Polysubstance use (PSU), particularly opioid-involved and stimulant-involved PSU, is a growing issue in the USA. PSU increases the risk of negative health consequences, including infectious diseases, worsening physical and mental health conditions, and overdose-related deaths. These consequences occur in the context of varying health risk behaviours, substance-related preferences, and treatment engagements among people with PSU. To inform improvements in prevention, harm reduction, and substance use disorder (SUD) treatment, additional research is needed to comprehensively understand the current context and drivers of PSU preferences, motivations, and behaviours.

Herein, we describe the protocol for a prospective cohort study designed to capture detailed patterns, profiles, and trajectories of PSU, with the aim of comprehensively examining the drivers of PSU behaviours and SUD treatment utilisation. Adults (ages 18–75; n=400) who engage in PSU will be recruited from healthcare institutions, an established participant database maintained by an adjacent SUD research team, and online advertisements. Study assessments will capture dynamic patterns, choice preferences, and motivators of PSU via behavioural economic (BE) measures, detailed Timeline Follow-Back (TLFB) interviews, and self-administered surveys. The assessment timeline will include a baseline survey and TLFB interview, weekly TLFB interviews for 4 weeks post-baseline, and follow-up surveys and TLFB interviews at 4-, 8-, and 12-months post-baseline.

The study is funded through the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative and was approved by the University of Michigan Medical Institutional Review Board. Findings will be disseminated to academic, clinical, and community partners through the Michigan Innovations in Addiction Care through Research and Education programme. Results from this study will inform actionable and practical insights relevant to the delivery of personalised care in the context of PSU.

The USA is facing a substance use workforce crisis, due in part to a shortage of providers. Substance use peer workers (PWs) fill a critical gap in the care continuum and are a growing sector of the workforce. In their daily work of providing non-clinical services to highly vulnerable people who use drugs, PWs are repeatedly exposed to stress, trauma and loss, which can adversely affect their well-being and recovery. This review aims to synthesise available evidence on PWs’ experiences working in the field, its impact on their recovery and their occupational support needs.

We will conduct a qualitative systematic review using the PRISMA flow diagram to illustrate article identification and screening. We will search six databases (Academic Search Complete, APA PsycInfo, CINAHL, MEDLINE, SocINDEX, PubMed) for English-language peer-reviewed scientific literature published between January 1, 2000, and August 13, 2025. Eligible articles must primarily focus on PWs’ perspectives and experiences related to working in the field and the impact of this work on their recovery. Article screening and data extraction will be conducted independently by two trained research assistants and supervised by a third researcher who will resolve any disagreements. We will use a thematic synthesis approach to synthesise findings of included articles and report synthesised findings in accordance with Enhancing Transparency in Reporting the Synthesis of Qualitative Findings guidelines. We will assess article quality using the CASP Qualitative Checklist and assess our confidence in individual review findings using the GRADE-CERQual approach.

Ethics approval is not required, as the research only involves published work. Findings will be disseminated via peer-reviewed publication, conference presentations and online via social media.

CRD420251105491

Alcohol use disorder (AUD) is a prevalent, chronic condition generating considerable global morbidity, mortality and socioeconomic burden. Despite the availability of established pharmacotherapies, overall treatment uptake remains low and effect sizes are moderate at best. Emerging evidence highlights substantial differences in treatment response between sexes and genders, yet these factors are rarely systematically considered in clinical trials or routine care. Existing reviews have limited scope and often exclude gender-diverse populations. This project aims to (1) Synthesise evidence on gender- and sex-specific efficacy, safety and adherence in AUD pharmacotherapies, (2) Evaluate the consideration of sex and gender beyond binary classifications in existing research and (3) Develop recommendations for gender- and sex-sensitive treatment strategies.

A systematic review and meta-analysis will be conducted using (PubMed, Web of Science, Scopus, Google Scholar, German Clinical Trials Register and ClinicalTrials.gov). We will include randomised controlled trials of pharmacotherapies for AUD with a minimum treatment duration of 4 weeks, reporting gender-specific and/or sex-specific results. The literature search will cover studies published up to October 2025, with inclusion restricted to articles published in English or German, regardless of setting. Two reviewers will independently screen records and assess risk of bias (Cochrane RoB), with evidence certainty evaluated using Grading of Recommendations Assessment, Development and Evaluation and aligned to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Sex and Gender Equity in Research guidelines.

Ethics approval is not required as only data from already completed studies and supplementary information directly provided by study authors are used. Findings and recommendations will be disseminated in peer-reviewed journals and presented at conferences and workshops.

CRD420251079160.

Harms due to methamphetamine use disorder (MAUD) are rising globally. Untreated withdrawal symptoms perpetuate the cycle of dependence and are a barrier to treatment. There is no pharmacotherapy approved for methamphetamine withdrawal. Lisdexamfetamine (LDX) dimesylate has potential as an agonist therapy to ameliorate symptom severity during acute methamphetamine withdrawal and increase duration of initial abstinence and retention in treatment.

We will conduct a double-blind, randomised, controlled trial to evaluate the efficacy of LDX in reducing symptom severity during acute methamphetamine (MA) withdrawal. One hundred eighty-four adults with moderate to severe MAUD presenting to a health service requesting MA withdrawal treatment who report use of MA within the last 72 hours will be recruited. Participants will be randomised 1:1 to receive a tapering dose of lisdexamfetamine (250 mg on day 1, reducing by 50 mg per day to 50 mg on day 5, followed by 2 days of placebo washout on days 6 and 7), or placebo for 7 days. The study will be conducted over 7 days in an inpatient unit, and all participants will also receive standard inpatient withdrawal care. Participants will be followed up in the community to day 84. The primary outcome is efficacy, defined as the between-group difference in average withdrawal severity measured over the 7-day admission by the Amphetamine Withdrawal Questionnaire. Secondary outcomes are retention in treatment, treatment satisfaction, sleep and concomitant medication use (symptomatic medications and medications for other indications to day 7); safety, craving for MA, post-treatment withdrawal symptoms, depression, anxiety and stress, insomnia and cost effectiveness (to day 28) and MA use, mental, physical and social health and post-withdrawal treatment utilisation (to day 84). A First Nations qualitative substudy will assess the experiences of Aboriginal and Torres Strait Islander participants, ensuring the treatment meets the needs of First Nations people.

This protocol was first approved by the St Vincent’s Hospital Human Research Ethics Committee on 15/05/2024 (2024/ETH00788). All participants will be provided with a participant information sheet and consent form, be fully informed about the study and given ample time to consider participation. Results will be published in peer-reviewed journals and presented at national and international conferences. Findings will be presented such that individual participants will not be identifiable.

ACTRN12624001061527.

Alcohol is consumed by an estimated 137.4 million people in the USA 12 years of age and older and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019.

The proposed review of the evidence on alcohol’s impact on health aims to produce conclusions to inform the Dietary Guidelines for Americans, 2026–2030. A multi-method approach will be utilised to formulate conclusions on (i) weekly (ie, average) thresholds to minimise long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimise the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (eg, pregnant women) and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert decisions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol’s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person’s sex and average level of alcohol use. The systematic reviews were designed in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be qualitatively analysed. The results of the public consultations will be used to further revise and refine the project’s conclusions.

The study was granted an ethics exemption as only secondary data sources and unidentifiable public consultation will be utilised. Systematic reviews are pre-registered with PROSPERO (registration numbers CRD42024584924 and CRD42024584948).

This project will establish a scientific consensus concerning alcohol’s impact on health. This consensus is imperative for informing the upcoming Dietary Guidelines for Americans, 2026–2030, and for better informing individuals about the health risks associated with alcohol use.

Our study investigated the age-adjusted incidence rates of non-fatal overdoses by HIV status and sex, and examined trends over time.

We used data from the Comparative Outcomes and Service Utilization Trends study, a population-based cohort study that includes clinical and administrative health data on virtually all people with HIV (PWH) and a 10% random sample of people without HIV in the province.

British Columbia, Canada.

Between April 2012 and March 2020, 11 050 PWH (81.8% male) and 473 952 people without HIV (50.3% male) who were 19 years and older contributed 68 035 and 3 285 824 person years (PY) of follow-up, respectively.

The primary outcome was age-adjusted incidence rates of non-fatal overdose events stratified by sex and HIV status. Trends over time were also assessed.

Age-adjusted non-fatal overdose incidence rates among males with and without HIV were 36.4 and 3.12 per 1000 PY, respectively (incidence rate ratio (IRR) = 11.7, 95% CI 10.9 to 12.5). For females with and without HIV, the age-adjusted incidence rates were 61.4 and 2.33 per 1000 PY, respectively (IRR=26.3, 95% CI 24.0 to 28.7). Between 2013 and 2019 (calendar years with full-year data), the age-adjusted non-fatal overdose rate increased significantly among males and females without HIV but not among PWH.

We observed a significantly higher non-fatal overdose rate among PWH compared to people without HIV. The rate was highest among females with HIV. These findings underline the need for policies and programmes oriented towards PWH to mitigate overdoses, especially for females.

Tobacco use causes approximately 8 million deaths worldwide each year. Against the backdrop of a rapidly expanding game market, there is growing potential to develop tailored gaming interventions for smoking cessation. This study protocol describes the development of a personalised Serious Game Applet based on an integrated TTM–PMT–HAPA framework (Transtheoretical Model, Protection Motivation Theory, Health Action Process Approach) and evaluates its effectiveness compared with conventionalShort Messaging Service (SMS) -based smoking cessation interventions.

Design: The study comprises two phases. The first involves developing the Serious Game Applet using the TTM–PMT–HAPA theoretical framework. The second phase consists of a multicentre, two-arm, single-blind cluster randomised controlled trial, which will enrol 1320 eligible smokers from various enterprises. Enterprises will be randomised to either the Serious Game Applet group or the SMS push control group. Eligible participants include daily smokers aged 18–45 years, working in non-tobacco-related enterprises, with exhaled carbon monoxide levels ≥6 ppm.

Outcomes: Primary outcomes are smoking abstinence rates at 3 and 6 months. Secondary outcomes include abstinence rates at 1, 2 and 9 months; point-prevalence cessation rates at 1, 2, 3, 6 and 9 months; changes in cigarette consumption; stage transitions in smoking cessation; nicotine dependence scores and withdrawal symptoms. The trial will be conducted as a field study targeting smartphone users across three cities in Fujian Province, China.

This study has been approved by the Biomedical Research Ethics Committee of Fujian Medical University (Approval No. 127, 2024). Results will be disseminated through peer-reviewed journals and academic conferences.

ChiCTR2400088105.

Despite the continued burden of opioid overdose in communities in the USA, effective treatments for opioid use disorder (OUD), such as medication for opioid use disorder (MOUD), remain underused. Motivational interviewing techniques and linkage to MOUD via digital health are innovative practices developed to overcome persistent barriers to accessing MOUD treatment. These practices are merged in a comprehensive digital health platform, RecoveryPad (developed by the Center for Progressive Recovery). Our study, ‘Using System Dynamics Modeling to Foster Real-time Connections to Care’ (NIH Award #: 1R61DA057675-01), is a pilot to assess the feasibility and behaviour change potential of RecoveryPad for our target audience of people experiencing OUD.

This study will recruit 40 participants in Connecticut and New York through online platforms, such as social media and digital advertising, and direct access via quick-response (QR) codes distributed by local community partners. Eligibility assessment and enrolment will be conducted virtually. Individuals reporting symptoms indicating moderate to severe OUD who are at least 18 years of age are eligible for the study, excluding those who are currently receiving MOUD, pregnant or incarcerated. Enrolled participants will interact with an automated chatbot, live recovery coaches and, if desired, be referred to a telehealth MOUD provider via the RecoveryPad platform. Participants will have access to the platform for 30 days and will be asked to complete brief surveys to assess MOUD engagement and secondary outcomes at 30 and 90 days. Additionally, system dynamics (SD) models will be developed at the individual level to simulate participant interactions with RecoveryPad, and at the community level to improve understanding of the systems affecting OUD and MOUD access.

This project received approval from the Yale University Human Investigation Committee in 2024 (HIC # 2000034414). All participants will complete an electronic consent form with detailed study information and release of information to obtain data related to MOUD appointment attendance. Findings and conclusions from this pilot will be disseminated via peer-reviewed publication, advisory board meetings and meetings with community partners.

NCT05832879.

Insomnia is a common complaint among patients with opioid use disorder (OUD) maintained on buprenorphine (BUP). However, people with OUD have historically been excluded from insomnia clinical trials, leaving clinicians without evidence-based treatment options for this patient population. Lemborexant, the Food and Drug Administration (FDA)-approved dual orexin receptor antagonist for the treatment of insomnia, was recently shown to be safe and tolerable among a sample of patients with insomnia who were maintained on BUP. We hypothesise that pharmacologically antagonising the orexin system with lemborexant may improve insomnia symptoms in individuals with OUD and also enhance BUP treatment benefits by improving performance in neurofunctional domains identified in the National Institute on Drug Abuse Phenotyping Assessment Battery.

Participants with insomnia and OUD who have been stabilised on BUP for at least 4 weeks will be randomly assigned to receive either lemborexant (n=50) or placebo (n=50) for 8 weeks. Participants will complete assessments at baseline, during the 8-week intervention, postintervention and at a 2-week follow-up. Primary outcomes are insomnia severity and impulsivity. Secondary measures include objective sleep metrics (total sleep time, sleep efficiency, sleep onset latency and wake after sleep onset) and performance in the neurofunctional domains of negative emotionality and metacognition.

The study was approved by the Virginia Commonwealth University Institutional Review Board in April 2025 (protocol number HM20031777). Data collection began in May 2025 and is expected to be completed by May 2029. The trial is conducted under FDA IND no. 154797 (FGM). The dissemination plan for the trial includes presentations at local and national conferences, submission of primary and secondary outcome manuscripts for publication in peer-reviewed journals and circulation of findings to popular media outlets, as available. Results will also be shared with interested participants and clinical collaborators upon completion of the trial.

NCT06981195.

There is limited evidence on how to effectively treat individuals from marginalised populations with dependence on amphetamine and/or methamphetamine (collectively referred to hereafter as amphetamine dependence). The disease burden is extremely high in this population, especially related to psychiatric comorbidities, cardiovascular complications, injection-related infections and poor social functioning. ATLAS4Dependence is a multi-centre randomised, placebo-controlled, double-blind trial that will investigate the effectiveness and safety of substitution treatment with dextroamphetamine compared with placebo in people with amphetamine dependence.

The trial will recruit 226 adult patients in several outpatient clinics in Norway.Inclusion criteria comprise individuals with amphetamine dependence, defined as use on three or more days per week during the past 28 days, who currently inject or have formerly injected drugs. This includes individuals both with and without comorbid opioid dependence, as well as those currently receiving or not receiving opioid agonist treatment. Participants will be randomly assigned 1:1 to receive either dextroamphetamine or placebo for 12 weeks. Flexible doses within the range of 30–120 mg daily will be provided based on individual assessments. The participants in both arms will be offered standard psychosocial and medical follow-up in accordance with current clinical practice. The endpoint assessments will be conducted at 12 weeks with weekly self-reports and safety assessments and a follow-up assessment at 52 weeks. The primary objective of the study is to assess the impact of 12 weeks daily prescribed oral dextroamphetamine versus placebo on the use of illicit amphetamines as well as on the total amount of amphetamines used (including both illicit and prescribed sources). Secondary outcomes are the differences between the groups at 12 weeks regarding psychological distress, symptoms of psychosis, quality of life, cardiovascular risk factors, injection-related infections, executive functioning, attention-deficit hyperactivity disorder-related symptoms, sleep, violence risk, fatigue, symptoms of craving and withdrawal, treatment retention, days of use of illicit amphetamines and use at 4 weeks and 8 weeks during the intervention period, use of other illicit substances and alcohol, as well as a cost-effectiveness analysis (using private economy, criminal activity and health service utilisation) and a qualitative approach to assess overall experiences with the study intervention. Analysis and reporting will follow the Consolidated Standards of Reporting Trials guidelines. All tests will be two-sided. Descriptive results and the estimated effectiveness will be presented with 95% CIs. The difference between the groups at the primary time point (at the end of the 12-week trial) will be assessed using ² test (for use of illicit amphetamines measured by monthly urine tests) and Analysis of Covariance (ANCOVA) (for weekly self-reported total amount of amphetamines). Analyses for the primary endpoint will be undertaken on an intention-to-treat basis and reported on as such, but sensitivity analyses with per protocol analyses will also be presented.

The study is approved by European Medicines Agency, Clinical Trial Information System (CTIS). Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.

CTIS 2023-510404-44-00.

The introduction of fentanyl and its analogues in the illicit drug supply has prompted greater emphasis on refining clinical treatment protocols to ensure sustained retention in opioid agonist treatment (OAT). Take-home dosing may lessen the treatment burden on clients and thus reduce the risk of treatment discontinuation. The evidence base supporting the use of take-home dosing, including the optimal duration of dispensations, is, however, limited. The objective of this study is to determine the comparative effectiveness of alternative take-home dosing schedules, as observed in clinical practice in British Columbia, Canada from 2010 to 2022.

We propose to emulate a target trial with a population-level retrospective study of individuals initiating methadone or buprenorphine/naloxone between 1 January 2010 and 31 December 2022 who are 18 years of age or older and not currently incarcerated or pregnant with no history of cancer or palliative care. Our study will draw on nine linked health administrative databases from British Columbia and will evaluate take-home doses of 2–5 days, 6 days or >6 days compared with continuous daily dosing. The primary outcomes include OAT discontinuation and all-cause mortality on treatment. A causal per-protocol analysis is proposed with longitudinal matching and inverse probability of censoring weighting approaches to adjust for time-fixed and time-varying confounding. A range of sensitivity analyses will be executed to determine the robustness of results.

The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated and shared with local advocacy groups and decision-makers, developers of national and international clinical guidelines, presented at national and international conferences and published in peer-reviewed journals electronically and in print.

Despite having more medical and social vulnerabilities than men with substance use disorder (SUD), women with SUD are underrepresented in addiction healthcare structures. This is because they experience double stigma—from society (including the medical community) and from themselves—which hinders them from accessing healthcare.

Using a mixed-methods approach, the main objective of the Calliope study is to explore and compare healthcare satisfaction among women with SUD according to the category of healthcare structure they attend: specialised addiction centres versus primary care centres called ‘microstructures’. A total of 240 women receiving care for SUD will be included in the study, with equal representation from specialised addiction centres and ‘microstructures’. All participants will complete a standardised questionnaire to collect quantitative data. Additionally, a subsample of 40 women will be selected to participate in in-depth, semistructured interviews to gather qualitative data. Additionally, focus groups will be conducted with healthcare professionals to explore their perspectives and practices.

Calliope was reviewed and approved by the institutional ethics committee of Paris Cité University (IRB: 00012024–02). The study’s findings will provide a greater understanding of the characteristics, needs and satisfaction with healthcare of women with SUD living in France. Moreover, they will help guide the development of tailored therapeutic interventions for this population.

Opioid use disorder (OUD) is a chronic and severe psychiatric condition defined by a level of opioid use which significantly impairs interpersonal and social functioning. In the biopsychosocial model of addiction, research has shown that psychiatric, sociological and neurobiological factors individually affect OUD severity. However, how these factors interact in the determination of OUD severity remains poorly understood.

The Epigenetic Bonds of Opioid Use Profiles are a multidisciplinary project whose primary objective is to characterise psychiatric and social factors of OUD in a large cohort of patients. The secondary objectives are, first, to correlate psychosocial severity with blood-derived epigenetic biomarkers to provide a deeper understanding of determinants of OUD and, second, to examine over a 2 year follow-up the correlation between the evolution of OUD and psychosocial severity with epigenetic biomarkers at inclusion. An additional objective is to analyse the impact of drug consumption rooms on access to care for most severely affected patients with OUD. In total, 300 opioid users will be recruited at supervised injection sites in Strasbourg and Paris and at addiction care centres in Strasbourg and Lyon to explore four psychiatric (substance use disorders beyond opioids, depression, anxiety, post-traumatic stress disorder) and five social (social support and status, traumatic experiences, housing, imprisonment, access to care) factors. Opioid users will be followed for 24 months and reassessed for psychosocial factors at 3, 6, 12, 18 and 24 months. Opioid consumption will be measured in all subjects using questionnaires, complemented by toxicological screenings (mass spectrometry). Finally, DNA methylation and gene expression will be characterised in capillary blood using next-generation sequencing. Mixed models will be used to model the primary and secondary outcomes.

This ongoing study was approved by the French Ethics Committee ‘Sud Méditerranée III’ of University Hospital of Nîmes (approval 2023–2024, protocol IDRCB number 2022-A02477-36) and authorised by the French Data Protection Authority (authorisation decision DR-2023–277 in December 2023). Results will be presented in international and national conferences and published in peer-reviewed international journals.

NCT06021548.

Current treatments for alcohol use disorders (AUD) have limited efficacy. A previous 28-day pilot trial of N-acetyl cysteine (NAC) vs placebo found NAC to be feasible and safe, with evidence of improvement on some measures of alcohol consumption. Thus, the primary aim of the NAC-AUD study is to examine the therapeutic and cost-effectiveness of NAC vs placebo in improving treatment outcomes for AUD. We will also examine the (i) effect of NAC vs placebo on mood, markers of liver injury, cognition and hangover symptoms; and (ii) predictors of any response.

This double-blind trial will randomise participants with AUD to a 12-week regimen of either NAC (2400 mg/day) or placebo. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol (PEth). Secondary alcohol-related outcomes will include standard drinks per drinking day (SDDD) per week and absence of any HDDs. Other secondary outcomes will include markers of liver injury, depression, anxiety, craving, hangover symptoms, cognition and blood oxidative stress markers. We will also examine the cost-efficacy of NAC vs placebo.

Ethics approval for the study has been granted by The Sydney Local Health District Ethics Review Committee (X21-0342& HREC2021/ETH11614). There are no restrictions on publication from the sponsor or other parties.

NCT05408247.

This study aimed to compare the nutritional status and dietary intake between khat chewer and non-chewer women of reproductive age in Halaba Zone, South Ethiopia.

A comparative cross-sectional study was conducted.

The study was conducted in Halaba Zone, South Ethiopia.

A total of 792 (396 khat chewers and 396 non-chewers) women of reproductive age were selected by a simple random sampling technique from 20 June 2023 to 26 August 2023.

Dietary intake was assessed by a single 24-hour recall method. The nutrient adequacy ratio and mean adequacy ratio were applied to estimate the adequacy of micronutrients. Standing height was measured using a wall-mounted stadiometer to the nearest 0.1 cm, and weight of the women was measured to the nearest 0.1 kg on a battery-powered digital scale (Seca Gmbh & Co. KG, Germany). A linear regression model was fitted to determine the relationship between nutritional status and khat chewing. Binary logistic regression analyses were used to estimate the odds of nutrient intake inadequacy among the two study groups. A p value of

Women who chewed khat had a higher prevalence of underweight (36.6%) than those who did not (9.4%). The mean (SD) body mass index for khat chewer women was 48.66±5.39 kg, while that of non-chewer women was 55.29±6.75 kg. Women who chewed khat were significantly more likely to be underweight than those who had never chewed khat (β = –1.91, 95% CI –2.30 to –1.53; p12 (AOR=2.79 (95% CI 1.79 to 4.36), p

Women who chewed khat were significantly more likely to be underweight compared with those who had never chewed khat. Khat chewers were more likely than non-chewers to have inadequate carbohydrate, protein, thiamine, riboflavin, niacin, vitamin B₁₂, zinc and calcium intake. Public health interventions aimed at improving the nutritional status of women of reproductive age should develop strategies to address the spread of khat-chewing habits.

Exposure to prescription opioids following traumatic injury can increase the risk of developing tolerance, persistent opioid use and opioid use disorder. The mechanisms underlying opioid tolerance or dependence are not well understood, and no biomarkers predict risk. Opioid exposure causes epigenetic modifications, including alterations in microRNA (miRNA) expression. Several miRNAs, which regulate synaptic plasticity, are hypothesised to underlie substance use disorders and influence µ-opioid receptor levels, modulating opioid tolerance. This project aims to develop a bio-behavioural signature to predict persistent opioid use and chronic pain up to 6 months post-discharge.

The study will use a prospective cohort design, enrolling 180 adult patients at a Level I Trauma Center who are prescribed opioids at discharge. Prospective data will be collected in the hospital and at 7 days and 1, 3 and 6 months post-discharge. Biological data (genotyping and miRNA levels) and clinical measures of opioid use, pain, pain sensitivity (EEG) and psychosocial functioning will be collected at each time point. Bayesian regression methods will be used to identify baseline clinical, genetic, epigenetic and psychosocial predictors of opioid use and pain outcomes at 6 months post-discharge. Growth mixture modelling will identify distinct subgroups with varying trajectories, followed by Bayesian hierarchical modelling to predict trajectory classification based on predictor variables.

Ethics approval for this study was obtained from the University of Texas Health Science Center at Houston Committee for the Protection of Human Subjects (HSC-MS-24–0314). Findings will be disseminated in peer-reviewed scientific journals and at national and international conferences.

Selecting an optimal initial dosage of opioid agonist treatment (OAT) balances effectiveness and safety, as initial doses that are too low may be insufficient, potentially prompting clients to seek unregulated drugs to alleviate withdrawal symptoms, which may increase the likelihood of treatment discontinuation. Conversely, initial doses that are too high carry a risk of overdose. As opioid tolerance levels have risen in the fentanyl era, linked population-level data capturing initial doses in the real world provide a valuable opportunity to refine existing guidance on optimal OAT dosing at treatment initiation. Our objective is to determine the comparative effectiveness of alternative initial doses of methadone, buprenorphine-naloxone and slow-release oral morphine at OAT initiation, as observed in clinical practice in British Columbia (BC), Canada.

We propose a population-level retrospective observational study with a linkage of nine provincial health administrative databases in BC, Canada (1 January 2010 to 31 December 2022). Our study includes two time-to-event primary outcomes: OAT discontinuation and all-cause mortality during follow-up. We propose ‘initiator’ target trial analyses for each medication using both propensity score weighting and instrumental variable analyses to compare the effect of different initial OAT doses on the hazard of time-to-OAT discontinuation and all-cause mortality. A range of sensitivity analyses will be used to assess the robustness of the results.

The protocol, cohort creation and analysis plan have been classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.

Alcohol dependence (AD) is highly prevalent and has severe consequences on health and quality of life. However, the efficacy of approved pharmacotherapies such as naltrexone (NTX) remains limited, highlighting the need for novel pharmacotherapeutic approaches. Cannabidiol (CBD) is a promising candidate, which has shown potential to reduce craving and alcohol use by modulating brain circuits involved in craving and addiction. Preclinical studies suggest that CBD may enhance NTX’s therapeutic effects.

This is a three-armed, randomised, double-blind, placebo-controlled parallel group, multicentre phase II clinical trial. A total of 150 patients with AD will be randomised (1:1:1) to receive either 800 mg or 1200 mg CBD plus 50 mg oral NTX or placebo plus 50 mg oral NTX for 14 days. Alcohol craving will be assessed using the Obsessive Compulsive Drinking Scale (OCDS-G) where the primary endpoint is the change from baseline to the end of treatment. Secondary outcomes include craving during the entire study, quality of life, depressive symptoms, anxiety, patient-reported outcomes, neural brain activation, CBD plasma levels, time to relapse, alcohol use and treatment safety. For the comparison of each experimental group to the control group, a strata-adjusted (centre and baseline OCDS-G) van Elteren test is applied with adjustment for multiple testing by Bonferroni-Holm.

The trial has been approved by the Ethics Committee and the competent authority (ID: B_03510). All participants will provide written informed consent. An independent Data and Safety Monitoring Board will monitor safety. This trial complies with national and international regulations.

NCT06845124; EU Trial Number: 2024-518164-12-00.

Opioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxone are first-line treatment options for pregnant people with OUD. However, the comparative effectiveness of these regimens during pregnancy remains poorly understood, particularly in terms of how dosage may impact clinical outcomes. This protocol outlines a proposed population-based retrospective study to evaluate the comparative effectiveness of methadone compared with buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes.

We propose to conduct a retrospective observational study using population-based data from individuals who received methadone or buprenorphine/naloxone during pregnancy between 1 April 2010 and 31 March 2022. Data will be collected from 10 linked population-level administrative databases. We will emulate target trials using intention-to-treat and per-protocol approaches. We will use a pooled logistic regression approach to assess the impact of methadone versus buprenorphine/naloxone on time to OAT episode discontinuation and a dose-response marginal structural model to evaluate neonatal health at delivery. An exploratory observational analysis will also be conducted to describe the impact of methadone vs buprenorphine exposure during the first trimester of pregnancy on congenital malformations and anomalies.

This study has been determined to meet the criteria for exemption per Article 2.5 of the 2018 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Study databases have been made available by the BC Ministries of Health and Mental Health and Addiction as part of the provincial opioid overdose public health emergency response. Results will be disseminated to policymakers, clinical partners, community programmes and people with lived and living experience of substance use and published in peer-reviewed journals.

Numerous published case reports have described retained drug needle fragments in soft tissue as causes of localised pain and infections in persons who inject drugs (PWIDs). Furthermore, there are case reports of PWIDs with lung and heart embolisations caused by needle emboli. Subcutaneously retained needles also pose a risk of needlestick injury to medical staff. There are no previous epidemiological attempts to evaluate how common X-ray-confirmed retained drug needle fragments are among community-dwelling PWIDs. Due to the unclear clinical relevance of needle fragment retentions, there is a need to systematically evaluate the prevalence of retained needles, related complications and risk factors predisposing needle fragmentations.

We have planned a prospective cross-sectional study covering multiple ambulatory clinics that manage PWIDs in Tampere, Finland. PWIDs will be asked to give their written informed consent prior to any study procedures. Initially, we aim to recruit a sample for a pilot study of 20 adults (≥18 years) who will be asked to fill out a questionnaire related to their drug use history and their suspicions of having retained needle fragments. Subsequently, participants will undergo X-ray imaging of the injection sites as part of the study. Female participants of childbearing age (

We submitted the study protocol for ethics review to the Tampere University Hospital Ethics Committee and received their favourable opinion (study code: R22037). We subsequently sought organisational permission from the clinics to conduct the study. To be enrolled, PWIDs must provide written informed consent. The study results will be published in international peer-reviewed journals and conference proceedings.

NCT05679284.