral activation group treatment for substance use [life enhancement treatment for substance use (LETS ACT)] versus a time and group size-matched control condition delivered in a residential treatment setting. Design Single-site two-arm parallel-group randomized clinical trial with follow-up assessment at 3, 6 and 12 months post-treatment. Setting Residential substance use treatment facility in the United States. Participants Participants were 263 adults [mean age 42.7 (11.8); 29.5% female; 95.4% African American; 73.2% court mandated] whose insurance dictated 30-day (65.9%) or 90-day (34.1%) treatment duration. Intervention and comparator LETS ACT (n = 142) is a treatment developed originally for depression and modified for substance use. It teaches participants to increase positively reinforcing value-driven activities in order to counter depression and relapse. The control group [supportive counseling (SC); n = 121] received time and group size-matched supportive counseling. Treatment was delivered in five or eight 1-hour sessions depending on patient length of stay. Measurements Percentage abstinent at follow-up, percentage of substance use days among those reporting use, depressive symptoms [Beck Depression Inventory (BDI)] and adverse consequences of drug use [Short Inventory of Problems-Alcohol and Drug (SIP-AD)]. Findings LETS ACT had significantly higher abstinence rates at 3 months [odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.3-3.7], 6 months (OR = 2.6, 95% CI= 1.3-5.0) and 12 months (OR = 2.9, 95% CI = 1.3-6.1) post-treatment compared with SC. LETS ACT participants reported significantly fewer adverse consequences from substance use at 12 months post-treatment [B = 4.50, standard error (SE) = 2.17, 95% CI = 0.22-8.78]. Treatment condition had no effect on percentage substance use days among those who resumed use or on change in depressive symptoms; the latter decreased over time only in those who remained abstinent after residential treatment irrespective of condition (B = 0.43, SE = 0.11, 95% confidence interval = 0.22-0.65). Conclusions A behavioral activation group treatment for substance use (LETS ACT) appears to increase the likelihood of abstinence and reduce adverse consequences from substance use up to 12 months post-treatment.

‘Are The Times A‐Changin’? Trends in adolescent substance use in Europe

Abstract: AIMS: To estimate temporal trends in adolescents' current cigarette, alcohol and cannabis use in Europe by gender and region, test for regional differences, and evaluate regional convergence. DESIGN AND SETTING: Five waves of the European School Survey Project on Alcohol and Other Drugs (ESPAD) from 28 countries between 1999 and 2015. Countries were grouped into five regions (Northern (NE), Southern (SE), Western (WE), Eastern Europe (EE), the Balkans (BK)). PARTICIPANTS: A total of 223,814 male and 211,712 female 15- to 16-year old students. MEASUREMENTS: Daily cigarette use, weekly alcohol use, monthly heavy episodic drinking (HED), and monthly cannabis use. Linear and quadratic trends were tested using multilevel mixed-effects logistic regression; regional differences were tested using pairwise Wald tests; mean absolute differences (MD) of predicted prevalence were used for evaluating conversion. FINDINGS: Daily cigarette use among boys in EE showed a declining curvilinear trend, whereas in all other regions a declining linear trend was found. With the exception of BK, trends of weekly drinking decreased curvilinear in both genders in all regions. Among girls, trends in WE, EE and BK differed from trends in NE and SE. Monthly HED showed increasing curvilinear trends in all regions except in NE (both genders), WE and EE (boys each). In both genders, the trend in EE differed from the trend in SE. Trends of cannabis use increased in both genders in SE and BK; differences were found between the curvilinear trends in EE and BK. MD by substance and gender were generally rather stable over time. CONCLUSIONS: Despite regional differences in prevalence of substance use among European adolescents from 1999 to 2015, trends showed remarkable similarities with strong decreasing trends in cigarette use and moderate decreasing trends in alcohol use. Trends of cannabis use only increased in Southern Europe and the Balkans. Trends across all substance use indicators suggest no regional convergence.

Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate

Abstract: Background and aims - Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication. Design - Systematic review with direct and network meta-analysis of double-blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non-abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data. Setting - Thirty-two RCTs. Participants - A total of 6036 patients. Measurements - The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes. Findings - No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I = 0%], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor. Conclusions - There is currently no high-grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes.

Baclofen: its effectiveness in reducing harmful drinking, craving, and negative mood. A meta-analysis.

Abstract: Background and aims There are a limited number of pharmacotherapies licensed for alcohol use disorders (AUDs). Baclofen is a γ-aminobutyric acid B (GABA-B) agonist which is used increasingly as an off-label treatment. A meta-analysis of randomized controlled trials (RCTs) was conducted to determine the efficacy of baclofen in reducing drinking behaviour, craving, depression and anxiety compared with placebo. Methods Random-effects meta-analyses were computed on outcome data from 12 RCTs comparing baclofen with placebo. Included RCTs provided data on at least one of the primary outcome measures (drinking-related: heavy drinking days, abstinent days, abstinence rates) or secondary outcome measures (craving, anxiety, depression). Results Baclofen had a significant effect on abstinence rates when using intention-to-treat analysis [total n baclofen = 307, total n control = 283: odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.03, 6.93; Z = 2.01, P = 0.04, I2 = 76%, number needed to treat = 8]. No other significant effects of treatment efficacy [e.g. heavy drinking days: standardized mean differences (SMD) = -0.26, 95% CI = -0.68, 0.15; Z = 1.24, P = 0.21, I2 = 95%] or mechanism of action (e.g. craving: SMD = -0.13, 95% CI = -0.36, 0.09; Z = 1.18, P = 0.24, I2 = 87%) were observed. There was substantial heterogeneity in effect sizes across each analysis. Conclusions As a treatment for alcohol use disorders, baclofen is associated with higher rates of abstinence than placebo. However, there is no superior effect of baclofen on increasing number of abstinent days, or decreasing heavy drinking, craving, anxiety or depression. These results suggest that the current increasing use of baclofen as a treatment for alcohol use disorders is premature.

Predictors of smoking cessation during pregnancy: a systematic review and meta-analysis.

Abstract: AIM: To identify factors found in the research literature to be associated with smoking cessation in pregnancy. METHODS: Electronic searches of the bibliographic databases of PubMed, EMBASE, PsycINFO, Elsevier, Scopus and ISI Web of Science were conducted to April 2017. All studies reporting factors associated with smoking cessation or continuing smoking during pregnancy were included and reviewed systematically, irrespective of study design. The Newcastle-Ottawa Quality Assessment Scale was used to assess the study quality. The DerSimonian & Laird random-effects model was used to conduct meta-analyses, and where effect estimates were reported for factors included in at least three studies. RESULTS: Fifty-four studies, including 505 584 women globally who smoked before pregnancy, 15 clinical trials and 40 observational studies, were included in the review and 36 (65.5%) were considered to be of high quality. This review identified 11 socio-demographic, seven socially related, 19 smoking behaviour-related, five pregnancy-related, six health-related and six psychological factors that were associated significantly with smoking cessation during pregnancy. The most frequently observed significant factors associated with cessation were: higher level of education, pooled odds ratio (OR), 95% confidence interval (CI) = 2.16 (1.80-2.84), higher socio-economic status: 1.97 (1.20-3.24), overseas maternal birth: 2.00 (1.40-2.84), Medicaid coverage or private insurance: 1.54 (1.29-1.85), living with partner or married: 1.49 (1.38-1.61), partner/other members of the household do not smoke: 0.42 (0.35-0.50), lower heaviness of smoking index score: 0.45 (0.27-0.77, lower baseline cotinine level: 0.78 (0.64-0.94), low exposure to second-hand smoking: 0.45 (0.20-1.02), not consuming alcohol before and/or during pregnancy: 2.03 (1.47-2.80), primiparity: 1.85 (1.68-2.05), planned breastfeeding:1.99 (1.94-2.05), perceived adequate pre-natal care: 1.74 (1.38-2.19), no depression: 2.65 (1.62-4.30) and low stress during pregnancy: 0.58 (0.44-0.77). CONCLUSION: A wide range of socio-demographics, relationship, social, smoking-related, pregnancy-related, health and psychological factors have been found to predict smoking cessation in pregnancy.

Gendered violence and overdose prevention sites: a rapid ethnographic study during an overdose epidemic in Vancouver, Canada

Abstract: Background and aims North America's overdose epidemic is increasingly driven by fentanyl and fentanyl-adulterated drugs. Supervised consumption sites, including low-threshold models (termed overdose prevention sites; OPS), are now being debated in the United States and implemented in Canada. Despite evidence that gendered and racialized violence shape access to harm reduction among women who use drugs (WWUD), this has not been examined in relation to OPS and amid the overdose epidemic. This study explores how overlapping epidemics of overdose and gendered and racialized violence in Vancouver's Downtown Eastside, one of North America's overdose epicenters, impacts how marginalized WWUD experience OPS. Design Qualitative analysis using rapid ethnographic fieldwork. Data collection included 185 hours of naturalistic observation and in-depth interviews; data were analyzed thematically using NVivo. Setting Vancouver, Canada. Participants Thirty-five WWUD recruited from three OPS. Measurements Participants' experiences of OPS and the public health emergency. Findings The rapid onset and severity of intoxication associated with the use of fentanyl-adulterated drugs in less regulated drug use settings not only amplified WWUD's vulnerability to overdose death but also violence. Participants characterized OPS as safer spaces to consume drugs in contrast to less regulated settings, and accommodation of assisted injections and injecting partnerships was critical to increasing OPS access among WWUD. Peer-administered injections disrupted gendered power relations to allow women increased control over their drug use; however, participants indicated that OPS were also gendered and racialized spaces that jeopardized some women's access. Conclusion Although women who use drugs in Vancouver, Canada appear to feel that overdose prevention sites address forms of everyday violence made worse by the overdose epidemic, these sites remain 'masculine spaces' that can jeopardize women's access.

Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co‐twin control study

Abstract: Aims This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation. Design A longitudinal co-twin control study. Setting and Participants Participants were 1989 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994 to 1995. Measurements Frequency of cannabis use and cannabis dependence were assessed at age 18. Intelligence quotient (IQ) was obtained at ages 5, 12 and 18. Executive functions were assessed at age 18. Findings Compared with adolescents who did not use cannabis, adolescents who used cannabis had lower IQ in childhood prior to cannabis initiation and lower IQ at age 18, but there was little evidence that cannabis use was associated with IQ decline from ages 12–18. For example, adolescents with cannabis dependence had age 12 and age 18 IQ scores that were 5.61 (t = −3.11, P = 0.002) and 7.34 IQ points (t = −5.27, P 0.10). The one exception was that twins who used cannabis more frequently than their co-twin performed worse on one working memory test (Spatial Span reversed; β = −0.07, P = 0.036). Conclusions Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests.

The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom

Abstract: Aims To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all-cause mortality (ACM) and opioid drug-related poisoning (DRP) mortality. Design Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register. Setting UK primary care. Participants A total of 11 033 opioid-dependent patients who received OST from 1998 to 2014, followed-up for 30 410 person-years. Measurements Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed-up for 16 363 person-years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine. Findings ACM and DRP rates were 1.93 and 0.53 per 100 person-years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97-3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45-12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47-3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01-0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17-0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively. Conclusions In UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all-cause and drug-related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.

Trends and age, period and cohort effects for marijuana use prevalence in the 1984-2015 US National Alcohol Surveys.

Abstract: Background and Aims Epidemiological trends show marijuana use in the U.S. to have increased in recent years. Previous research has identified cohort effects as contributing to the rising prevalence, in particular birth cohorts born after 1945. However, given recent policy efforts to regulate marijuana use at the state level, period effects could also play a contributing role. This study aims to examine whether cohort or period effects play a larger role in explaining trends in marijuana use. Design Using data from seven National Alcohol Surveys, we estimate age-period cohort decomposition models for marijuana use controlling for socio-demographic measures. Setting United States Participants U.S. general population ages 18 and older from 1984 to 2015. Measurements Any past year marijuana use Findings Results indicate that period effects are the main driver of rising marijuana use prevalence. Models including indicators of medical and recreational marijuana policies do not find any significant positive impacts. Conclusions The steep rise in marijuana use in the United States since 2005 occurred across the population and is attributable to general period effects not specifically linked to the liberalization of marijuana policies in some states.

The prevalence, incidence, and gender and age‐specific incidence of problem gambling: results of the Swedish longitudinal gambling study (Swelogs)

Abstract: AIMS To estimate the prevalence, incidence and gender and age-specific incidence of problem gambling in the Swedish adult population. DESIGN Longitudinal cohort study with linkage to register data. SETTING Sweden. PARTICIPANTS Stratified random sample aged 16-84 years at baseline (n = 8165) re-assessed a year later (n = 6021). MEASUREMENTS Problem gambling (life-time and past 12 months) was measured by the South Oaks Gambling Screen-Revised (SOGS-R). Past 12-month (current) problem gambling was also measured by the Problem Gambling Severity Index (PGSI). FINDINGS The SOGS-R combined current pathological and problem gambling prevalence rate (PR) was 2.1 [95% confidence interval (CI) = 1.8-2.4] at baseline and 1.7 (1.4-2.0) at follow-up, approximately half the corresponding life-time estimates.[Correction added on 22 Dec 2017, after first online publication: In the preceding sentence, the SOGS-R combined current pathological and problem gambling prevalence rate (PR) was incorrectly reported as being double the corresponding life-time rate. It has been corrected in this version.] PGSI combined current problem and moderate-risk gambling PRs were 2.2 (1.9-2.5) at baseline and 1.9 (1.6-2.2) at follow-up. Combined incidence rates (IRs) were 1.0 (0.8-1.3) (SOGS-R) and 1.4 (1.1-1.7) (PGSI), with more than three-quarters being new cases. While first-time IRs did not vary by gender, males had a higher relapse IR and proportionately more females were new cases. The young adult IR was more than double the older adult IR; similar proportions were new cases. CONCLUSIONS The actual incidence of problem gambling relapse in Sweden is likely to be higher than estimated. The profile of problem gambling in Sweden is likely to change over time, with increased proportions of women and older adults.

How do we determine the impact of e-cigarettes on cigarette smoking cessation or reduction? Review and recommendations for answering the research question with scientific rigor

Abstract: Aims To propose a hierarchy of methodological criteria to consider when determining whether a study provides sufficient information to answer the question of whether e-cigarettes can facilitate cigarette smoking cessation or reduction. Design A PubMed search to 1 February 2017 was conducted of all studies related to e-cigarettes and smoking cessation or reduction. Settings Australia, Europe, Iran, Korea, New Zealand and the United States. Participants and studies 91 articles. Measurements Coders organized studies according to six proposed methodological criteria: (1) examines outcome of interest (cigarette abstinence or reduction), (2) assesses e-cigarette use for cessation as exposure of interest, (3) employs appropriate control/comparison groups, (4) ensures that measurement of exposure precedes the outcome, (5) evaluates dose and duration of the exposure and (6) evaluates the type and quality of the e-cigarette used. Findings Twenty-four papers did not examine the outcomes of interest. Forty did not assess the specific reason for e-cigarette use as an exposure of interest. Twenty papers did not employ prospective study designs with appropriate comparison groups. The few observational studies meeting some of the criteria (duration, type, use for cessation) triangulated with findings from three randomized trials to suggest that e-cigarettes can help adult smokers quit or reduce cigarette smoking. Conclusions Only a small proportion of studies seeking to address the effect of e-cigarettes on smoking cessation or reduction meet a set of proposed quality standards. Those that do are consistent with randomized controlled trial evidence in suggesting that e-cigarettes can help with smoking cessation or reduction.

Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e-cigarette and a tobacco cigarette.

Abstract: Aims To measure carbonyl emissions from a heated tobacco product (IQOS) in comparison with an e-cigarette (Nautilus Mini) and a commercial tobacco cigarette (Marlboro Red). Design Regular and menthol variants of the heated tobacco product were tested. A tank-type atomizer was tested with a tobacco-flavoured liquid at 10 and 14 W. Aerosol and smoke were collected in impingers containing 2,4-dinitrophenylhydrazine. Health Canada Intense and two more intense puffing regimens were used. Setting Analytical laboratory in Greece. Measurements Carbonyl levels in the aerosol and smoke. Findings At the Health Canada Intense regimen, heated tobacco products emitted 5.0-6.4 μg/stick formaldehyde, 144.1-176.7 μg/stick acetaldehyde, 10.4-10.8 μg/stick acrolein, 11.0-12.8 μg/stick propionaldehyde and 1.9-2.0 μg/stick crotonaldehyde. Compared with the tobacco cigarette, levels were on average 91.6% lower for formaldehyde, 84.9% lower for acetaldehyde, 90.6% lower for acrolein, 89.0% lower for propionaldehyde and 95.3% lower for crotonaldehyde. The e-cigarette emitted 0.5-1.0 μg/12 puffs formaldehyde, 0.8-1.5 μg/12 puffs acetaldehyde and 0.3-0.4 μg/12 puffs acrolein, but no propionaldehyde and crotonaldehyde. At more intense puffing regimens, formaldehyde was increased in heated tobacco products, but levels were three-fourfold lower compared with the tobacco cigarette. Based on the findings from Health Canada Intense puffing regimen, use of 20 heated tobacco sticks would result in approximately 85% to 95% reduced carbonyl exposure compared with smoking 20 tobacco cigarettes; the respective reduction in exposure from use of 5 g e-cigarette liquid would be 97% to > 99%. Conclusions The IQOS heated tobacco product emits substantially lower levels of carbonyls than a commercial tobacco cigarette (Marlboro Red) but higher levels than a Nautilus Mini e-cigarette.

'Real-world' compensatory behaviour with low nicotine concentration e-liquid: subjective effects and nicotine, acrolein and formaldehyde exposure

Abstract: Aims: To compare the effects of i) high versus low nicotine concentration e-liquid, ii) fixed versus adjustable power and iii) the interaction between the two on: a) vaping behaviour, b) subjective effects, c) nicotine intake, and d) exposure to acrolein and formaldehyde in e-cigarette users vaping in their everyday setting. Design: Counterbalanced, repeated measures with four conditions: i) low nicotine (6 mg/mL)/fixed power; ii) low nicotine/adjustable power; iii) high nicotine (18 mg/mL)/fixed power; iv) high nicotine/adjustable power. Setting: London and the South East, England. Participants: Twenty experienced e-cigarette users (recruited between September 2016 and February 2017) vaped ad libitum using an eVic Supreme™ with a ‘Nautilus Aspire’ tank over four weeks (one week per condition). Measurements: Puffing patterns (daily puff number [PN], puff duration [PD], inter-puff interval [IPI]), mL of e-liquid consumed, changes to power (where permitted), and subjective effects (urge to vape, nicotine withdrawal symptoms) were measured in each condition. Nicotine intake was measured via salivary cotinine. 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of the toxicant acrolein, and formate, a metabolite of the carcinogen formaldehyde, were measured in urine. Findings: There was a significant nicotine concentration x power interaction for PD (p<0.01). PD was longer with low nicotine/fixed power compared with i) high nicotine/fixed power (p< 0.001 and ii) low nicotine/adjustable power (p< 0.01). PN and liquid consumed were higher in the low versus high nicotine condition (main effect of nicotine, p<0.05). Urge to vape and withdrawal symptoms were lower, and nicotine intake was higher, in the high nicotine condition (main effects of nicotine: p<0.01). Whilst acrolein levels did not differ, there was a significant nicotine x power interaction for formaldehyde (p<0.05). Conclusions: Use of a lower nicotine concentration e-liquid was may be associated with compensatory behaviour (e.g., higher number and duration of puffs) and increases in negative affect, urge to vape, and formaldehyde exposure.

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal

Abstract: This research was funded by a PhD Studentship from the Medical Research Council (MRC) to CH and an MRC DPFS award (MR/K015524/1) to HVCand CJAM. TPF is funded by a Senior Academic Fellowship from the Society for the Study of Addiction.

Scaling‐up HCV prevention and treatment interventions in rural United States—model projections for tackling an increasing epidemic

Abstract: Background and aims Effective strategies are needed to address dramatic increases in hepatitis C virus (HCV) infection among people who inject drugs (PWID) in rural settings of the United States. We determined the required scale-up of HCV treatment with or without scale-up of HCV prevention interventions to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025 and 2030 in a rural US setting. Design An ordinary differential equation model of HCV transmission calibrated to HCV epidemiological data obtained primarily from an HIV outbreak investigation in Indiana. Setting Scott County, Indiana (population 24 181), USA, a rural setting with negligible baseline interventions, increasing HCV epidemic since 2010, and 55.3% chronic HCV prevalence among PWID in 2015. Participants PWID. Measurements Required annual HCV treatments per 1000 PWID (and initial annual percentage of infections treated) to achieve a 90% reduction in HCV chronic prevalence or incidence by 2025/30, either with or without scaling-up syringe service programmes (SSPs) and medication-assisted treatment (MAT) to 50% coverage. Sensitivity analyses considered whether this impact could be achieved without re-treatment of re-infections, and whether greater intervention scale-up was required due to the increasing epidemic in this setting. Findings To achieve a 90% reduction in incidence and prevalence by 2030, without MAT and SSP scale-up, 159 per 1000 PWID (initially 24.9% of infected PWID) need to be HCV-treated annually. However, with MAT and SSP scaled-up, treatment rates are halved (89 per 1000 annually or 14.5%). To reach the same target by 2025 with MAT and SSP scaled-up, 121 per 1000 PWID (19.9%) need treatment annually. These treatment requirements are threefold higher than if the epidemic was stable, and the impact targets are unattainable without retreatment. Conclusions Combined scale-up of hepatitis C virus treatment and prevention interventions is needed to decrease the increasing burden of hepatitis C virus incidence and prevalence in rural Indiana, USA, by 90% by 2025/30.

A systematic review of the next-day effects of heavy alcohol consumption on cognitive performance.

Abstract: BACKGROUND AND AIMS Studies examining the next-day cognitive effects of heavy alcohol consumption have produced mixed findings, which may reflect inconsistencies in definitions of 'hangover'. Recent consensus has defined hangover as 'mental and physical symptoms, experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration (BAC) approaches zero'. In light of this, we aimed to review the literature systematically to evaluate and estimate mean effect sizes of the next-day effects of heavy alcohol consumption on cognition. METHODS Embase, PubMed and PsycNET databases were searched between December 2016 and May 2018 using terms based on 'alcohol' and 'hangover'. Studies of experimental designs which reported the next-day cognitive effects of heavy alcohol consumption in a 'hangover' group with BAC < 0.02% were reviewed. A total of 805 articles were identified. Thirty-nine full-text articles were screened by two independent reviewers and 19 included in the systematic review; 11 articles provided sufficient data to be included in the meta-analysis; 1163 participants across 19 studies conducted since 1970 were included in the analysis. Data for study design, hangover severity, BAC at testing and cognitive performance were extracted and effect estimates calculated. RESULTS The systematic review suggested that sustained attention and driving abilities were impaired during hangover. Mixed results were observed for: psychomotor skills, short- (STM) and long-term memory (LTM) and divided attention. The meta-analysis revealed evidence of impairments in STM [g = 0.64, 95% confidence interval (CI) = 0.15-1.13], LTM (Hedges' g = 0.59, 95% CI = 0.01-1.17) sustained attention (g = 0.47, 95% CI = 0.07-0.87) and psychomotor speed (Hedges' g = 0.66, 95% CI = 0.31-1.00) during alcohol hangover. CONCLUSION The research literature suggests that alcohol hangovers may involve impaired cognitive functions and performance of everyday tasks such as driving.

Improving quit rates of web-delivered interventions for smoking cessation: full-scale randomized trial of WebQuit.org versus Smokefree.gov.

Abstract: Background and aims Millions of people world-wide use websites to help them quit smoking, but effectiveness trials have an average 34% follow-up data retention rate and an average 9% quit rate. We compared the quit rates of a website using a new behavioral approach called Acceptance and Commitment Therapy (ACT; WebQuit.org) with the current standard of the National Cancer Institute's (NCI) Smokefree.gov website. Design A two-arm stratified double-blind individually randomized trial (n = 1319 for WebQuit; n = 1318 for Smokefree.gov) with 12-month follow-up. Setting United States. Participants Adults (n = 2637) who currently smoked at least five cigarettes per day were recruited from March 2014 to August 2015. At baseline, participants were mean [standard deviation (SD)] age 46.2 years (13.4), 79% women and 73% white. Interventions WebQuit.org website (experimental) provided ACT for smoking cessation; Smokefree.gov website (comparison) followed US Clinical Practice Guidelines for smoking cessation. Measurements The primary outcome was self-reported 30-day point prevalence abstinence at 12 months. Findings The 12-month follow-up data retention rate was 88% (2309 of 2637). The 30-day point prevalence abstinence rates at the 12-month follow-up were 24% (278 of 1141) for WebQuit.org and 26% (305 of 1168) for Smokefree.gov [odds ratio (OR) = 0.91; 95% confidence interval (CI) = 0.76, 1.10; P = 0.334] in the a priori complete case analysis. Abstinence rates were 21% (278 of 1319) for WebQuit.org and 23% (305 of 1318) for Smokefree.gov (OR = 0.89 (0.74, 1.07; P = 0.200) when missing cases were imputed as smokers. The Bayes factor comparing the primary abstinence outcome was 0.17, indicating 'substantial' evidence of no difference between groups. Conclusions WebQuit.org and Smokefree.gov had similar 30-day point prevalence abstinence rates at 12 months that were descriptively higher than those of prior published website-delivered interventions and telephone counselor-delivered interventions.

Direct‐acting antiviral treatment of chronic HCV‐infected patients on opioid substitution therapy: Still a concern in clinical practice?

Abstract: BACKGROUND AND AIMS There is limited real-world information on the effectiveness of antiviral treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAA) in people on opioid substitution therapy (OST). This study compared sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST and non-OST patients in the German Hepatitis C-Registry (DHC-R). DESIGN National multi-centre prospective real-world registry (German Hepatitis C-Registry, DHC-R). Non-OST patients comprised patients with former/current drug use (non-OST/DU) and patients never consuming drugs (non-OST/NDU). SETTING A total of 254 medical centres in Germany, including 123 centres providing OST. PARTICIPANTS A total of 7747 chronic HCV patients started DAA therapy (739 OST and 7008 non-OST; 1500 non-OST/DU; 5508 non-OST/NDU) patients. Five hundred and twenty-eight OST and 5582 non-OST patients had completed antiviral therapy and at least one follow-up documentation [intention-to-treat (ITT) population]. MEASUREMENTS Study outcomes were SVR, proportion of LTFU and safety of treatment. FINDINGS SVR (ITT) was documented in 85% (450 of 528) OST patients versus 86% (969 of 1126) in non-OST/DU (P = 0.651) and 92% (4113 of 4456) non-OST/NDU (P 90 × 109/l (aOR = 1.51, CI = 1.14-2.01), cirrhosis (aOR = 0.77; CI = 0.62-0.96) and patient group (OST/DI (aOR = 0.58; CI = 0.42-0.78); non-OST/DU (OR: 0.63; CI = 0.50-0.78). In per-protocol analysis (PP), SVR rates were ≥ 94% in all patient groups. In OST the proportion of LTFU was higher (10.2%) than in non-OST/DU (8.5%) and non-OST/NDU (3.2%, P < 0.001) patients. Independent factors for LTFU (P < 0.01) were HCV genotype non-3 (aOR = 0.92; CI = 0.88-0.96), female sex (aOR: 0.7; CI = 0.53-0.92), pre-treatment (aOR = 0.64; CI = 0.50-0.82), OST/DI (aOR = 3.35; CI = 2.35-4.78) and non-OST/DU (aOR = 2.38; CI = 1.80-3.14). CONCLUSIONS In Germany, direct-acting antiviral treatment of former or current drug users with or without opioid substitution therapy can achieve equally high sustained virological response rates as in patients with no history of drug use.

Qualitative research: Qualitative research

Abstract: BACKGROUND AND AIMS This narrative review aims to highlight key insights from qualitative research on drug use and drug users by profiling a selection of classic works. METHODS Consensus methods were used to identify and select four papers published in 1938, 1969, 1973 and 1984 considered to be classics. RESULTS These landmark qualitative studies included the first account of addiction as a social process, demonstrating that people have meaningful responses to drug use that cannot be reduced to their pharmacological effects; the portrayal of inner-city heroin users as exacting, energetic and engaged social agents; identification of the interactive social learning processes involved in becoming a drug user; the application of the 'career' concept to understanding transitions and trajectories of drug use over time; and the articulation of a framework for understanding drug use that incorporates the interaction between pharmacology, psychology and social environments. CONCLUSIONS These classic sociological and anthropological studies deployed qualitative research methods to show how drug use is shaped by complex sets of factors situated within social contexts, viewing drug users as agents engaged actively in social processes and worlds. Their findings have been used to challenge stereotypes about drug use and drug users, develop a deeper understanding of drug use among hidden, hard-to-research and under-studied populations, and provide the foundations for significant developments in scientific knowledge about the nature of drug use. They continue to retain their relevance, providing important correctives to biomedical and behaviourist paradigms, reminding us that drug use is a social process, and demonstrating how the inductive approach of qualitative research can strengthen the way we understand and respond to drug use and related harms.

Efficacy of a web-based intervention with and without guidance for employees with risky drinking : results of a three-arm randomized controlled trial

Abstract: AIMS: To test the efficacy of a web-based alcohol intervention with and without guidance. DESIGN: Three parallel groups with primary end-point after 6 weeks. SETTING: Open recruitment in the German working population. PARTICIPANTS: Adults (178 males/256 females, mean age 47 years) consuming at least 21/14 weekly standard units of alcohol (SUA) and scoring ≥ 8/6 on the Alcohol Use Disorders Identification Test. INTERVENTION: Five web-based modules including personalized normative feedback, motivational interviewing, goal setting, problem-solving and emotion regulation during 5 weeks. One intervention group received an unguided self-help version (n=146) and the second received additional adherence-focused guidance by eCoaches (n=144). Controls were on a waiting list with full access to usual care (n=144). MEASUREMENTS: Primary outcome was weekly consumed SUA after 6 weeks. SUA after 6 months was examined as secondary outcome, next to numbers of participants drinking within the low-risk range, and general and work-specific mental health measures. FINDINGS: All groups showed reductions of mean weekly SUA after 6 weeks (unguided: -8.0; guided: -8.5; control: -3.2). There was no significant difference between the unguided and guided intervention (P=0.324). Participants in the combined intervention group reported significantly fewer SUA than controls [B=-4.85, 95% confidence interval (CI)=-7.02 to -2.68, P < 0.001]. The intervention groups also showed significant reductions in SUA consumption after 6 months (B=-5.72, 95% CI=-7.71 to -3.73, P < 0.001) and improvements regarding general and work-related mental health outcomes after 6 weeks and 6 months. CONCLUSIONS: A web-based alcohol intervention, administered with or without personal guidance, significantly reduced mean weekly alcohol consumption and improved mental health and work-related outcomes in the German working population.

Medical cannabis legalization and opioid prescriptions: evidence on US Medicaid enrollees during 1993–2014

Abstract: Background and aims While the United States has been experiencing an opioid epidemic, 29 states and Washington DC have legalized cannabis for medical use. This study examined whether state-wide medical cannabis legalization was associated with reduction in opioids received by Medicaid enrollees. Design Secondary data analysis of state-level opioid prescription records from 1993-2014 Medicaid State Drug Utilization Data. Linear time-series regressions assessed the associations between medical cannabis legalization and opioid prescriptions, controlling for state-level time-varying policy covariates (such as prescription drug monitoring programs) and socio-economic covariates (such as income). Setting United States. Participants Drug prescription records for patients enrolled in fee-for-service Medicaid programs that primarily provide health-care coverage to low-income and disabled people. Measurements The primary outcomes were population-adjusted number, dosage and Medicaid spending on opioid prescriptions. Outcomes for Schedule II opioids (e.g. hydrocodone, oxycodone) and Schedule III opioids (e.g. codeine) were analyzed separately. The primary policy variable of interest was the implementation of state-wide medical cannabis legalization. Findings For Schedule III opioid prescriptions, medical cannabis legalization was associated with a 29.6% (P = 0.03) reduction in number of prescriptions, 29.9% (P = 0.02) reduction in dosage and 28.8% (P = 0.04) reduction in related Medicaid spending. No evidence was found to support the associations between medical cannabis legalization and Schedule II opioid prescriptions. Permitting medical cannabis dispensaries was not associated with Schedule II or Schedule III opioid prescriptions after controlling for medical cannabis legalization. It was estimated that, if all the states had legalized medical cannabis by 2014, Medicaid annual spending on opioid prescriptions would be reduced by 17.8 million dollars. Conclusion State-wide medical cannabis legalization appears to have been associated with reductions in both prescriptions and dosages of Schedule III (but not Schedule II) opioids received by Medicaid enrollees in the United States.