Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study.

BACKGROUND: Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD. METHODS: The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022-2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients' courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling. DISCUSSION: The project's primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers. TRIAL REGISTRATION: The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK), ref.nr.:195733.

Factors associated with gaps in naloxone knowledge: evidence from a 2022 great plains survey.

BACKGROUND: The rising prevalence of fast-acting opioids in the USA suggests the increased need for non-professional first responder administration of naloxone. Effective administration of naloxone during an overdose requires that bystanders are familiar with, have access to, and know how to use naloxone. METHODS: Drawing on a statewide, address-based sample of Nebraskan adults, we used logistic regression to predict the likelihood of respondents' familiarity with, access to, and competency to administer naloxone. Our independent variables included measures indicating proximity to drug use, perceived community stigma toward people who use drugs, and demographic data. RESULTS: There were significant gaps in naloxone knowledge in Nebraska. Although 74.8% of respondents were familiar with naloxone, only 18.2% knew how to access it and 18.0% knew how to use it. Being close to an overdose experience, lifetime illicit opioid use, being close to a person who uses opioids, and having access to illicit opioids were not significantly associated with naloxone familiarity, access, or competency among respondents in Nebraska's two largest cities, Omaha and Lincoln. Outside of these cities, being close to a past overdose experience and access to illicit opioids was associated with higher odds of naloxone access and competency, but lifetime opioid use and being close to a person who uses opioids were not. Finally, among those familiar with naloxone, a higher perception of community stigma toward people who use opioids generally was associated with lower odds of naloxone access and competency. Higher perception of community stigma toward people who use heroin, methamphetamines, and cocaine, however, was associated with higher odds of naloxone access. CONCLUSIONS: Our findings highlight the continued need for education on naloxone with a specific focus on access and competency to further reduce opioid-related overdose deaths. Specific focus should be placed on promoting naloxone knowledge among people with a higher likelihood of needing to administer naloxone to reduce otherwise avoidable deaths. Further work is needed to understand differences in the relationship between substance-specific perceived stigma and its association with naloxone access.

Predictors of concurrent heroin use among patients on opioid maintenance treatment in France: a multilevel study over 11 years.

BACKGROUND: Consistent reports from health professionals suggest that heroin is commonly used by patients undergoing opioid maintenance treatment (OMT) in France, potentially jeopardizing their recovery process. However, there has been no formal epidemiological assessment on the matter. METHODS: We use a yearly updated compendium retrieving information on patients admitted in treatment centres in France between 2010 and 2020. Given the hierarchical nature of the data collection, we conduct 2-level modified Poisson regressions to estimate the risks of past month heroin use among patients on OMT. RESULTS: Despite an overall decreasing trend over time, heroin use among patients on OMT is indeed common, with half of patients declaring concurrent use. Our study unveils differentiated risks of heroin use vary according to the type of OMT, with patients on methadone more likely to use heroin compared to those on buprenorphine. The use of multilevel-related measures also uncovers high heterogeneity among patients' profiles, reflecting different stages in the treatment process, as well as differentiated practices across treatment centres. CONCLUSION: Opioid maintenance treatment is associated with heroin use, in particular when methadone is involved. The heterogeneity among patients on OMT should be given particular attention, as it underscores the need for tailored interventions.

The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

OBJECTIVE: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. METHODS: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. RESULTS: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. CONCLUSIONS: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Who receives heroin-assisted treatment? A comparison of patients receiving opioid maintenance treatment in Denmark.

BACKGROUND: Since 2010, heroin-assisted treatment (HAT) has been one of the treatment options available to people with opioid use disorder (OUD) in Denmark. This study aimed to characterize HAT patients at treatment start and compare their individual characteristics to those of patients entering traditional opioid maintenance treatment (OMT) with methadone or buprenorphine during the same period. METHODS: Patients who initiated HAT or OMT with methadone or buprenorphine in Denmark from 2010 to 2018 were included (n=6798). Multiple national registers were linked to compare treatment groups in terms of socio-demographic variables, previous OUD treatment episodes, hospital-based care, and criminal conviction history. RESULTS: Nearly all HAT patients had a history of methadone treatment (91%) and half had residential treatment experience (48%). In the year previous to admission, HAT patients recorded the highest percentages of non-fatal overdoses (12%) and chronic hepatitis C diagnoses (16%), and the lowest percentages of psychiatric disorders (11%) compared to traditional OMT patients. Criminal convictions were also common: 39% of the HAT group had committed a property crime and 18% a drug-related crime the year before HAT entry. During the study period, an overall reduction in OMT enrollments for each year was recorded. The HAT proportion to the total remained fairly stable (4%-10%), while the buprenorphine proportion increased. CONCLUSIONS: In Denmark, OMT patients exhibited numerous vulnerabilities at treatment start, and among the patient groups, HAT patients were the most burdened. HAT seems to reach the target group and adhere to formulated eligibility criteria.

DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment.

BACKGROUND: Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). METHODS: 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. RESULTS: Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. CONCLUSION: DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.

Individual-Level Risk Prediction of Return to Use During Opioid Use Disorder Treatment.

Importance: No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder. Objective: To develop an individual-level prediction tool for risk of return to use in opioid use disorder. Design, Setting, and Participants: This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities. Intervention: All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. Main Outcomes and Measures: Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment. Results: The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84). Conclusions and Relevance: The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Opioid-related deaths and their counterpart by occurrence era, age group and coimplicated drugs: Scotland vs. England and Wales.

AIMS: Compare by occurrence era and age group how opioid-related deaths (ORDs) and their counterpart evolved in Scotland vs. England and Wales during 2006-2020. For Scotland, compare coimplication rates between ORDs and non-ORDs for any benzodiazepine, cocaine or gabapentin/pregabalin, and consider whether coimplication in ORDs depended on opioid-specificity. METHODS: Cross-tabulations of drug misuse deaths (DMDs) obtained by 3 yearly occurrence era (2006-2008 to 2018-2020) and age group (under 25, 25-34, 35-44, 45-54, 55+ years) for England and Wales and subdivided by whether at least 1 opiate was mentioned on death certificate (DMD-Os or not); and of Scotland's opioid-related deaths (ORDs vs. non-ORDs) together with (i) coimplication by any benzodiazepine, cocaine or gabapentin/pregabalin; and (ii) opioid-specificity of ORDs. ORD is defined by heroin/morphine, methadone or buprenorphine being implicated in DMD. RESULTS: Per era between 2012-2014 and 2018-2020, Scotland's ORDs increased by 54% and non-ORDs by 34%. Increase in DMD-Os in England and Wales was more modest. Cocaine was implicated in 83% of Scotland's 2690 non-ORDs during 2006-2020; and any benzodiazepine in 53% of 8409 ORDs. However, in 2018-2020, coimplication rates in 2926 ORDs (880 non-ORDs) were 81% (33%) for any benzodiazepine, 30% (74%) for cocaine and 38% (22%) for gabapentin/pregabalin. Coimplication rate in 2018-2020 for any benzodiazepine was lowest at 70% (616/877) for heroin/morphine ORDs; and, by age group, at 66% (160/241) for ORDs aged 55+ years. CONCLUSIONS: Drug testing to inform users, shared intelligence between police and public health for earlier detection of changes in supply and monitoring of prescribed daily-dose of methadone are urgent.

Association of medications for opioid use disorder with reduced risk of repeat opioid overdose in Medicaid: A cohort study.

INTRODUCTION: Following a nonfatal opioid overdose, patients are at high risk for repeat overdose. The objective of this study was to examine the association of MOUD after nonfatal opioid overdose with risk of repeat overdose in the following year. METHODS: This retrospective cohort study analyzed Missouri Medicaid claims from July 2012 to December 2021. The study identified opioid overdoses occurring between 2013 and 2020 using diagnosis codes for opioid poisoning in an inpatient or emergency department setting. The study implemented Cox models with a time-varying covariate for post-overdose receipt of MOUD. RESULTS: During the study period, MOUD receipt after overdose more than tripled, from 4.8 % to 18.9 %. Overall, only 12.1 % of patients received MOUD in the year after index. MOUD during follow-up was associated with significantly lower risk of repeat overdose (HR = 0.34, 95 % CI = 0.14-0.82). Out of 3017 individuals meeting inclusion criteria, 13.6 % had a repeat opioid overdose within 1 year. Repeat overdose risk was higher for those whose index overdose involved heroin or synthetic opioids (HR = 1.71, 95 % CI = 1.35-2.15), but MOUD was associated with significantly reduced risk in this group (HR = 0.34, 95 % CI = 0.13-0.92). CONCLUSIONS: MOUD receipt was associated with reduced risk of repeat overdose. Those whose index overdoses involved heroin or synthetic opioids were at greater risk of repeat overdose, but MOUD was associated with reduced risk in this group.

Exploring Patients' Perceptions on Injectable Opioid Agonist Treatment: Influences on Treatment Initiation and Implications for Practice.

INTRODUCTION: Injectable opioid agonist treatment (iOAT) with diacetylmorphine is an effective option for individuals previously considered non-responsive to opioid substitution treatment. Despite implementation in Canada and several European countries, relatively few eligible people choose to initiate iOAT. To better understand what encourages or deters prospective patients from initiating iOAT, the current study explores patients' perceptions on iOAT and how these influence therapy initiation in practice. METHODS: We conducted 34 semi-structured interviews with individuals currently in or eligible for iOAT in two German outpatient iOAT clinics. Transcripts were analysed following qualitative content analysis, with development of inductive categories and use of consensual coding. For member checking, we consulted individuals with lived experiences prior to data collection and publication. RESULTS: Participants based their choice to initiate iOAT on the perceived implications of the treatment on one's daily life and individual recovery. Participants were encouraged to initiate iOAT due to the therapy's perceived potential in reducing cravings and substance use, its positive health consequences, and due to the image of iOAT as a path towards abstinence. Regarding deterring perceptions, participants feared a profound impairment of daily life due to factors such as the daily visits to the clinic, were concerned about whether iOAT would sufficiently promote or even impede one's recovery, and described negative health effects. CONCLUSION: Perceptions found in this study profoundly influenced participants' decisions on iOAT enrolment and contextualize the previous literature. The study reveals the dynamic coexistence of different perceptions about iOAT and sheds light on the inner-group stigmatization of iOAT. Practitioners and future research should acknowledge the complexities found in the current study in order to exploit the full potential of effective treatment modalities such as iOAT.

Xylazine Adulteration of the Heroin-Fentanyl Drug Supply : A Narrative Review.

Xylazine is an animal sedative, approved by the U.S. Food and Drug Administration, that is commonly used in veterinary medicine and is not approved for human use. Since 2016, xylazine has consistently appeared in the illicitly manufactured fentanyl supply and has significantly increased in prevalence, likely due to its low cost, easy availability, and presumed synergistic psychoactive effect. Clinical experience along with the available pertinent research were used to review xylazine adulteration of the drug supply and provide guidance on the care of patients exposed to xylazine. This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds.

Correlates of nonfatal overdose among treatment-seeking individuals with non-heroin opioid use disorder: Findings from a pragmatic, pan-Canadian, randomized control trial.

INTRODUCTION: Misuse of prescription and synthetic opioids is a primary contributor to the escalating overdose crisis in North America. However, factors associated with nonfatal overdose (NFO) in this context are poorly understood. We examined individual and socio-structural level correlates of NFO among treatment-seeking adults with an opioid use disorder (OUD) not attributed to heroin (nonheroin opioid use disorder [NH-OUD]). METHODS: The study drew data from OPTIMA, a pan-Canadian, multicenter, pragmatic, two-arm randomized control trial comparing supervised methadone and flexible take-home dosing buprenorphine/naloxone models of care among adults with NH-OUD conducted between 2017 and 2020. We used bivariable and multivariable logistic regression to determine factors associated with a lifetime history of NFO among participants enrolled in the trial. RESULTS: Of 267 included participants, 154 (58%) reported a NFO in their lifetime, of whom 83 (55 %) had an NFO in the last 6 months. In multivariable analyses, positive urine drug test (UDT) for methamphetamine/amphetamine (Adjusted Odds Ratio [AOR] = 2.59; 95 % confidence interval [CI]: 1.17-5.80), positive UDT for fentanyl (AOR = 2.31; 95 % CI: 1.01-5.30), receiving income assistance (AOR = 2.17; 95 % CI: 1.18-4.09) and homelessness (AOR = 2.40; 95 % CI: 1.25-4.68) were positively associated with a lifetime history of NFO. CONCLUSIONS: We found a high prevalence of NFO history in treatment-seeking adults with NH-OUD, particularly among participants with certain drug use patterns and markers of socio-structural marginalization at the time of enrollment. Given the known impact of prior NFO on future harms, these findings highlight the need for comprehensive care approaches that address polysubstance use and social determinants of health to mitigate future overdose risk.

Concomitant Drug Use among Opioid-Dependent Patients with and without Attention Deficit Hyperactivity Disorder: Does Methylphenidate Merit a Trial?

INTRODUCTION: Concomitant drug use is common among opioid-dependent patients in maintenance therapy. Attention deficit hyperactivity disorder (ADHD), a common comorbidity among opioid users, is associated with a higher risk of concomitant drug use. Earlier studies showed that methylphenidate (MPH) can reduce cocaine consumption among patients with ADHD. The use of MPH as an agonist-replacement or maintenance therapy in cocaine-dependent patients without ADHD is also common in Switzerland, despite a lack of supporting evidence. The aim of this study was to assess concomitant cocaine, amphetamine, MDMA, MPH, and heroin use among patients in opioid maintenance therapy either with or without comorbid ADHD. We expected stimulant consumption to be higher in patients with cocaine dependence and comorbid ADHD and that use of MPH would not lead to a reduction in cocaine consumption in patients without ADHD. We therefore evaluated correlations between use of MPH and cocaine consumption and between MPH consumption and cocaine craving within the two groups. METHODS: This cross-sectional study included 94 opioid-dependent patients in maintenance therapy in an outpatient department of the Psychiatric Hospital of Zurich. The patients were divided into two groups based on comorbid ADHD; a group with ADHD (N = 27) and a group without ADHD (N = 67). Drug use was assessed using 3-month hair analysis. RESULTS: We did not find significant differences in the number of patients using cocaine, amphetamine, MDMA, or heroin between groups with or without ADHD. With respect to cocaine use, 85.2 percent of patients in the ADHD group and 73.1 percent in the non-ADHD group were users. The non-ADHD group showed a significant positive correlation between the concentration of MPH and cocaine in hair samples (p < 0.05), and a positive correlation between cocaine craving and the concentration of MPH in hair samples (p = 0.065). These two trends were not evident in the ADHD group. CONCLUSION: Among patients without ADHD, use of MPH correlates with higher cocaine consumption and craving. Conversely, no significant correlation was found between MPH and cocaine use in patients with ADHD. Our study adds to the evidence that MPH confers negative effects in cocaine users without ADHD and should thus have no place in the treatment of these patients.

Blended smartphone intervention for patients in opioid maintenance treatment in Iran: protocol for a randomized controlled trial.

BACKGROUND: The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms. OBJECTIVE: We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran. METHOD: Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models. DISCUSSION: This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT. TRIAL REGISTRATION: https://en.irct.ir/trial/53578 .

Patients' satisfaction with heroin-assisted treatment: a qualitative study.

BACKGROUND: Heroin-assisted treatment (HAT) involves supervised dispensing of medical heroin (diacetylmorphine) for people with opioid use disorder. Clinical evidence has demonstrated the effectiveness of HAT, but little is known about the self-reported satisfaction among the patients who receive this treatment. This study presents the first empirical findings about the patients' experiences of, and satisfaction with, HAT in the Norwegian context. METHODS: Qualitative in-depth interviews with 26 patients in HAT were carried out one to two months after their enrollment. Analysis sought to identify the main benefits and challenges that the research participants experienced with this treatment. An inductive thematic analysis was conducted to identify the main areas of benefits and challenges. The benefits were weighed against the challenges in order to assess the participants' overall level of treatment satisfaction. RESULTS: Analysis identified three different areas of experienced benefits and three areas of challenges of being in this treatment. It outlines how the participants' everyday lives are impacted by being in the treatment and how this, respectively, results from the treatment's medical, relational, or configurational dimensions. We found an overall high level of treatment satisfaction among the participants. The identification of experienced challenges reveals factors that reduce satisfaction and thus may hinder treatment retention and positive treatment outcomes. CONCLUSIONS: The study demonstrates a novel approach to qualitatively investigate patients' treatment satisfaction across different treatment dimensions. The findings have implications for clinical practice by pointing out key factors that inhibit and facilitate patients' satisfaction with HAT. The identified importance of the socio-environmental factors and relational aspect of the treatment has further implications for the provision of opioid agonist treatment in general.

'This is hardcore': a qualitative study exploring service users' experiences of Heroin-Assisted Treatment (HAT) in Middlesbrough, England.

BACKGROUND: Heroin-Assisted Treatment (HAT) is well evidenced internationally to improve health and social outcomes for people dependent on opioids who have not been helped by traditional treatment options. Despite this evidence base, England has been slow to implement HAT. The first service outside of a trial setting opened in 2019, providing twice-daily supervised injections of medical-grade heroin (diamorphine) to a select sample of high-risk heroin users in Middlesbrough. This paper explores their experiences, including the negotiation of the strict regularly controls required of a novel intervention in the UK context. METHODS: We conducted in-depth interviews with service providers and users of the Middlesbrough HAT service between September and November 2021. Data from each group were thematically analysed and reported separately. This paper details the experiences of the twelve heroin dependent men and women accessing HAT. RESULTS: Participants' accounts of HAT treatment evidenced a tension between the regulatory constraints and uncertainty of treatment provision, and the positive outcomes experienced through supportive service provision and an injectable treatment option. Limited confidence was held in treatment efficacy, longevity of funding, and personal capacity for treatment success. This was counteracted by a strong motivation to cease engagement with the illicit drug market. While attendance requirements placed restrictions on daily activities, participants also experienced benefits from strong, supportive bonds built with the service providers through their continued engagement. CONCLUSIONS: The Middlesbrough HAT programme provided benefits to a high-risk population of opioid dependent people who were unable or disinclined to participate in conventional opioid substitution treatments. The findings in this paper highlight the potential for service modifications to further enhance engagement. The closure of this programme in 2022 prohibits this opportunity for the Middlesbrough community, but holds potential to inform advocacy and innovation for future HAT interventions in England.

Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats.

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

Heroin assisted treatment for key health outcomes in people with chronic heroin addictions: A context-focused systematic review.

BACKGROUND AND AIMS: Randomised controlled trials in Europe and Canada have shown that supervised heroin assisted treatment (HAT) is an effective treatment option for people with long-term heroin addictions for whom the standard opioid substitution treatments (OST) have not been effective. This review aims to evaluate the effectiveness of supervised HAT and analyse the significance of context and implementation in the design of successful HAT programmes. METHODS: PubMed, CENTRAL, Embase, and Web of Science were searched to identify randomised controlled trials (RCT) and systematic reviews evaluating supervised HAT compared to any other OST. Studies were eligible for inclusion if they were published in English, evaluated a supervised form of HAT, and included illegal drug use and/or health as a primary outcome measure. There were no restrictions on publication date. The following outcomes of the included studies were analysed using narrative synthesis and meta-analysis where possible: retention, street drug use, health, and social functioning. RESULTS: Nine randomised controlled trials spanning eight studies (n = 2331) and three systematic reviews met the inclusion criteria. Seven of the eight studies compared HAT to methadone maintenance treatment (MMT). One study compared HAT to injectable hydromorphone in a double-blind non-inferiority trial. Meta-analysis was performed on pooled results of retention across all included studies and found that HAT has a statistically significant effect on retention [Z = 7.65 (P > 0.0001)]. Five of the eight included studies found that supervised HAT reduces participants' use of illegal drugs more significantly than MMT. Evidence of improved health in participants receiving supervised HAT compared to other OSTs was inconsistent; positive effects were observed in three of the included studies (n = 1626). CONCLUSION: When compared to methadone maintenance treatment (MMT), heroin assisted treatment (HAT) more consistently retains people with heroin addictions in treatment and reduces their consumption of illicit drugs. TRIAL REGISTRATION: PROSPERO registration: CRD42022341306.

Changing Landscape of Fentanyl/Heroin Use and Distribution.

OBJECTIVE: To understand the geopolitics of the supply of fentanyl and heroin. RESULTS: In our practice, the percent of fentanyl positive drug tests increased from years 2016 to 2022, but heroin positive drug tests decreased by 80% in the same period. CONCLUSION: Fentanyl has replaced heroin as a street drug for opioid dependent drug users.

Naloxone expansion is not associated with increases in adolescent heroin use and injection drug use: Evidence from 44 US states.

BACKGROUND: Naloxone distribution is central to ongoing efforts to address the opioid overdose crisis. Some critics contend that naloxone expansion may inadvertently promote high-risk substance use behaviors among adolescents, but this question has not been directly investigated. METHODS: We examined relationships between naloxone access laws and pharmacy naloxone distribution with lifetime heroin and injection drug use (IDU), 2007-2019. Models generating adjusted odds ratios (aOR) and 95% confidence intervals (CI) included year and state fixed effects, controlled for demographics and sources of variation in opioid environments (e.g., fentanyl penetration), as well as additional policies expected to impact substance use (e.g., prescription drug monitoring). Exploratory and sensitivity analyses further examined naloxone law provisions (e.g., third-party prescribing) and applied e-value testing to assess vulnerability to unmeasured confounding. RESULTS: Adoption of any naloxone law was not associated with changes in adolescent lifetime heroin or IDU. For pharmacy dispensing, we observed a small decrease in heroin use (aOR: 0.95 [CI: 0.92, 0.99]) and a small increase in IDU (aOR: 1.07 [CI: 1.02, 1.11]). Exploratory analyses of law provisions suggested that third-party prescribing (aOR: 0.80, [CI: 0.66, 0.96]) and non-patient-specific dispensing models (aOR: 0.78, [CI: 0.61, 0.99]) were associated with decreased heroin use but not decreased IDU. Small e-values associated with the pharmacy dispensing and provision estimates indicate that unmeasured confounding may explain observed findings. CONCLUSION: Naloxone access laws and pharmacy naloxone distribution were more consistently associated with decreases rather than increases in lifetime heroin and IDU among adolescents. Our findings therefore do not support concerns that naloxone access promotes high-risk adolescent substance use behaviors. As of 2019, all US states have adopted legislation to improve naloxone access and facilitate use. However, further removal of adolescent naloxone access barriers is an important priority given that the opioid epidemic continues to affect people of all ages.