Brain alterations in individuals with exercise dependence: A multimodal neuroimaging investigation.

Background: Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. Methods: In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups. Results: No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups. Discussion: The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

Cannabis use and its association with psychopathological symptoms in a Swiss adult population: a cross-sectional analysis.

Background: As the most commonly used illicit substance, cannabis is gaining global acceptance through increasing legalization efforts. This shift intensifies the need for research to guide policymakers and healthcare providers in harm reduction and treatment strategies. Nonetheless, the relationship between psychopathological symptoms and cannabis use remains inadequately understood. Methods: A sample of regular cannabis consumers completed self-reported assessments for depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), Attention-Deficit/Hyperactivity Disorder (ADHD; Adult ADHD Self-Report Scale V1.1), and psychosis (Early Recognition Inventory based on IRAOS) as well as previous black-market cannabis use patterns. Cannabis Use Disorder Identification Test Revised (CUDIT-R) was used to identify cannabis use disorder (CUD). To understand psychopathological symptom load related to cannabis consumption as well as cannabis use motives, multiple regression models were performed to identify psychopathological variables predicting cannabis use frequency and quantity. Linear regression and correlation analyses were conducted, adjusting for relevant covariates (age, gender, education, alcohol, other substance use). Results: Three-hundred-sixty regular cannabis users interested in a study on regulated cannabis access in Basel, Switzerland were examined. In bivariate analysis, cannabis use frequency correlated with depressive (r(358) = 0.16, p = 0.003) and anxiety symptom load (r(358) = 0.11, p = 0.034). Cannabis quantity correlated with depressive (r(358) = 0.15, p = 0.005), ADHD (r(358) = 0.14, p = 0.008), and psychosis symptom load (r(358) = 0.16, p = 0.002). However, in the adjusted regression models only depressive and ADHD symptom loads were significantly associated with cannabis use frequency (p = 0.006 and p = 0.034, respectively) and quantity (p = 0.037 and p = 0.019, respectively). No significant correlations between cannabis consumption and anxiety or psychosis remained after adjustment. Conclusion: ADHD and depressive symptoms correlate with increased cannabis use in a cohort of regular users, suggesting potential self-medication in nonclinical populations. With the rising availability of cannabis worldwide, these results highlight the necessity for longitudinal studies to disentangle the complex dynamics between cannabis consumption and mental health symptoms.

Rapid induction of transdermal buprenorphine to subcutaneous extended-release buprenorphine for the treatment of opioid use disorder.

BACKGROUND: Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier. CASE PRESENTATION: We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms. CONCLUSIONS: This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.

Complex Elbow Fracture-Dislocations: An Algorithmic Approach to Treatment.

Elbow stability arises from a combination of bony congruity, static ligamentous and capsular restraints, and dynamic muscular activation. Elbow trauma can disrupt these static and dynamic stabilizers leading to predictable patterns of instability; these patterns are dependent on the mechanism of injury and a progressive failure of anatomic structures. An algorithmic approach to the diagnosis and treatment of complex elbow fracture-dislocation injuries can improve the diagnostic assessment and reconstruction of the bony and ligamentous restraints to restore a stable and functional elbow. Achieving optimal outcomes requires a comprehensive understanding of pertinent local and regional anatomy, the altered mechanics associated with elbow injury, versatility in surgical approaches and fixation methods, and a strategic rehabilitation plan.

Prolonged diacetylmorphine take-home during the COVID-19 pandemic-Results of a retrospective cohort study.

BACKGROUND AND AIMS: Legal regulations for dispensing in Swiss heroin-assisted treatment were relaxed during the COVID-19 pandemic, allowing prolonged take-home of up to 7 days instead of two to reduce patient contact and the risk of infection. Our study aimed to measure the consequences of this new practice. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study set in Switzerland's largest outpatient centre for opioid agonist therapy. One hundred and thirty-four (72.4%) of the 185 patients receiving oral diacetylmorphine (DAM) participated in the study. MEASUREMENTS: Through the utilization of electronic medication prescription and dispensing software, as well as the electronic medical record, the following data were extracted to explore the potential consequences: dose of DAM, the number of antibiotic therapies, emergency hospitalizations and incarcerations. Age, gender, prescriptions for psychotrophic drugs and additional prescription for injectable DAM were tested to assess an increased risk of losing prolonged take-home privileges. Data in the year since prolonged take-home (period 2) were compared with data from the equivalent prior year (period 1). FINDINGS: DAM take-home was not associated with a change in DAM dose (P = 0.548), the number of emergency hospitalizations (P = 0.186) or the number of incarcerations (P = 0.215); 79.1% of all patients were able to maintain their extended take-home privileges. However, patients who had injectable DAM experienced significant reductions in their prolonged take-home privileges. CONCLUSION: Allowing patients to take home oral diacetylmorphine for up to 7 days as treatment for opioid use disorder does not appear to pose any demonstrable health risk. It is generally manageable for the large majority of patients. However, careful consideration of prolonged take-home for patients with additional injectable diacetylmorphine is recommended, as these patients are more likely to lose take-home privileges.

Development and validation of an LC-MS/MS method for quantifying diamorphine and its major metabolites 6-monoacetylmorphine, morphine, morphine-3-glucuronide, and morphine-6-glucuronide in human plasma.

Diamorphine, commonly known as heroin, is a semi-synthetic opioid analgesic. In the context of heroin-assisted treatment for opioid-dependent patients, diamorphine is mostly administered intravenously. However, recent attention has shifted towards intranasal administration as a better-tolerated alternative to the intravenous route. Here, we developed and validated a rapid bioanalytical method for the simultaneous quantification of diamorphine and its major metabolites 6-monoacetylmorphine, morphine, morphine-3-glucuronide, and morphine-6-glucuronide in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A straightforward protein precipitation extraction step was used for sample preparation. Chromatographic analyte separation was achieved using a Kinetex EVO C18 analytical column and a mobile phase gradient comprising an aqueous solution of ammonium hydrogen carbonate and methanol supplied with formic acid. Employing positive electrospray ionization and scheduled multiple reaction monitoring, we established a quantification range of 1-1,000 ng/mL for all analytes. Our validation results demonstrate a mean intra-assay accuracy of 91-106% and an intra-assay precision (CV) between 2 and 9% for all analytes and over three validation runs. The method exhibits a high extraction recovery (> 87%) and a negligible matrix effect (99-125%). Furthermore, no interferences with endogenous plasma compounds were detected. Lastly, we applied the method to assess the plasma concentrations of an opioid-dependent patient after the intranasal administration of diamorphine in a clinical study. In summary, we have successfully developed a rapid, highly reliable, and straightforward bioanalytical method for quantifying diamorphine and its metabolites in low amounts of clinical plasma samples.

[Addiction: what's new in 2023]. / Addictions: ce qui a changé en 2023.

Addiction medicine is currently facing new challenges, such as drug epidemics and open drug scenes. It is responding to these challenges with a range of innovations: 1. The commercialization of opioid-assisted treatment (OAT) is a major step forward. 2. In Geneva, a community outreach project involving mental health peer practitioners targets the emerging crack scene, demonstrating its effectiveness in directing this marginalized population towards care. 3. In Switzerland, two projects in French-speaking Switzerland are testing hybrid models of cannabis regulation. Evaluation of these projects will guide the best approach to cannabis regulation.

L'addictologie est actuellement confrontée à des nouveaux défis, tels que des épidémies de consommation et des scènes de drogues ouvertes. Elle répond à ces défis par différentes innovations. 1. La commercialisation du traitement assisté par opioïdes (TAO) en dépôt est une avancée majeure. 2. À Genève, un projet communautaire de maraudes, impliquant des pairs praticiens en santé mentale, cible la scène de consommation de crack émergente, montrant son efficacité pour orienter cette population marginalisée vers les soins. 3. En Suisse, deux projets romands testent des modèles hybrides de régulation du cannabis. L'évaluation de ces projets guidera la meilleure approche pour la régulation du cannabis.

Opioid agonist treatment in transition: A cross-country comparison between Austria, Germany and Switzerland.

BACKGROUND AND AIMS: OAT is a well developed and successful treatment strategy for opioid dependent patients in Europe. It has significantly contributed to the fight against the HIV and HCV pandemics, leading to an increased life expectancy in this population. Building on the OAT experiences in Austria, Germany, and Switzerland and their models of care, the objective of this study is to analyse experiences and changes in patient structures to identify necessary adaptations for the system of care. METHODS: We analysed national register-based data from patients receiving OAT during the period spanning from 2010 to 2020 in Austria, Germany (cases), and Switzerland. We examined and compared OAT policies and practice at national levels through a review of literature and publicly available policy documents. RESULTS: Across these three countries, the life expectancy of OAT patients increased substantially. The mean age increased from 33.0 in 2010 to 39.1 in 2020 in Austria, from 35.6 years to 41.5 years in Germany (cases), and from 39.6 to 47.1 in Switzerland, respectively. In all three countries, the percentage of patients/cases aged 60 years and older increased more than tenfold between 2010 and 2020. CONCLUSIONS: Integrated support models, reliable care structures, internationally comparable high treatment coverage, flexible prescribing practices, and a wide range of available OAT medications are successful strategies. The experiences in these countries indicate that it is possible to address the complex and chronic nature of opioid dependence and its concurrent mental and physical health challenges, resulting in an increasing life expectancy of OAT patients.

Shifting drug markets in North America - a global crisis in the making?

Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.

Suicidality among university students in the Eastern Mediterranean region: A systematic review.

The prevalence of suicide attempts and suicidal ideation among university students is a global concern. Cultural values, social determinants, religion, and especially growing stress all play an important role in this. This systematic review aimed to identify potential protective and risk factors thought to be associated with suicidal ideation among students in the Eastern Mediterranean region and highlight the importance of developing an effective health care response. MEDLINE, CINAHL, Embase, PsycINFO, WHO Global Health Library, IMEMR, Web of Science Core Collections and Farsi and Arabic databases were searched for papers in English, Farsi, and Arabic. A combination of validated filters, free text keywords, and Mesh and Non-Mesh terms were used to retrieve relevant literature. A total of 2774 papers were found after the search, 257 selected for full-text review, and 72 papers included in the final review. Family and peer support play a potential protective role in the development of suicidal ideation among university students, while adverse life events, bullying, depression, anxiety, and other mental health conditions were identified as risk factors. Suicidality was likely under-reported due to stigma around social and cultural factors. Factors involving religion and culture may act as both protective and risk factors and require more in-depth investigation. The student population in the Eastern Mediterranean region face many challenges. The common theme of suicidality emerged as an indicator of an imbalance of resources and stress, which needs to be addressed proactively, given a most likely underreporting of suicidal ideation and attempts due to stigma.

Adherence to e-health interventions for substance use and the factors influencing it: Systematic Review, meta-analysis, and meta-regression.

Background: Substance use disorders affect 36 million people globally, but only a small proportion of them receive the necessary treatment. E-health interventions have been developed to address this issue by improving access to substance use treatment. However, concerns about participant engagement and adherence to these interventions remain. This review aimed to evaluate adherence to e-health interventions targeting substance use and identify hypothesized predictors of adherence. Methods: A systematic review of literature published between 2009 and 2020 was conducted, and data on adherence measures and hypothesized predictors were extracted. Meta-analysis and meta-regression were used to analyze the data. The two adherence measures were (a) the mean proportion of modules completed across the intervention groups and (b) the proportion of participants that completed all modules. Four meta-regression models assessed each covariate including guidance, blended treatment, intervention duration and recruitment strategy. Results: The overall pooled adherence rate was 0.60 (95%-CI: 0.52-0.67) for the mean proportion of modules completed across 30 intervention arms and 0.47 (95%-CI: 0.35-0.59) for the proportion of participants that completed all modules across 9 intervention arms. Guidance, blended treatment, and recruitment were significant predictors of adherence, while treatment duration was not. Conclusion: The study suggests that more research is needed to identify predictors of adherence, in order to determine specific aspects that contribute to better exposure to intervention content. Reporting adherence and predictors in future studies can lead to improved meta-analyses and the development of more engaging interventions. Identifying predictors can aid in designing effective interventions for substance use disorders, with important implications for e-health interventions targeting substance use.

Psychiatric comorbidity and trauma: impact on inpatient outcomes and implications for future management.

PURPOSE: This study aimed to quantify the impact of pre-existing psychiatric illness on inpatient outcomes after major trauma and to assess acuity of psychiatric presentation as a predictor of outcomes. METHODS: A retrospective single-center cohort study identified adult trauma patients with an Injury Severity Score (ISS) ≥ 16 between January 2018 and December 2019. Bivariate analysis assessed patient characteristics, injury characteristics, and injury outcomes between patients with and without psychiatric comorbidity. A sub-group analysis explored further effects of psychiatric history and need for inpatient psychiatric consultation on outcomes. RESULTS: Of 640 patients meeting inclusion criteria, 99 patients (15.4%) had at least one psychiatric comorbidity. Patients with psychiatric comorbidity sustained distinct mechanisms of injury and higher in-hospital morbidity (44% vs. 26%, OR 1.97, 95% CI 1.17-3.3, p = 0.01), including pulmonary morbidity (31% vs. 21%, p < 0.01), neurologic morbidity (18% vs 7%, p < 0.01), and deep wound infection (8% vs. 2%, p < 0.01) than the control cohort. Psychiatric patients also had significantly greater median intensive care unit (ICU), length of stay (LOS) (1 day vs. 0 days, p = 0.04), median inpatient ward LOS (10 days vs. 7 days, p = 0.02), and median overall hospital LOS (16 days vs. 11 days, p < 0.01). In sub-group analysis, patients with a history of psychiatric illness alone had comparable outcomes to the control group. CONCLUSIONS: Psychiatric comorbidity negatively impacts inpatient morbidity and inpatient LOS. This effect is most pronounced among acute psychiatric episodes with or without a history of mental illness.

Sexual dysfunction prevalence, risk factors, and help-seeking behavior in opioid agonist treatment and general psychiatry: a cross-sectional study.

Background: Mental disorders pose a high risk for the occurrence of sexual dysfunctions (SD). This study aimed to investigate prevalence of risk factors and help-seeking behavior for sexual dysfunctions in patients with opioid use disorder compared to patients seeking psychotherapeutic help. Methods: Ninety-seven patients at two opioid agonist treatment (OAT) centers and 65 psychotherapeutic patients from a psychiatric practice (PP) in Switzerland were included in the study. Self-report assessments comprised sexual functioning (IIEF: International Index of Erectile Function; FSFI: Female Sexual Function Index), depressive state, psychological distress, alcohol consumption, nicotine use, and a self-designed questionnaire on help-seeking behavior. We used chi-squared and Mann-Whitney U tests for group comparisons and binary logistic regression models to identify variables predicting the occurrence of sexual dysfunctions. Results: There was no statistically significant difference (p = 0.140) in the prevalence of SD between OAT (n = 64, 66.0%) and PP sample (n = 35, 53.8%). OAT patients scored significantly higher in scales assessing nicotine use (p < 0.001) and depressive state (p = 0.005). Male OAT patients scored significantly worse on the Erectile Function scale (p = 0.005) and female PP patients scored significantly worse on the FSFI Pain domain (p = 0.022). Opioid use disorder, higher age, and being female predicted the occurrence of SD in the total sample. In the OAT sample, only higher age remained predictive for the occurrence of SD. A lack of help-seeking behavior was observed in both groups, with only 31% of OAT patients and 35% of PP patients ever having talked about their sexual health with their treating physician. Conclusion: SD are common among psychiatric patients receiving OAT and general psychiatric patients seeking psychotherapy. Professionals providing mental healthcare to patients must emphasize prevention and routine assessments of sexual functioning needs.

The Fentanyl System Shock - Are There Lessons to Learn From the COVID-19 System Shock Framework? Comment on "The COVID-19 System Shock Framework: Capturing Health System Innovation During the COVID-19 Pandemic".

The Sydney Children's Hospitals Network (SCHN) addressed the challenges of the COVID-19 pandemic by implementing innovative changes which made their health system resilient and responsive. For other healthcare systems, there are important takeaways. In the United States and Canada, an urgent widespread response is needed to address the overdose crisis, driven by potent synthetic opioids (ie, fentanyl and its derivates). We project the COVID-19 System Shock Framework (CSSF) on to the North American healthcare systems and suggest a Fentanyl System Shock Framework, which provides a framework for necessary changes and innovations to address the overdose crisis. To become resilient to the fentanyl system shock, core components as well as overarching values, health policy, and online technologies need to be adapted to reduce the death count and meet the evolving needs of marginalised individuals who use opioid. Future research should focus on scientifically assessing such implementations to guide evidence-based decision making.

Benzodiazepine use, quality of life and psychiatric symptom burden in oral and injectable opioid agonist treatment: a cross-sectional study.

BACKGROUND: Use of benzodiazepines (BZD) in patients receiving opioid agonist treatment (OAT) is common and associated with a variety of negative health and social outcomes. This cross-sectional study investigates the impact of BZD use in OAT patients on their quality of life (QoL). METHODS: A convenience sample of patients receiving oral OAT or heroin-assisted treatment in two outpatient centres in Basel, Switzerland was investigated. Participants (n = 141) completed self-report questionnaires on psychiatric symptoms and psychological distress (The Symptom Checklist 27, SCL-27), depressive state (German version of the Center for Epidemiological Studies Depression Scale), quality of life (Lancashire Quality of Life Profile, LQOLP) and use of BZD and other drugs (self-report questionnaire). Substance use was assessed by urine toxicology testing. RESULTS: In bivariate analysis, total QoL scores were significantly lower for lifetime, current, and prolonged BZD users compared to participants without the respective use patterns. There was no significant relationship between BZD dose and QoL. In multivariable linear regression models controlling for psychiatric symptom load and depressive state, only lifetime use predicted lower QoL, whereas other BZD use patterns were not significantly associated. CONCLUSIONS: The association of lower QoL and BZD use in OAT patients is strongly confounded by co-occurring depressive state and psychiatric symptoms. Careful diagnosis and treatment of co-occurring mental disorders in OAT is paramount to improve QoL in this patient population and may also help reduce BZD use.

Quality of life of patients treated with opium tincture or methadone: A randomized controlled trial.

OBJECTIVE: Quality of life (QoL) is an increasingly recognized patient-centered treatment outcome in individuals with opioid use disorder. There is a gap in literature on the impact of opium tincture (OT) on patients' QoL compared to standard treatment options such as methadone. This study aimed to compare the QoL of participants with opioid use disorder receiving OAT using OT or methadone and identify the factors associated with their QoL during treatment. METHODS: The opium trial was a multicenter non-inferiority randomized clinical trial in four private OAT outpatient clinics in Iran. The study assigned patients to either OT (10 mg/ml) or methadone sirup (5 mg/ml) for a follow-up of 85 days. QoL was assessed using the brief version of the World Health Organization Quality of Life instrument (WHOQOL- BREF). RESULTS: A total of 83 participants, 35 (42.2%) in the OT arm and 48 (57.8%) in the methadone arm, completed the WHOQOL-BREF in full and were included in the primary analysis. The mean score of patients' QoL showed improvement compared to baseline, but differences were not statistically significant between OT and methadone arms (p = 0.786). Improvements were mainly observed within the first 30 days of receiving treatment. Being married and lower psychological distress were associated with an improved QoL. Within the social relationships domain, male gender showed significantly higher QoL compared to females. CONCLUSION: OT shows promise as an OAT medication, comparable to methadone in improving patients' QoL. There is a need to incorporate psychosocial interventions to further sustain and improve the QoL in this population. Identifying other social determinants of health which affect QoL and the cultural adaptation of assessments for individuals from various ethnocultural backgrounds are critical areas of inquiry.

Metacarpal Neck Osteochondroma: An Atypical Cause of "Trigger Finger".

"Locking" of the digits is a relatively common patient complaint in hand surgery. Typically, this phenomenon arises from either triggering of tendons at the A1 pulley or subluxation of tendons around the metacarpal head. Although trigger digit and sagittal band injury comprise most diagnoses, clinicians must be aware of rarer entities that alter the underlying osseous anatomy and predispose the digits to "locking." Here, we present a case of metacarpal neck osteochondroma causing subluxation of the index metacarpophalangeal joint radial collateral ligament.

Effects of cannabis regulation in Switzerland: Study protocol of a randomized controlled trial.

Background: Cannabis is the most widely used illicit substance. Various countries have legalized cannabis for recreational use. Evidence on the health effects of cannabis regulation remains unclear and is mainly based on observational studies. To date, there is no randomized controlled study evaluating the impact of cannabis regulation for recreational use compared to the illicit market on relevant health indicators. The present study ("Weed Care") is the first to evaluate the impact of regulated cannabis access in pharmacies versus a waiting list control group representing the illicit market on problematic cannabis use as well as on mental and physical health. Methods: The study is divided into two parts-a randomized controlled study of 6 months followed by an observational study of 2 years. Participants (N = 374) are randomly assigned to either the experimental group with access to legal cannabis in pharmacies or to the waiting list control group representing the current legal framework in Switzerland, namely the illicit market. After 6 months, all participants will have access to legal cannabis for the following 2 years (observational study). The primary outcome is problematic cannabis use as measured with the Cannabis Use Disorders Identification Test-Revised (CUDIT-R). Secondary outcomes are cannabis use patterns, mental disorders (e.g., depression, anxiety, and psychosis) and physical health (e.g., respiratory symptoms). Primary and secondary outcomes will be assessed online every 6 months. The study is approved by the responsible ethics committee as well as by the Swiss Federal Office of Public Health. Discussion: Findings from this study may provide a scientific basis for future discussions about addiction medicine and cannabis policy in Switzerland. Clinical Trial Registration: ClinicalTrials.gov (NCT05522205). https://clinicaltrials.gov/ct2/show/NCT05522205.

Feasibility, safety, and acceptability of intranasal heroin-assisted treatment in Switzerland: protocol for a prospective multicentre observational cohort study.

BACKGROUND: Heroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT. METHODS: This study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health. CONCLUSIONS: The results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.