To describe the Knowledge–Attitude–Practices (KAP) of community pharmacy professionals regarding chemsex prevention in the Auvergne-Rhône-Alpes region of France, and to identify associated determinants.

Regional, cross-sectional, web-based, self-administered KAP survey collecting quantitative and qualitative data, analysed using multivariable linear regression and inductive content analysis.

Primary care, community pharmacies in the Auvergne-Rhône-Alpes region of France, February–March 2025.

Of the 276 respondents entering the survey, 261 community pharmacy professionals fully completed it. Inclusion criteria were: (1) age ≥18 years; (2) pharmacists, pharmacy technicians or students in training and (3) employment in a community pharmacy in the Auvergne-Rhône-Alpes region. Exclusion criterion was non-consent.

KAP domain scores derived from survey items; thematic categories identified through qualitative content analysis of open-ended responses; and factors associated with KAP scores.

Participants were predominantly female (69.6%), pharmacists (64.5%), aged 18–29 (41.7%) and working in urban areas (61.6%). Overall, 67.4% were able to define chemsex. Mean (SD) KAP domain scores were 13.8 (4.4) (range 3–27) for knowledge, 9.6 (2.9) (2–16) for attitudes and 9.6 (2.9) (5–16) for perceived resource adequacy/need. Qualitative analysis identified insufficient knowledge or training (28.7%) and the taboo and intimate nature of the topic (21.1%) as the main barriers to discussing chemsex. The most frequently suggested levers for improving care were professional training (57.1%) and broader prevention efforts (36.4%).

Higher knowledge scores were associated with more positive attitudes (p=0.015), male gender (p=0.004) and prior chemsex-related advice requests (p=0.027), while increasing age was negatively associated with knowledge (p=0.029). Positive attitudes were associated with urban practice settings (p

This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation.

The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms.

This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system.

NCT06003725.

This study conducts a cost-effectiveness analysis of the Tobacco Treatment Programme (TTP) of Uruguay’s National Resource Fund (NRF), within the context of the country’s advanced implementation of tobacco control policies.

We run a 10 000 Markov model simulation with three states (people who smoke, people who have quit smoking and death) to simulate the trajectories of a cohort. The model has been widely used in previous studies evaluating smoking cessation interventions.

For the simulations, we use information from the 2016 to 2017 NRF TTP cohort. Nearly half of the participants lived in the capital, one-fifth had tertiary education, and about one-third had public health coverage. Participants began smoking at an average age of 16 years and smoked about 20 cigarettes per day when entering the TTP.

The process of tobacco cessation is simulated under different alternatives: no intervention, the current TTP (bupropion, nicotine gum and counselling), an expanded TTP that incorporates nicotine patches as a replacement therapy, and a potential future programme with cytisine and counselling (with and without mortality adjustments).

We focus on Uruguay, which has been recognised as a global leader in tobacco control, including 100% smoke-free environments, a full advertising ban, plain packaging and steady tax increases.

We compare cost-effectiveness of policy alternatives using years of life lost (YLL) and incremental cost-effectiveness ratios, comparing policy alternatives with no intervention and the current tobacco cessation programme in the country. The analysis considers the direct costs of treatments for smoking-related diseases (healthcare perspective) as well as social costs resulting from loss of productivity (societal perspective).

The results indicate that all policy interventions lead to a reduction in the YLL compared with no intervention. Among these options, the inclusion of cytisine emerges as the most cost-effective choice. In a scenario including the transition probabilities from the TTP cohort, this alternative would result in a 10.9% reduction in YLL, with a particularly positive impact among women (–16.5% vs –4.0% in men). In terms of cost-effectiveness, the costs per YLL averted would be on average US$3991 per YLL from a healthcare perspective, and US$3773 per YLL from a societal perspective.

Tobacco cessation programmes in Uruguay are highly cost-effective, and our results justify their expansion and optimisation. The incorporation of cytisine into the TTP and a focus on groups with more severe tobacco consumption are recommended.

Adolescents placed in state-run secure youth homes (by the Swedish National Board of Institutional Care) due to substance misuse and serious norm-violating behaviour (including offending) are in pressing need of effective help, yet available treatments lack scientific support. The treatment Adolescent Community Reinforcement Approach (A-CRA) supports abstinence and improves social functioning in outpatient settings, but has not been evaluated in secure youth homes.

To evaluate the feasibility, acceptability and preliminary effects of A-CRA in Swedish secure youth homes, and assess the feasibility of study procedures before a multicentre randomised controlled trial (RCT).

In a randomised feasibility trial, 42 adolescents (16–20 years) at four secure youth homes were allocated to A-CRA plus treatment as usual (A-CRA+TAU; n=22) or TAU alone (n=20). Substance use was measured with self-reports and registry data at baseline, post-treatment and up to 24 months after treatment; participants were also interviewed about acceptability and satisfaction.

Feasibility was demonstrated: 77% reached the predefined exposure threshold (≥12 A-CRA procedures). Adolescents found the intervention acceptable and helpful in secure care. Study procedures were largely workable, though questionnaire data showed substantial missingness. Preliminary effects were favourable, with no evidence of harm.

A-CRA appears feasible in secure youth care, with minor adjustments, and is perceived as helpful and acceptable by adolescents. Treatment effects will be evaluated in an upcoming multicentre RCT.

NCT05081934.

The opioid crisis remains a significant public health emergency. Key contributors to this crisis include an increasingly toxic drug supply and inadequate health policies that rely on strategies to address opioid-related harms and underutilise primary prevention and early intervention approaches. To inform comprehensive prevention and early intervention strategies, research is needed to explore pathways involving hazardous opioid use (ie, daily opioid use that results in, and may arise from, disruptions to health, relationships, work or social functioning) and the individual, social and structural factors that shape such pathways. This qualitative study aims to address this research gap by exploring the substance use journeys of adults with lived or living experiences of hazardous opioid use who are receiving substance use treatment at a large Canadian mental health hospital.

A qualitative descriptive study informed by the life course perspective will be conducted. Data will be collected using participant-led timeline mapping in combination with semistructured interviews. Participants will include 20–30 adults who are receiving or have received substance use treatment from the hospital where the study is being conducted. Timelines and interviews will be analysed using thematic analysis. A brief demographic questionnaire will also be administered to describe characteristics of the sample.

Ethical approval was granted on 1 October 2025 by the Centre for Addiction and Mental Health Research Ethics Board (Protocol no. 2025/026). Findings will be reported through peer-reviewed publications, lay language reports and/or academic conferences on mental health and substance use health research.

Our study explores the potential of positive parental involvement in preventing drug and substance misuse among young people in Zimbabwe.

We adopted a qualitative approach to explore the role of positive parental involvement in preventing drug and substance misuse. Data were collected through in-depth interviews with purposively sampled young people, parents/caregivers and key informants.

The study was conducted in Harare, Zimbabwe, in a suburb known as Highfield. Highfield is a high-density suburb located in the southern part of the capital city.

The participants for the study included young people (n=15), aged 16 years and older, with or without a history of drug and substance misuse; parents/caregivers (n=15), aged 18 years and older, experiencing drug and substance misuse in the household or community and key informants (n=10), aged 18 years and older, knowledgeable about drug and substance misuse.

The study aimed to explore the potential of positive parental involvement in preventing drug and substance misuse among young people in Zimbabwe.

We established several strategies for positive parental involvement in preventing drug and substance misuse. Parents should be unequivocal and set clear rules within the family that they do not condone the misuse of drugs and substances. However, this should be done in an environment that allows young people to share their views and opinions. Parents should also consistently monitor the actions and behaviours of their children. This is key in establishing signs of early indulgence in drug and substance misuse, allowing activation of appropriate support and care. Most young people are not aware of the dangers of drug and substance misuse; hence, parents need to raise awareness. Barriers to positive parental involvement include absenteeism of parents due to livelihood demands, making it difficult to enforce consistent supervision, as well as the lack of skills to engage young people in a way that enhances their appreciation of the effects of drug and substance misuse. However, initiatives like parenting programmes can potentially equip parents with the requisite skills that are needed to be able to steer young people away from drug and substance misuse.

Positive parental involvement is key in preventing drug and substance misuse by young people. However, positive parental involvement should be complemented by community efforts in the form of drug-intolerant communities.

To detail the development of the Canadian National Questionnaire on Overdose Monitoring (CNQOM), a questionnaire aimed at assessing the perspectives of key stakeholders towards elements of overdose prevention interventions—supervised consumption sites (SCSs) and overdose hotlines and applications (ORHAs).

Cross-sectional survey.

Canadian health system.

English or French speaking adults from four key informant groups: people who use substances (PWUS), health professionals, emergency responders and the general public.

Test–retest reliability of CNQOM items.

A novel questionnaire was developed. Item development followed a standard approach, with face validity verified by representatives from the four informant groups. Input from experts in harm reduction and addiction medicine enhanced content and face validity of the questionnaire. A rigorous response validation approach was undertaken to ensure respondents were human and from Canada. Test–retest reliability items were assessed using Spearman’s rank correlation, Wilcoxon rank-sum test and Cohen’s kappa.

After data cleaning and response validation, 4445 valid responses were obtained from the four key informant groups. Respondents represented a range of sociodemographic backgrounds and housing scenarios from all provinces and territories in Canada. Test–retest reliability was assessed using a small subsample of 142 participants (primarily from general public informants). Questionnaire items demonstrated slight to substantial stability in responses (kappa coefficients: 0.15–0.58; Spearman’s r: 0.08–0.66).

The CNQOM is the first online questionnaire in Canada designed to capture perspectives and attitudes towards specific elements of SCSs and ORHAs among diverse key informant groups. Our questionnaire was administered to a large, geographically diverse sample and designed to capture the perspectives of four key informant groups. Lower than expected test–retest reliability may be explained by lack of participant familiarity with SCS and especially ORHAs and the impersonal nature of the instrument content among some respondents. Future work will elucidate key informant perspectives on these services based on the data.

to describe the evolution of anxiety during the COVID-19 pandemic in France and to assess whether it differed according to pre-existing alcohol misuse.

A prospective longitudinal study.

A French online cohort: CONFINS. Data has been collected since the first lockdown in April–May 2020 until January 2022.

1868 participants being at least 18 years of age and who had been confined in France by government measures.

The primary outcome was anxiety, measured through Generalised Anxiety Disorder – seven items (GAD-7). Its association with alcohol misuse (defined using AUDIT-C score) was estimated using segmented linear mixed models. Interactions with gender and perceived loneliness at baseline were evaluated.

Of the 1868 included participants, 729 responded to at least one follow-up questionnaire (median follow-up time: 46 weeks). We identified 58% as having pre-existing alcohol misuse. Alcohol misuse was significantly associated with an increased GAD-7 score starting at the second lockdown in women (β=0.30; p=0.014) and in participants having a high perceived loneliness (β=0.59; p=0.011).

Pre-existing alcohol misuse appeared to be a risk factor for anxiety during the COVID-19 pandemic, particularly for women and those with high perceived loneliness. Mental health support should be proposed to these vulnerable groups in the event of a future health crisis.

To determine the prevalence of internet addiction and examine its association with psychological factors specifically depression, anxiety and loneliness among Malaysian public university students.

Cross-sectional study.

All public universities in Malaysia, 20 universities.

The study included 7278 students from 20 public universities in Malaysia.

Statistical analyses were performed usingSTATA V.17 software. Descriptive statistics summarised participants’ demographic characteristics, prevalence of internet addiction and psychological distress (depression, anxiety and loneliness). Pearson’s correlation was used to assess bivariate relationships between internet addiction and psychological variables, while multiple logistic regression identified independent factors associated with internet addiction after adjusting for significant confounders.

The study found that 38.6% of the students showed signs of internet addiction, along with a high level of psychological distress; 24.8% had depressive symptoms, 32.4% experienced anxiety and 35.5% reported loneliness. Moderate positive correlations were observed between internet addiction and depression, anxiety and loneliness (p

The findings indicate significant associations between internet addiction and psychological factors such as depression, anxiety and loneliness. A comprehensive, multifaceted approach is essential to address psychological distress among university students and reduce the risk of internet addiction.

Sleep impairments are prevalent among individuals recovering from substance use disorders (SUDs) and are associated with poorer treatment outcomes and increased relapse risk. Physical activity (PA) is known to enhance sleep in general populations, but its day-to-day effects on sleep during SUD recovery remain underexplored, especially across different recovery stages.

In this observational n-of-1 study, we aim to examine within-person associations between daily PA and sleep quality in three groups of individuals at varying stages of substance use recovery (early treatment, continuing care and long-term recovery). A substudy will validate the agreement between two wearable sleep-monitoring devices. A total of 90 participants (30 per recovery group) from Western Australia will complete daily ecological momentary assessments and wear the SENS Motion sensor and/or Withings Sleep Analyzer over a 30-day period. Outcomes include device-derived sleep and PA measures, self-reported affect, craving, well-being and recovery outcomes. Multilevel models will explore within-person and between-person associations. This study will generate individualised evidence on associations between PA and sleep to inform tailored SUD care. It will also assess the feasibility of using wearable sleep monitors in real-world SUD recovery settings. Results may support the future development of just-in-time adaptive intervention procedures.

The study was approved by the Human Research Ethics Committee of Curtin University (HRE2025-0379). Findings will be shared through peer-reviewed publications and conference presentations, with lay summaries provided to treatment facilities and interested participants to support translation into community and service settings.

ACTRN12625000835448.

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.