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Background: Stimulant-related overdoses have increased dramatically, with almost 50% of overdoses in the United States now involving stimulants. Additionally, harm-reduction approaches are increasingly seen as key to reducing the negative impact of substance use. Contingency management (CM), the provision of financial incentives for abstinence, is the most effective treatment for stimulant use disorder, but historically has not been widely implemented. Many recent, large-scale implementation efforts have relied upon foundational CM protocols that may not sufficiently account for recent increases in the prevalence and lethality of stimulant use nor the growing preference for harm reduction versus abstinence-only frameworks., Argument: We argue the need to (1) consider whether and how CM protocols might be modified to address rising stimulant use and harm reduction frameworks and (2) make CM widely accessible so that it can reduce population-level stimulant use while ensuring that it is delivered with fidelity to its basic principles. Proposed changes include changing CM reinforcement schedules to emphasize treatment engagement and reductions in use in addition to abstinence, changing guidelines on the duration of and re-engagement in CM, investing in research on virtual CM, incentivizing providers and health systems to deliver CM, making it easier to purchase and use point-of-care drug screens, using direct-to-consumer marketing to increase demand for CM and adapting CM to the community in which it is being implemented., Conclusions: Our proposed modifications to contingency management (CM) protocols and accessibility may more effectively address rising stimulant use and align CM more closely with harm-reduction frameworks. Given the urgent need to reduce overdose deaths, developing and testing modified CM protocols may need to rely upon methods other than randomized controlled trials. Efforts to disseminate CM widely to reduce population-level stimulant use must be balanced with the need to maintain fidelity to CM's basic principles., (© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background and Aims: Solitary drug use (SDU) can amplify risks of fatal overdose. We examined competing risks and drivers of SDU, as well as harm reduction strategies implemented during SDU episodes, among women who inject drugs (WWID)., Design: A cross-sectional qualitative study, including telephone and face-to-face in-depth interviews., Setting: Baltimore City, MD, USA., Participants: Twenty-seven WWID (mean age = 39 years, 67% white, 74% injected drugs daily) recruited via outreach and street intercept (April-September 2021)., Measurements: Interviews explored the physical (i.e. indoor/private, outdoor/public) and social (i.e. alone, accompanied) risk environments in which drug use occurred. Guided by the principles of emergent design, we used thematic analysis to interrogate textual data, illuminating women's preferences/motivations for SDU and strategies for minimizing overdose risks when using alone., Findings: Many participants reported experiences with SDU, despite expressed preferences for accompanied drug use. SDU motivations clustered around three primary drivers: (1) avoiding opioid withdrawal, (2) preferences for privacy when using drugs and (3) safety concerns, including threats of violence. Participants nevertheless acknowledged the dangers of SDU and, at times, took steps to mitigate overdose risk, including naloxone possession, communicating to peers when using alone ('spotting') and using drugs in public spaces., Conclusions: WWID appear to engage frequently in SDU due to constraints of the physical and social environments in which they use drugs. They express a preference for accompanied drug use in most cases and report implementing strategies to mitigate their overdose risk, especially when using drugs alone., (© 2022 Society for the Study of Addiction.)

Background and Aims: Medications for opioid use disorder (MOUD) are shown to reduce opioid use and the risk of overdose. People with opioid use disorder (OUD) who exit inpatient medically managed withdrawal programs (detox) without initiating MOUD and linking to outpatient care have high rates of overdose. While detox encounters provide a theoretical opportunity for MOUD initiation, this is not ubiquitous in the United States. We used simulation modeling to estimate the population-level health effects and cost-effectiveness of a policy encouraging MOUD initiation during inpatient detox encounters., Design, Setting and Participants: We employed a dynamic population state-transition model to evaluate the effectiveness and cost-effectiveness of using detox programs as venues for initiating MOUD in Massachusetts, United States. We compared standard of care, where no detox patients initiate MOUD or link to outpatient MOUD providers, to strategies of offering MOUD to detox patients and linking those patients to outpatient MOUD., Measures: Budgetary impact to the Massachusetts health-care sector, incremental cost-effectiveness ratios (ICER) and total counts and percentage differences of fatal overdoses prevented., Findings: Initiating MOUD in detox with perfect linkage to outpatient MOUD would reduce fatal overdoses by 4.5% [95% confidence interval (CI) = 2.3-5.9], at an ICER of $56 000 per quality-adjusted life-year (QALY) gained, compared with the standard of care. With moderate linkage, fatal overdoses would be reduced by 2.3% (95% CI= 1.2-3.1) with an ICER of $78 500 per QALY gained, compared with standard of care. Budgetary increase to Massachusetts health-care spending ranged from 0.5-1%., Conclusion: A simulation model indicates that initiation of medications for opioid use disorder and linkage policies among detox patients in Massachusetts, USA could prevent fatal opioid overdoses in the opioid use disorder population and would be cost-effective from a health-care sector perspective., (© 2022 Society for the Study of Addiction.)

Background and Aims: Opioid-related overdose death rates continue to rise in the United States, especially in racial/ethnic minority communities. Our objective was to determine if US municipalities with high percentages of non-white residents have equitable access to the overdose antidote naloxone distributed by community-based organizations., Methods: We used community-based naloxone data from the Massachusetts Department of Public Health and the Rhode Island non-pharmacy naloxone distribution program for 2016-18. We obtained publicly available opioid-related overdose death data from Massachusetts and the Office of the State Medical Examiners in Rhode Island. We defined the naloxone coverage ratio as the number of community-based naloxone kits received by a resident in a municipality divided by the number of opioid-related overdose deaths among residents, updated annually. We used a Poisson regression with generalized estimating equations to analyze the relationship between the municipal racial/ethnic composition and naloxone coverage ratio. To account for the potential non-linear relationship between naloxone coverage ratio and race/ethnicity we created B-splines for the percentage of non-white residents; and for a secondary analysis examining the percentage of African American/black and Hispanic residents. The models were adjusted for the percentage of residents in poverty, urbanicity, state and population size., Results: Between 2016 and 2018, the annual naloxone coverage ratios range was 0-135. There was no difference in naloxone coverage ratios among municipalities with varying percentages of non-white residents in our multivariable analysis. In the secondary analysis, municipalities with higher percentages of African American/black residents had higher naloxone coverage ratios, independent of other factors. Naloxone coverage did not differ by percentage of Hispanic residents., Conclusions: There appear to be no municipal-level racial/ethnic inequities in naloxone distribution in Rhode Island and Massachusetts, USA., (© 2021 Society for the Study of Addiction.)

Background and Aims: Although most opioid-related mortality in Australia involves prescription opioids, most research to understand the impact of naloxone supply on opioid-related mortality has focused upon people who inject heroin. We aimed to examine the cost and probable impact of up-scaling naloxone supply to people who are prescribed opioids., Design: Decision-tree model. Four scenarios were compared with a baseline scenario (the current status quo): naloxone scale-up between 2020 and 2030 to reach 30 or 90% coverage by 2030, among the subgroups of people prescribed either ≥ 50 or ≥ 100 mg of oral morphine equivalents (OME)., Setting: Australia., Participants: People who are prescribed opioids., Measurements: Possible deaths averted, costs (ambulance and naloxone distribution) and cost per life saved for different scenarios of naloxone scale-up., Findings: Maintaining the status quo, there would be an estimated 7478 [uncertainty interval (UI) = 6868-8275] prescription opioid overdose deaths between 2020 and 2030, resulting in Australian dollars (A$)51.9 million (49.4, 56.0) in ambulance costs. If naloxone were scaled-up to 90% of people prescribed > 50 mg OME, an estimated 657 (UI = 245, 1489) deaths could be averted between 2020 and 2030 (a 20% reduction in the final year of the model compared with the no naloxone scenario), with a cost of A$43 600 (20 800-110 500) per life saved. If naloxone were scaled-up to 30% of people prescribed > 50 mg OME an estimated 219 (82-496) deaths could be averted with the same cost per live saved. If naloxone were restricted to those prescribed > 100 mg OME, an estimated 130 (UI = 44-289) deaths would be averted if scaled-up to 30% or 390 (UI = 131-866) deaths averted if scaled-up to 90%, with the cost per life saved for both scenarios A$38 200 (UI = 12 400-97 400)., Conclusion: In Australia, scaling-up take-home naloxone by 2030 to reach 90% of people prescribed daily doses of ≥ 50 mg of oral morphine equivalents would be cost-effective and save more than 650 lives., (© 2021 Society for the Study of Addiction.)

Background and Aims: In light of the accelerating drug overdose epidemic in North America, new strategies are needed to identify communities most at risk to prioritize geographically the existing public health resources (e.g. street outreach, naloxone distribution efforts). We aimed to develop PROVIDENT (Preventing Overdose using Information and Data from the Environment), a machine learning-based forecasting tool to predict future overdose deaths at the census block group (i.e. neighbourhood) level., Design: Randomized, population-based, community intervention trial., Setting: Rhode Island, USA., Participants: All people who reside in Rhode Island during the study period may contribute data to either the model or the trial outcomes., Intervention: Each of the state's 39 municipalities will be randomized to the intervention (PROVIDENT) or comparator condition. An interactive, web-based tool will be developed to visualize the PROVIDENT model predictions. Municipalities assigned to the treatment arm will receive neighbourhood risk predictions from the PROVIDENT model, and state agencies and community-based organizations will direct resources to neighbourhoods identified as high risk. Municipalities assigned to the control arm will continue to receive surveillance information and overdose prevention resources, but they will not receive neighbourhood risk predictions., Measurements: The primary outcome is the municipal-level rate of fatal and non-fatal drug overdoses. Fatal overdoses will be defined as unintentional drug-related death; non-fatal overdoses will be defined as an emergency department visit for a suspected overdose reported through the state's syndromic surveillance system. Intervention efficacy will be assessed using Poisson or negative binomial regression to estimate incidence rate ratios comparing fatal and non-fatal overdose rates in treatment vs. control municipalities., Comments: The findings will inform the utility of predictive modelling as a tool to improve public health decision-making and inform resource allocation to communities that should be prioritized for prevention, treatment, recovery and overdose rescue services., (© 2021 Society for the Study of Addiction.)

Aims: To explore how people who use fentanyl and health-care providers engaged in and responded to overdose risk communication interactions, and how these engagements and responses might vary by age., Design: A single-site qualitative in-depth interview study., Setting: Boston, MA, United States., Participants: The sample included 21 people (10 women, 11 men) who were either 18-25 or 35+, English-speaking, and reported illicit fentanyl use in the last year and 10 health-care providers who worked directly with people who use fentanyl (PWUF) in clinical and community settings., Measurements: Open-ended, flexible interview questions guided by a risk communication framework were used in all interviews. Codes used for thematic analysis included deductive codes related to the risk communication framework and inductive, emergent codes from interview content., Findings: We identified potential age-based differences in perceptions of fentanyl overdose, including that younger participants appeared to display more perceptions of an immunity to fentanyl's lethality, while older people seemed to express a stronger aversion to fentanyl due to its heightened risk of fatal overdose, shorter effects and potential for long-term health consequences. Providers perceived greater challenges relaying risk information to young PWUF and believed them to be less open to risk communication. Compassionate harm reduction communication was preferred by all participants and perceived to be delivered most effectively by community health workers and peers. PWUF and providers identified structural barriers that limited compassionate harm reduction, including misalignment of available treatment with preferred options and clinical structures that impeded the delivery of risk communication messages., Conclusions: Among people who engage in illicit fentanyl use, fentanyl-related risk communication experiences and preferences may vary by age, but some foundational elements including compassionate, trust-building approaches seem to be preferred across the age spectrum. Structural barriers in the clinical setting such as provider-prescribing power and infrequent encounters may impede the providers' ability to provide compassionate harm reduction communication., (© 2020 Society for the Study of Addiction.)

Background: Overdose deaths related to illegal drugs in North American markets are now dominated by potent synthetic opioids such as fentanyl, a circumstance foreshadowed by often-overlooked events in Estonia since the turn of the century. Market transitions generate important and far-reaching implications for drug policy., Argument and Analysis: The supplier-driven introduction of illegally manufactured synthetic opioids into street opioids is elevating the risk of fatal overdose. Using the most recent overdose mortality and drug seizure data in North America, we find that overdose deaths and seizures involving synthetic opioids are geographically concentrated, but this might be changing. Examination here suggests that in some places fentanyl and its analogues have virtually displaced traditional opioids, such as heroin. The concealing of synthetic opioids in powders sold as heroin or pressed into counterfeit medications substantially increases harms. The nature and scale of the challenge posed by synthetic opioids is unprecedented in recent drug policy history., Conclusions: There is urgent need for policy and technological innovation to meet the challenges posed by illegally produced synthetic opioids. Novel interventions worth examining include supervising drug use, proactively deterring on-line distribution and new technologies aimed at improving transparency, such as point-of-use drug content testing. Continuing to approach this problem only with existing policies and available methods, such as naloxone, is unlikely to be enough and will result in many premature deaths., (© 2020 Society for the Study of Addiction.)

Background and Aims: Criminal justice-involved individuals carry a disproportionately higher burden of opioid use disorder (OUD) than those not involved with the criminal justice system, and are often unable to access opioid agonist therapies such as methadone and buprenorphine. The opioid receptor antagonist naltrexone (NTX) is effective for the prevention of relapse to OUD and may be more acceptable in criminal justice settings. The objectives of this review were to: (1) provide an overall summary effect across studies for the efficacy and acceptability of oral and injectable NTX for the treatment of OUD among criminal justice-involved individuals and (2) examine systematic variations in study results to explain heterogeneity among study-specific effects., Methods: Systematic review and meta-analysis of 1045 patients across 11 studies (10 randomized controlled trials, one quasi-experimental study). All available outcomes were pooled using random-effects meta-analysis. Subgroup analyses were conducted for oral and injectable naltrexone; meta-regression analyses were conducted for socio-demographic and study-level characteristics., Results: NTX improved retention in treatment [risk ratio (RR) = 1.31; 95% confidence interval (CI) = 1.05, 1.63], reduced rates of re-incarceration (RR = 0.70, 95% CI = 0.54-0.92), reduced opioid relapse (RR = 0.63, 95% CI = 0.53-0.76) and improved opioid abstinence (RR = 1.38, 95% CI = 1.16-1.65). While NTX was associated with a greater burden of adverse events overall (RR = 1.49, 95% CI = 1.13-1.95), the findings were inconclusive as to whether or not a difference was present for the number of serious adverse events or overdoses., Conclusions: Naltrexone appears to be efficacious and acceptable for the treatment of opioid use disorder among criminal justice-involved individuals; however, the risk for adverse events must be weighed against the potential benefits., (© 2019 Society for the Study of Addiction.)

Background and Aims: The province of British Columbia (BC) Canada has experienced a rapid increase in illicit drug overdoses and deaths during the last 4 years, with a provincial emergency declared in April 2016. These deaths have been driven primarily by the introduction of synthetic opioids into the illicit opioid supply. This study aimed to measure the combined impact of large-scale opioid overdose interventions implemented in BC between April 2016 and December 2017 on the number of deaths averted., Design: We expanded on the mathematical modelling methodology of our previous study to construct a Bayesian hierarchical latent Markov process model to estimate monthly overdose and overdose-death risk, along with the impact of interventions., Setting and Cases: Overdose events and overdose-related deaths in BC from January 2012 to December 2017., Interventions: The interventions considered were take-home naloxone kits, overdose prevention/supervised consumption sites and opioid agonist therapy MEASUREMENTS: Counterfactual simulations were performed with the fitted model to estimate the number of death events averted for each intervention and in combination., Findings: Between April 2016 and December 2017, BC observed 2177 overdose deaths (77% fentanyl-detected). During the same period, an estimated 3030 (2900-3240) death events were averted by all interventions combined. In isolation, 1580 (1480-1740) were averted by take-home naloxone, 230 (160-350) by overdose prevention services and 590 (510-720) were averted by opioid agonist therapy., Conclusions: A combined intervention approach has been effective in averting overdose deaths during British Columbia's opioid overdose crisis in the period since declaration of a public health emergency (April 2016-December 2017). However, the absolute numbers of overdose deaths have not changed., (© 2019 Society for the Study of Addiction.)

A rise in addiction and overdose deaths involving opioids in the United States has spurred a series of initiatives focused on reducing opioid risks, including several related to prescription of opioids in care of pain. Policy analytical scholarship provides a conceptual framework to assist in understanding this response. Prior to 2011, a 'policy monopoly' of regulators and pharmaceutical manufacturers allowed and encouraged high levels of opioid prescribing. This permissive policy fell apart in the face of adverse outcomes brought to public attention by an 'advocacy coalition' consisting of officials, thought leaders, journalists and interest groups who shared common beliefs. This coalition has generated a more cautious prescribing regimen that has incentivized involuntary termination of opioids in otherwise stable patients, with resultant reports of harm. Its emphasis on dose reduction, regardless of outcomes, mirrors in some ways the prior focus on minimizing pain scores, regardless of outcomes. Central to the present analysis is that policies cannot be comprehensively rational; rather, they emerge from a range of actors and agencies constrained in their ability to assimilate complex data, evaluate the data objectively and to command necessary resources in an iterative, rapid response fashion. The imbalance between strong prescription control and weak pain and addiction treatment expansion exemplifies the policy scholar's notion of 'bounded rationality'. Results have been suboptimum: opioid prescriptions have fallen, but harms to pain patients and overdose deaths have risen. US policymakers could revise the course through a more thoroughgoing engagement with patients, families and communities now coping with both pain and addiction., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

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., (© 2018 Society for the Study of Addiction.)

Background and Aims: In the United States, overdose deaths attributed to opioid pain relievers (OPR) have quadrupled since 1999, prompting many states to adopt Prescription Drug Monitoring Programs (PMP). This study aimed to: (1) estimate the relationship of PMP strength with OPR overdose deaths across states and over time; (2) measure what threshold in PMP strength is associated with the greatest reduction in OPR overdose; and (3) assess the relationship of medical marijuana dispensaries with OPR overdose deaths., Design: Panel data from the Centers for Disease Control and Prevention's (CDC's) Wide-ranging Online Data for Epidemiologic Research database (WONDER) were analyzed using fixed effects to regress state-year death rates on an index variable compiled from the Prescription Drug Abuse Policy System (PDAPS) while controlling for PMP administration, demographic factors and laws that might affect OPR overdose., Setting and Participants: Age-adjusted opioid overdose death rates for all 50 states and the District of Columbia between 1999 and 2014 for a total of 816 observations., Measurements: PMP strength was calculated using legal data compiled by the Prescription Drug Abuse Policy System (PDAPS). In addition to demographic controls, other covariates included laws that regulate pain clinics, access to naloxone, use of emergency services (Good Samaritan Laws) and medical marijuana., Findings: PMP strength was associated negatively with OPR overdose deaths. Every 1-point increase in PMP strength was associated with a 1% [95% confidence interval (CI) = 0.2-2%] reduction in overdose deaths. When collapsed into quartiles, PMPs in the third quartile were associated with an approximately 18% (95% CI = 1.6-29%) reduction in OPR overdose death rates compared with states without a PMP. States with medical marijuana dispensaries reported a 16% (95% CI = 1-30%) reduction in OPR overdoses., Conclusions: US states that have more robust prescription drug monitoring programs have fewer prescription opioid overdose deaths than states with weaker PMPs. States with medical marijuana dispensaries also report fewer opioid overdose deaths than states without these., (© 2016 Society for the Study of Addiction.)

Background and Aims: Lack of non-injectable naloxone formulations has impeded widespread take-home provision for the prevention of heroin/opioid overdose deaths. For non-injectable formulations that are finally being investigated, rapid onset of action and sufficient bioavailability will be vital. We present analysis of data from a study of concentrated naloxone nasal spray formulations. Our aims are: to assess (1) pharmacokinetic properties and (2) suitability for overdose reversal in terms of naloxone absorption within 30 minutes post-dosing., Design and Interventions/comparator: Open-label, randomized, four-way cross-over Latin-square pharmacokinetic study of naloxone administration by three routes: intranasal at two doses (8 mg/0.4 ml, 16 mg/0.4 ml) versus sublingual (16 mg/ml) versus intravenous reference (1 mg/ml)., Setting: Clinical Pharmacology Unit at The Ohio State University (Columbus, OH, USA)., Participants: Twelve healthy volunteers (age 20-41; seven female)., Measurements: From blood plasma naloxone concentrations, (1) standard pharmacokinetic parameters, including maximum plasma concentration (C max ) and mean absolute bioavailability (F%, relative to intravenous injection), were determined; as well as (2) partial area under the curve (AUC) values, t max (time to maximum plasma concentration) and t 50% (time to 50% of maximum plasma concentration) as measures of early absorption., Findings: (1) Bioavailability was F% = 25-28% for intranasal naloxone. Sublingual had low bioavailability (F% = 2%) and was not considered further. Mean C max values for 8 mg (12.83 ng/ml) and 16 mg (18.25 ng/ml) intranasal exceeded 1 mg intravenous (9.64 ng/ml) naloxone. (2) Following intranasal administration, t 50% was reached within 8 minutes and t max within 20 minutes. Mean naloxone absorption from dosing to 30 minutes (AUC 30 ) was greater following 8 mg (4.17 h × ng/ml) and 16 mg (5.91 h × ng/ml) intranasal than following 1 mg intravenous (1.70 h × ng/ml) administration., Conclusions: Concentrated naloxone nasal spray has a promising pharmacokinetic profile, with substantial bioavailability. Its early absorption time-course suggests that concentrated nasal naloxone is suitable for emergency administration in the community, where rapid restoration of respiratory function is essential for opioid overdose reversal., (© 2017 Society for the Study of Addiction.)

Background and Aims: People with opioid use disorder (OUD) in prison face an acute risk of death after release. We estimated whether prison-based opioid substitution treatment (OST) reduces this risk., Design: Prospective observational cohort study using prison health care, national community drug misuse treatment and deaths registers., Setting: Recruitment at 39 adult prisons in England (32 male; seven female) accounting for 95% of OST treatment in England during study planning., Participants: Adult prisoners diagnosed with OUD (recruited: September 2010-August 2013; first release: September 2010; last release: October 2014; follow-up to February 2016; n = 15 141 in the risk set)., Intervention and Comparator: At release, participants were classified as OST exposed (n = 8645) or OST unexposed (n = 6496). The OST unexposed group did not receive OST, or had been withdrawn, or had a low dose., Measurements: Primary outcome: all-cause mortality (ACM) in the first 4 weeks., Secondary Outcomes: drug-related poisoning (DRP) deaths in the first 4 weeks; ACM and DRP mortality after 4 weeks to 1 year; admission to community drug misuse treatment in the first 4 weeks. Unadjusted and adjusted Cox regression models (covariates: sex, age, drug injecting, problem alcohol use, use of benzodiazepines, cocaine, prison transfer and admission to community treatment), tested difference in mortality rates and community treatment uptake., Findings: During the first 4 weeks after prison release there were 24 ACM deaths: six in the OST exposed group and 18 in the OST unexposed group [mortality rate 0.93 per 100 person-years (py) versus 3.67 per 100 py; hazard ratio (HR) = 0.25; 95% confidence interval (CI) = 0.10-0.64]. There were 18 DRP deaths: OST exposed group mortality rate 0.47 per 100 py versus 3.06 per 100 py in the OST unexposed group (HR = 0.15; 95% CI = 0.04-0.53). There was no group difference in mortality risk after the first month. The OST exposed group was more likely to enter drug misuse treatment in the first month post-release (odds ratio 2.47, 95% CI = 2.31-2.65). The OST mortality protective effect on ACM and DRP mortality risk was not attenuated by demographic, overdose risk factors, prison transfer or community treatment (fully adjusted HR = 0.25; 95% CI = 0.09-0.64 and HR = 0.15; 95% CI = 0.04-0.52, respectively)., Conclusions: In an English national study, prison-based opioid substitution therapy was associated with a 75% reduction in all-cause mortality and an 85% reduction in fatal drug-related poisoning in the first month after release., (© 2017 Society for the Study of Addiction.)

Background and Aims: Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin injection have a high risk of drug-related death soon after release from prison. The NALoxone InVEstigation (N-ALIVE) pilot trial (ISRCTN34044390) tested feasibility measures for randomized provision of naloxone-on-release (NOR) to eligible prisoners in England., Design: Parallel-group randomized controlled pilot trial., Setting: English prisons., Participants: A total of 1685 adult heroin injectors, incarcerated for at least 7 days pre-randomization, release due within 3 months and more than 6 months since previous N-ALIVE release., Intervention: Using 1 : 1 minimization, prisoners were randomized to receive on release a pack containing either a single 'rescue' injection of naloxone or a control pack with no syringe., Measurements: Key feasibility outcomes were tested against prior expectations: on participation (14 English prisons; 2800 prisoners), consent (75% for randomization), returned prisoner self-questionnaires (RPSQs: 207), NOR-carriage (75% in first 4 weeks) and overdose presence (80%)., Findings: Prisons (16) and prisoners (1685) were willing to participate [consent rate, 95% confidence interval (CI) = 70-74%]; 218 RPSQs were received; NOR-carriage (95% CI = 63-79%) and overdose presence (95% CI = 75-84%) were as expected. We randomized 842 to NOR and 843 to control during 30 months but stopped early, because only one-third of NOR administrations were to the ex-prisoner. Nine deaths within 12 weeks of release were registered for 1557 randomized participants released before 9 December 2014., Conclusions: Large randomized trials are feasible with prison populations. Provision of take-home emergency naloxone prior to prison release may be a life-saving interim measure to prevent heroin overdose deaths among ex-prisoners and the wider population., (© 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background and Aims: The time available to act is a crucial factor affecting the probable success of interventions to manage opiate overdose. We analyse opiate users' accounts of non-fatal overdose incidents to (i) construct a proto-typology of non-fatal opiate overdose onset and (ii) assess the implications for overdose management and prevention of fatalities., Methods: Re-analysis of a subset of data from a large qualitative study of non-fatal opiate overdose conducted from 1997 to 1999. Data were generated from semi-structured interviews undertaken with opiate users who had experienced a non-fatal overdose in the previous 24 hours. Forty-four participants (30 men; 14 women; aged 16-47 years) provided sufficient information for in-depth analysis. Data relating to 'memory of the moment of overdose', 'time to loss of consciousness' and 'subjective description of the overdose experience' were scrutinised using iterative categorization., Findings: Four types of overdose onset were identified: type A 'amnesic' (n = 8), characterized by no memory, rapid loss of consciousness and no description of the overdose experience; type B 'conscious' (n = 17), characterized by some memory, sustained consciousness and a description of the overdose in terms of feeling unwell and symptomatic; type C 'instant' (n = 14), characterized by some memory, immediate loss of consciousness and no description of the overdose experience; and type D 'enjoyable' (n = 5), characterized by some memory, rapid loss of consciousness and a description of the overdose experience as pleasant or positive., Conclusions: The identification of different types of overdose onset highlights the complexity of overdose events, the need for a range of interventions and the challenges faced in managing incidents and preventing fatalities. Opiate overdose victims who retain consciousness for a sustained period and recognize the negative signs and symptoms of overdosing could summon help or self-administer naloxone, thus indicating that opiate overdose training should incorporate self-management strategies., (© 2016 Society for the Study of Addiction.)

Context: Take-home naloxone is increasingly provided to prevent heroin overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection. Some clinicians supply improvised nasal naloxone kits (outside licensed approval). Is this acceptable?, Aims: (1) To consider provision of improvised nasal naloxone in clinical practice and (2) to search for evidence for pharmacokinetics and effectiveness (versus injection)., Methods: (1) To document existing nasal naloxone schemes and published evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane, EMBASE and MEDLINE databases and 18 records included in narrative synthesis). (2) To analyse ongoing studies investigating nasal naloxone (WHO International Clinical Trials Registry Platform and US NIH RePORT databases)., Findings: (1) Multiple studies report overdose reversals following administration of improvised intranasal naloxone. (2) Overdose reversal after nasal naloxone is frequent but may not always occur. (3) Until late 2015, the only commercially available naloxone concentrations were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25 ml of fluid per nostril. The only published study of pharmacokinetics and bioavailability finds that nasal naloxone has poor bioavailability. QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability data for nasal naloxone not available before incorporation into standard clinical practice? (2) Does nasal naloxone have the potential to become a reliable clinical formulation? (3) What pre-clinical and clinical studies should precede utilization of novel naloxone formulations as standard emergency medications?, Conclusions: The addictions treatment field has rushed prematurely into the use of improvised nasal naloxone kits. Evidence of adequate bioavailability and acceptable pharmacokinetic curves are vital preliminary steps, especially when effective approved formulations exist., (© 2016 Society for the Study of Addiction.)

Aim: A counterfactual model was used to estimate the number of fatal opioid-related poisonings prevented by public treatment services for opioid use disorder (OUD) in England between April 2008 and March 2011., Methods: Patient OUD treatment episode data recorded by the English National Drug Treatment Monitoring System were linked to data on opioid deaths recorded by the Office for National Statistics. The source population was the official estimate of non-medical opioid users (aged 15-64 years; approximately 260 000 each year). The target population was all individuals (aged 15-64 years) treated for OUD in the study period (n = 220 665). The outcome measure was fatal opioid-related poisoning (opioid death). The opioid death rate [per 100 person-years (PY)] and mortality rate ratios (MRR) were computed for study year, age group (15-24, 25-34, 35-64 years) and for three treatment-related states: time spent 'prior to treatment', 'during treatment' and 'after treatment'., Results: Between April 2008 and March 2011, there were 3731 opioid deaths in the study: 741 during treatment (0.20 per 100 PY; referent category); 2722 prior to treatment [0.77 per 100 PY; MRR = 3.76, 95% confidence interval (CI) = 3.18-4.44]; and 268 after treatment (0.41 per 100 PY; MRR = 1.99, 95% CI = 1.64-2.41). By counterfactual estimation, national OUD treatment services prevented an average of 880 opioid deaths each year (95% CI = 702-1084)., Conclusions: Between April 2008 and March 2011, a counterfactual model shows that the English public treatment system for opioid use disorder prevented an average of 880 deaths each year from opioid-related poisoning. Counterfactual models of mortality prevention can be used for outcome and performance monitoring of substance use disorder treatment systems., (© 2015 Society for the Study of Addiction.)

Aims: To describe characteristics of participants and overdose reversals associated with a community-based naloxone distribution program and identify predictors of obtaining naloxone refills and using naloxone for overdose reversal., Design: Bivariate statistical tests were used to compare characteristics of participants who obtained refills and reported overdose reversals versus those who did not. We fitted multiple logistic regression models to identify predictors of refills and reversals; zero-inflated multiple Poisson regression models were used to identify predictors of number of refills and reversals., Setting: San Francisco, California, USA., Participants: Naloxone program participants registered and reversals reported from 2010 to 2013., Measurements: Baseline characteristics of participants and reported characteristics of reversals., Findings: A total of 2500 participants were registered and 702 reversals were reported from 2010 to 2013. Participants who had witnessed an overdose [adjusted odds ratio (AOR)=2.02, 95% confidence interval (CI)= 1.53-2.66; AOR = 2.73, 95% CI = 1.73-4.30] or used heroin (AOR = 1.85, 95% CI =  1.44-2.37; AOR = 2.19, 95% CI = 1.54-3.13) or methamphetamine (AOR=1.71, 95% CI=1.37-2.15; AOR=1.61, 95% CI=1.18-2.19) had higher odds of obtaining a refill and reporting a reversal, respectively. African American (AOR = 0.63, 95% CI = 0.45-0.88) and Latino (AOR = 0.65, 95% CI =  0.43-1.00) participants had lower odds of obtaining a naloxone refill, whereas Latino participants who obtained at least one refill reported a higher number of refills [incidence rate ratio (IRR) = 1.33 (1.05-1.69)]., Conclusions: Community naloxone distribution programs are capable of reaching sizeable populations of high-risk individuals and facilitating large numbers of overdose reversals. Community members most likely to engage with a naloxone program and use naloxone to reverse an overdose are active drug users., (© 2015 Society for the Study of Addiction.)

Aims: To describe work undertaken over a 20-year period, investigating overdose characteristics among survivors, effects of acute heroin administration, clustering of risk of overdose fatality and potential interventions to reduce this fatal outcome., Methods: Privileged-access interviewers obtained data from non-treatment as well as treatment samples; experimental study of drop in oxygen saturation following heroin/opiate injection; investigation of clusterings of death following prison release and treatment termination; and study of target populations as intervention work-force, including family as well as peers, and action research built into pilot implementation., Results: Overdose has been experienced by about half of heroin/opiate misusers, with even higher proportions having witnessed an overdose, and with high levels of willingness to intervene. Heroin/opiates are associated with the majority of drug-related deaths, despite relative scarcity of use. Heroin injection causes a rapid drop in oxygen saturation, recovering only slowly over the next half hour. Deaths from drug overdose are greatly more likely on prison release and post-discharge from detoxification and other in-patient or residential settings. High levels of declared willingness to intervene are matched by active interventions. Both drug-using peers and family members show ability to improve knowledge and gain confidence from training. Audit study of take-home schemes finds approximately 10% of dispensed naloxone is used in real-life emergency situations., Conclusions: Overdose is experienced by most users, with heroin/opiates contributing disproportionately to drug overdose deaths. High-risk times (e.g. after prison release) are now clearly identified. Peers and family are a willing potential intervention work-force, but are rarely trained or given pre-supply of naloxone. Large-scale naloxone provision (e.g. national across Scotland and Wales) is now being delivered, while large-scale randomized trials (e.g. N-ALIVE prison-release trial) are finally under way. Better naloxone products and better-organized provision are needed. The area does not need more debate; it now needs proper implementation alongside good scientific study., (© 2015 Society for the Study of Addiction.)

Overdose is the leading cause of premature mortality among heroin users. We examine whether the provision of regulated and quality-controlled heroin to users in specified doses would reduce heroin overdose rates. We also address this in the context of the epidemic of prescription opioid use and deaths seen in recent years in the United States and internationally. We explore the extent to which any change in legal access to heroin would affect overdose rates, and note that this depends upon the validity of the two main assumptions that variations in illicit drug purity and/or the presence of drug contaminants are major causes of overdose. Toxicological and demographic data from studies of heroin overdose deaths do not support these assumptions. The surge in the use of pharmaceutical opioids provides an example of the legal delivery of opioids of known dosage and free of contaminants, where overdose deaths can be examined to test these assumptions. Rates of fatal opioid overdose have escalated, with increased rates of prescribing of pharmaceutical opioids. On the basis of the experience with prescription opioids, unregulated legal heroin access would not reduce overdose rates., (© 2014 Society for the Study of Addiction.)

Aim: To determine the level and changes in public opinion between 2003 and 2009 among adult Canadians about implementation of supervised injection facilities (SIFs) in Canada., Design: Population-based, telephone survey data collected in 2003 and 2009 were analysed to identify strong, weak, and intermediate support for SIFs., Setting: Ontario, Canada, Participants: Representative samples of adults aged 18 years and over., Measurements: Analyses of the agreement with implementation of SIFs in relation to four individual SIF goals and a composite measure., Findings: The final sample sizes for 2003 and 2009 were 1212 and 968, respectively. Between 2003 and 2009, there were increases in the proportion of participants who strongly agreed with implementing SIFs to: reduce neighbourhood problems (0.309 versus 0.556, respectively); increase contact of people who use drugs with health and social workers (0.257 versus 0.479, respectively); reduce overdose deaths or infectious disease among people who use drugs (0.269 versus 0.482, respectively); and encourage safer drug injection (0.213 versus 0.310, respectively). Analyses using a composite measure of agreement across goals showed that 0.776 of participants had mixed opinions about SIFs in 2003, compared with only 0.616 in 2009. There was little change among those who strongly disagreed with all SIF goals (0.091 versus 0.113 in 2003 and 2009, respectively)., Conclusions: Support for implementation of supervised injection facilities in Ontario, Canada increased between 2003 and 2009, but at both time-points a majority still held mixed opinions., (© 2014 Society for the Study of Addiction.)

Aims: To evaluate a heroin overdose management training programme for family members based on emergency recovery procedures and take-home naloxone (THN) administration., Design: A two-group, parallel-arm, non-blinded, randomized controlled trial of group-based training versus an information-only control., Setting: Training events delivered in community addiction treatment services in three locations in England., Participants: A total of 187 family members and carers allocated to receive either THN training or basic information on opioid overdose management (n = 95 and n = 92, respectively), with 123 participants completing the study., Measurements: The primary outcome measure was a self-completion Opioid Overdose Knowledge Scale (OOKS; range 0-45) and an Opioid Overdose Attitudes Scale (OOAS; range 28-140) was the secondary outcome measure. Each group was assessed before receiving their assigned condition and followed-up 3 months after. Events of witnessing and managing an overdose during follow-up were also recorded., Findings: At follow-up, study participants who had received THN training reported greater overdose-related knowledge relative to those receiving basic information only [OOKS mean difference, 4.08 (95% confidence interval, 2.10-6.06; P < 0.001); Cohen's d = 0.74 (0.37-1.10)]. There were also more positive opioid overdose-related attitudes among the trained group at follow-up [OOAS mean difference, 7.47 (3.13-11.82); P = 0.001; d = 0.61 (0.25-0.97)]. At the individual level 35 and 54%, respectively, of the experimental group increased their knowledge and attitudes compared with 11 and 30% of the control group. During follow-up, 13 participants witnessed an overdose with naloxone administered on eight occasions: five among the THN-trained group and three among the controls., Conclusions: Take-home naloxone training for family members of heroin users increases opioid overdose-related knowledge and competence and these benefits are well retained after 3 months., (© 2013 Society for the Study of Addiction.)

Aims: To assess heroin injectors' perceptions of and responses to a warning issued by public health officials regarding high-potency heroin and increases in fatal overdoses., Design: Semi-structured qualitative interviews., Setting: Vancouver, Canada., Participants: Eighteen active heroin injectors., Measurements: Semi-structured interview guide focussing on heroin injectors' perceptions of and responses to the overdose warning, including reasons for failing to adhere to risk reduction recommendations., Findings: Although nearly all participants were aware of the warning, their recollections of the message and the timing of its release were obscured by on-going social interactions within the drug scene focussed on heroin quality. Many injection drug users reported seeking the high potency heroin and nearly all reported no change in overdose risk behaviours. Responses to the warning were shaped by various social, economic and structural forces that interacted with individual behaviour and undermined efforts to promote behavioural change, including sales tactics employed by dealers, poverty, the high cost and shifting quality of available heroin, and risks associated with income-generating activities. Individual-level factors, including emotional suffering, withdrawal, entrenched injecting routines, perceived invincibility and the desire for intense intoxication also undermined risk reduction messages., Conclusions: Among heroin injectors in British Columbia, a 2011 overdose warning campaign appeared to be of limited effectiveness and also produced unintended negative consequences that exacerbated overdose risk., (© 2013 Society for the Study of Addiction.)

Aims: This study investigates how age of opioid users is related to causes of death prior to, during and after opioid maintenance treatment (OMT), and estimates risks of death from various causes in relation to age., Design, Setting and Participants: Data on all opiate dependents in Norway (1997-2003) who applied for and were accepted for OMT (n = 3789) were cross-linked with the Norwegian death register. The total observation time was 10 934 person-years., Findings: A total of 213 deaths was recorded. Of these, 73% were subject to autopsy, and causes of death were known for 208 cases: the overall death rate was 1.9%. Deaths were due to drug overdose (54%), somatic (32%) and traumatic causes (14%). Overdose deaths among all age groups were reduced during OMT but age had a differential effect upon risk when out of treatment. Younger opioid users were at greater risk of overdose before entering treatment; older users were at greater risk after leaving treatment. Older OMT patients were at higher risk of both somatic and traumatic deaths, and deaths during OMT were most likely to be due to somatic causes., Conclusions: The high rates of overdose prior to and after treatment emphasize the need to provide rapid access to OMT, to retain patients in treatment and to re-enrol patients. The high prevalence among older patients of deaths due to somatic causes has implications for screening, treatment and referral, and may also lead to increased treatment costs.

Background: Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality., Methods: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for 10,208 person-years in treatment and 2,914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment., Results: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8-5.4] and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period., Conclusions: We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use.

Objectives: To describe the circumstances and draft a typology of drug-related overdose deaths., Setting: London, 2003., Methods: An audit of 148 drug overdose deaths (involving heroin, methadone, dihydrocodeine, cocaine, amphetamine or MDMA) investigated by coroners during 2003. Information extracted on toxicology, pathology and circumstances were used to identify drug(s) implicated in the death., Results: Poly- or multiple drug use was detected in the majority of deaths with at least 69 different combinations, including 66% for heroin and 42% for cocaine. Six categories of death were identified involving an opiate (100, 68%); cocaine (14, 9%); other controlled drug (five, 3%); mixed drug overdose (18, 12%); other prescribed drug (five, 3%); and other causes (seven, 5%). A witness was present and the death was not instantaneous in 92 (61%) cases, although evidence in the coronial file suggested that in the majority of cases the overdose went unnoticed until too late to intervene. In all, 15 (one in 10) of the deceased were released from prison within 3 months of death; and 37 (one in four) were reported as in receipt of a methadone prescription., Conclusions: Perhaps for the first time in the United Kingdom cocaine was detected in more drug overdose deaths than methadone. However, reducing heroin use is central to the prevention of drug-related deaths. We recommend that overdose prevention encompasses strategies to encourage a 'mutual duty of care' among problem drug users, and in the United Kingdom further investigation of the relationship of methadone treatment failures on overall trends in drug-related deaths is merited.