Lost in transition: A protocol for a retrospective, longitudinal cohort study for addressing challenges in opioid treatment for transition-age adults.

BACKGROUND: In the United States, there has been a concerning rise in the prevalence of opioid use disorders (OUD) among transition-age (TA) adults, 18 to 25-years old, with a disproportionate impact on individuals and families covered by Medicaid. Of equal concern, the treatment system continues to underperform for many young people, emphasizing the need to address the treatment challenges faced by this vulnerable population at a pivotal juncture in their life course. Pharmacotherapy is the most effective treatment for OUD, yet notably, observational studies reveal gaps in the receipt of and retention in medications for opioid use disorder (MOUD), resulting in poor outcomes for many TA adults in treatment. Few current studies on OUD treatment quality explicitly consider the influence of individual, organizational, and contextual factors, especially for young people whose social roles and institutional ties remain in flux. METHODS: We introduce a retrospective, longitudinal cohort design to study treatment quality practices and outcomes among approximately 65,000 TA adults entering treatment for OUD between 2012 and 2025 in New York. We propose to combine data from multiple sources, including Medicaid claims and encounter data and a state registry of substance use disorder (SUD) treatment episodes, to examine three aspects of OUD treatment quality: 1) MOUD use, including MOUD option (e.g., buprenorphine, methadone, or extended-release [XR] naltrexone); 2) adherence to pharmacotherapy and retention in treatment; and 3) adverse events (e.g., overdoses). Using rigorous analytical methods, we will provide insights into how variation in treatment practices and outcomes are structured more broadly by multilevel processes related to communities, treatment programs, and characteristics of the patient, as well as their complex interplay. DISCUSSION: Our findings will inform clinical decision making by patients and providers as well as public health responses to the rising number of young adults seeking treatment for OUD amidst the opioid and polysubstance overdose crisis in the U.S.

The fentanyl made me feel like I needed more methadone": changes in the role and use of medication for opioid use disorder (MOUD) due to fentanyl.

BACKGROUND: Fentanyl and fentanyl analogues have disrupted the illicit drug supply through contamination of other substances (i.e., methamphetamine and cocaine) and replacement of heroin in illicit markets. Increasingly, they are contributing to opioid-overdose related deaths. The rapid and growing presence of fentanyl has led to gaps in research on the impact of this illicit market change on people who use drugs (PWUD). We sought to examine how the changing opioid market and growing fentanyl availability influences the role and use of medication for opioid use disorder (MOUD). METHODS: Semi-structured qualitative interviews were conducted with a community recruited sample of PWUD (N = 22) in Los Angeles, California between September 2021 and April 2022. Interviews examined opioid use history, current opioid use behaviors and consumption patterns, and MOUD experiences and perceptions. Thematic analysis was used to systematically code and analyze textual interview data. RESULTS: The following themes related to fentanyl use and MOUD emerged: (1) Use of deviated MOUD to address fentanyl contamination, (2) Changing perception of the effectiveness of MOUD on fentanyl, and (3) Regulatory limitations of MOUD for fentanyl use disorder. CONCLUSIONS: PWUD described several repertoires for adjusting to changes in the illicit market of opioids. Clinicians treating PWUD should ask about recent fentanyl use prior to starting MOUD to account for increased tolerance to opioids. Harm reduction strategies such as naloxone kits, safe supply, and supervised consumption facilities can all prevent overdose deaths due to fentanyl.

Strategies used to reduce harms associated with fentanyl exposure among rural people who use drugs: multi-site qualitative findings from the rural opioid initiative.

AIM: Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure. METHODS: This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team. RESULTS: Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose. CONCLUSION: People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl.

Development of a 5-Step Electronic Medical Record-Based Algorithm to Identify Patients with Opioid Use Disorder in Pregnancy.

Objectives: This study aimed to develop and validate an algorithm for the identification of opioid use disorder (OUD) in pregnant patients using electronic medical record (EMR) data. Materials and Methods: A cohort of pregnant patients from a single institution was used to develop and validate the algorithm. Five algorithm components were used, and chart reviews were conducted to confirm OUD diagnoses based on established criteria. Positive predictive values (PPV) of each of the algorithm's components were assessed. Results: Of the 334 charts identified by the algorithm, 256 true cases were confirmed. The overall PPV of the algorithm was 76.6%, with 100% accuracy for outpatient medication lists, and high PPVs ranging from 81.3% to 93.4% across other algorithm components. Discussion and Conclusion: The study highlights the significance of a multifaceted approach in identifying OUD among pregnant patients, aiming to improve patient care and target interventions for patients at risk.

Special considerations in managing pain and psychosocial distress in patients with opioid use disorder and cancer: the role of the supportive care and psycho-oncology interdisciplinary team.

People with a substance use disorder (SUD) have shortened lifespans due to complications from their substance use and challenges engaging with traditional health care settings and institutions. This impact on life expectancy is especially prominent in patients with co-occurring SUDs and cancer, and often has a much worse prognosis from the cancer than a similar patient without a SUD. Palliative care teams are experts in serious illness communication and symptom management and have become increasingly embedded in the routine care of patients with cancer. We argue that the skill set of palliative care teams is uniquely suited for addressing the needs of this oft marginalized group. We provide a comprehensive review of tools for addressing these needs, including medications that can both treat pain and opioid use disorder (OUD), and highlight psychosocial approaches to treating patients with OUD and cancer in a way that is respectful and effective. Using a trauma informed framework, we focus on the application of harm reduction principles from addiction medicine and the principles of clear communication, accompaniment, and emotional presence from palliative care to maximize support. We also focus on ways to reduce stigma in the delivery of care, by providing language that reduces barriers and increases patient engagement. Finally, we describe a clinic embedded within our institution's cancer center which aims to serve patients with cancer and SUDs, built on the framework of harm reduction, accompaniment and trauma informed care (TIC). Overall, we aim to provide context for addressing the common challenges that arise with patients with cancer and OUD, including the direct impact of psychosocial stress on substance use and cancer treatment, delays in disease directed treatment that can potentially impact further treatment options and outcomes, challenging pain management due to greater opioid debt, and potential loss of primary coping mechanism through substance use in the face of potential terminal diagnosis.

Transcranial direct current stimulation in the treatment of alcohol, tobacco and opioid use disorder in clinical studies.

Transcranial direct current stimulation (tDCS) is a promising research tool to address substance abuse, including alcohol, tobacco, opioid, and drug use disorders. The present literature review compared previous studies conducted with various current intensities, application regions, durations of stimulations, and different region targets of the brain. Studies based on the analyses conducted after tDCS administration in substance use disorder were promising for the use of tDCS as adjunctive therapy to reduce visible psychological and neurological symptoms of the addiction. Therefore, we aimed to provide an insight into the current state of research on tDCS as a therapeutic intervention in substance use disorders, identify gaps in the literature, and emphasize future investigation areas. Ultimately, the review sought to contribute to the understanding of the role of tDCS in addressing the complex challenges posed by substance use disorder, and its potential as a complementary or adjunctive treatment modality in addiction care. The present study identified that the left dlPFC and brain regions were effective targets for 1 mA and 2 mA tDCS current density in tobacco/nicotine use disorder. Also, the left dlPFC and 2 mA current density were identified as effective targets for tDCS in alcohol use disorder. Furthermore, left dlPFC and 2 mA current density were identified as effective targets for tDCS in opioid use disorder. Additionally, the right/left dlPFC, orbital frontal cortex, thalamus, and 2 mA current density were identified as effective targets for tDCS in other drug or substance use disorders. Animal studies demonstrated that tDCS was promising in reducing neuropathic pain, modulating neuropeptide Y activity, and reducing the redevelopment of ethanol consumption in animal models. However, further research is required to fully understand the optimal tDCS application parameters.

Buprenorphine Prescribing Characteristics Following Relaxation of X-Waiver Training Requirements.

Importance: Local-level data are needed to understand whether the relaxation of X-waiver training requirements for prescribing buprenorphine in April 2021 translated to increased buprenorphine treatment. Objective: To assess whether relaxation of X-waiver training requirements was associated with changes in the number of clinicians waivered to and who prescribe buprenorphine for opioid use disorder and the number of patients receiving treatment. Design, Setting, and Participants: This serial cross-sectional study uses an interrupted time series analysis of 2020-2022 data from the HEALing Communities Study (HCS), a cluster-randomized, wait-list-controlled trial. Urban and rural communities in 4 states (Kentucky, Massachusetts, New York, and Ohio) with a high burden of opioid overdoses that had not yet received the HCS intervention were included. Exposure: Relaxation of X-waiver training requirements (ie, allowing training-exempt X-waivers) on April 28, 2021. Main Outcomes and Measures: The monthly number of X-waivered clinicians, X-waivered buprenorphine prescribers, and patients receiving buprenorphine were each summed across communities within a state. Segmented linear regression models to estimate pre- and post-policy change by state were used. Results: The number of individuals in 33 participating HCS communities included 347 863 in Massachusetts, 815 794 in Kentucky, 971 490 in New York, and 1 623 958 in Ohio. The distribution of age (18-35 years: range, 29.4%-32.4%; 35-54 years: range, 29.9%-32.5%; ≥55 years: range, 35.7%-39.3%) and sex (female: range, 51.1%-52.6%) was similar across communities. There was a temporal increase in the number of X-waivered clinicians in the pre-policy change period in all states, which further increased in the post-policy change period in each state except Ohio, ranging from 5.2% (95% CI, 3.1%-7.3%) in Massachusetts communities to 8.4% (95% CI, 6.5%-10.3%) in Kentucky communities. Only communities in Kentucky showed an increase in the number of X-waivered clinicians prescribing buprenorphine associated with the policy change (relative increase, 3.2%; 95% CI, 1.5%-4.9%), while communities in other states showed no change or a decrease. Similarly, only communities in Massachusetts experienced an increase in patients receiving buprenorphine associated with the policy change (relative increase, 1.7%; 95% CI, 0.8%-2.6%), while communities in other states showed no change. Conclusions and Relevance: In this serial cross-sectional study, relaxation of X-waiver training requirements was associated with an increase in the number of X-waivered clinicians but was not consistently associated with an increase in the number of buprenorphine prescribers or patients receiving buprenorphine. These findings suggest that training requirements may not be the primary barrier to expanding buprenorphine treatment.

Federal opioid agonist therapy policy: interrupted time series analysis of the impact of the methadone exemption removal across eight provinces in Canada.

BACKGROUND: Federal deregulation of opioid agonist therapies are an attractive policy option to improve access to opioid use disorder care and achieve widespread beneficial impacts on growing opioid-related harms. There have been few evaluations of such policy interventions and understanding effects can help policy planning across jurisdictions. METHODS: Using health administrative data from eight of ten Canadian provinces, this study evaluated the impacts of Health Canada's decision in May 2018 to rescind the requirement for Canadian health professionals to obtain an exemption from the Canadian Drugs and Substance Act to prescribe methadone for opioid use disorder. Over the study period of June 2017 to May 2019, we used descriptive statistics to capture overall trends in the number of agonist therapy prescribers across provinces and we used interrupted time series analysis to determine the effect of this decision on the trajectories of the agonist therapy prescribing workforces. RESULTS: There were important baseline differences in the numbers of agonist therapy prescribers. The province with the highest concentration of prescribers had 7.5 more prescribers per 100,000 residents compared to the province with the lowest. All provinces showed encouraging growth in the number of prescribers through the study period, though the fastest growing province grew 4.5 times more than the slowest. Interrupted time series analyses demonstrated a range of effects of the federal policy intervention on the provinces, from clearly positive changes to possibly negative effects. CONCLUSIONS: Federal drug regulation policy change interacted in complex ways with provincial health professional regulation and healthcare delivery, kaleidoscoping the effects of federal policy intervention. For Canada and other health systems such as the US, federal policy must account for significant subnational variation in OUD epidemiology and drug regulation to maximize intended beneficial effects and mitigate the risks of negative effects.

Opioid use disorder risk alleles in self-reported assigned African American/Afro-Caribbean and European biogeographical genetic ancestry groups and in males and females.

The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the African/Afro-Caribbean BGAG had slightly lower predicted probabilities of OUD. Variant carriers in the European BGAG had slightly higher predicted probabilities of OUD. Relative to sex, all the six variants met evaluation criteria (five subjects for all sex, variant, and OUD status combinations). No statistically significant interactions were found between a given variant, BGAGs and sex. Findings suggest variant testing relative to OUD risk can be applied across BGAGs and sex, however, studies in larger populations are needed.

Protocol for a randomised trial of a self-directed digital pain management intervention (Empowered Relief) tailored to adults with chronic pain and prescription opioid misuse/disorder: the MOBILE Relief study.

INTRODUCTION: Chronic pain increases the risk of prescription opioid misuse or opioid use disorder (OUD). Non-pharmacological treatments are needed to dually address pain and opioid risks. The purpose of the Mobile and Online-Based Interventions to Lessen Pain (MOBILE Relief) study is to compare a one-session, video-based, on-demand digital pain relief skills intervention for chronic pain ('Empowered Relief' (ER); tailored to people at risk for opioid misuse or with opioid misuse/OUD) to a one-session digital health education intervention ('Living Better'; no pain management skills). METHODS AND ANALYSIS: MOBILE Relief is an international online randomised controlled clinical trial. Study participants are adults with chronic, non-cancer pain (≥6 months) with daily pain intensity ≥3/10, taking ≥10 morphine equivalent daily dose and score ≥6 on the Current Opioid Misuse Measure. Participants are recruited through clinician referrals and clinic advertisements. Study procedures include electronic eligibility screening, informed consent, automated 1:1 randomisation to the treatment group, baseline measures, receipt of assigned digital treatment and six post-treatment surveys spanning 3 months. Study staff will call participants at baseline and 1-month and 3 months post-treatment to verify the opioid prescription. The main statistical analyses will include analysis of covariance and mixed effects model for repeated measurements regression. MAIN OUTCOMES: Primary outcomes are self-reported pain catastrophising, pain intensity, pain interference, opioid craving and opioid misuse at 1-month and 3 months post-treatment. We will determine the feasibility of ER (≥50% participant engagement, ≥70% treatment appraisal ratings). We hypothesise the ER group will be superior to the Living Better group in the reduction of multiprimary pain outcomes at 1-month post-treatment and opioid outcomes at 1-month and 3 months post-treatment. ETHICS AND DISSEMINATION: The study protocol was approved by the Stanford University School of Medicine Institutional Review Board (IRB 61643). We will publish results in peer-reviewed journals; National Institute of Drug Abuse (funder) and MOBILE Relief participants will receive result summaries. TRIAL REGISTRATION NUMBER: NCT05152134.

Opioid Use and the Risk of Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood. AIMS: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use. MATERIALS & METHODS: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS-I for observational studies. Certainty of evidence was assessed using GRADE. RESULTS: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta-analysis as they reported a different outcome and studied an opioid antagonist. Meta-analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31-4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15-3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52-130.61; I2 = 0%), but both indicated an increased risk. CONCLUSION: In this systematic review and meta-analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence.

'I'm on the coast and I'm on methadone': A qualitative study examining access to opioid agonist treatment in rural and coastal British Columbia.

INTRODUCTION: Despite rural regions being disproportionately impacted by the toxic drug supply, little is known about the contextual factors influencing access to opioid agonist treatment (OAT) specific to rural residents. The present study examines these factors in a rural and coastal setting in British Columbia, Canada. METHODS: The qualitative methods were used to examine the barriers and facilitators to OAT access. Between July and October 2021, semi-structured interviews were conducted with people who use drugs who reside in a rural and coastal community. Thematic analysis was used to identify emergent themes and subthemes. Results were corroborated by the research team and a local community advisory board. RESULTS: Twenty-seven (n = 27) participants described both limiting and facilitating factors that influenced OAT accessibility. Access was less challenging when participants' OAT dispensing pharmacy was in close proximity, had extended hours of operation, or when pharmacies provided delivery services. Barriers to OAT access identified by participants included the high cost of transportation, residing or working in remote communities and few local OAT prescribers. A variety of treatment motivations and goals that impacted OAT satisfaction are also highlighted. CONCLUSION: This study demonstrates that patient satisfaction with OAT service access in a rural and coastal setting is multi-factorial and geographic proximity alone does not fully explain OAT accessibility issues in these settings. Accessibility to OAT may be improved through delivery services, expanded OAT prescribing authorisation beyond physician-only regulations, health authorities covering transportation costs and continual assurance that prescribing practices meet individuals' goals. INTRODUCTION: Bien que les régions rurales soient touchées de manière disproportionnée par l'approvisionnement en drogues toxiques, on sait peu de choses sur les facteurs contextuels qui influencent l'accès au traitement par agoniste opioïde (TAO) spécifique aux résidents ruraux. La présente étude examine ces facteurs dans un contexte rural et côtier en Colombie-Britannique, au Canada. MTHODES: Des méthodes qualitatives ont été utilisées pour examiner les obstacles et les facilitateurs de l'accès aux TAO. Entre juillet et octobre 2021, des entretiens semi-structurés ont été menés avec des personnes qui consomment des drogues résidant dans une communauté rurale et côtière. L'analyse thématique a été utilisée pour identifier les thèmes et sous-thèmes émergents. Les résultats ont été corroborés par l'équipe de recherche et un comité consultatif communautaire local. RSULTATS: Vingt-sept (n = 27) participants ont décrit les facteurs limitants et facilitants qui ont influé sur l'accessibilité au TAO. L'accès était moins difficile lorsque la pharmacie du TAO des participants était proche, avait des heures d'ouverture prolongées ou lorsque les pharmacies offraient des services de livraison. Parmi les obstacles à l'accès au TAO mentionnés par les participants, il y avait le coût élevé du transport, le fait de résider ou de travailler dans des collectivités éloignées et la rareté des prescripteurs locaux du TAO. Les participants ont également fait état de divers objectifs et motivations liés au traitement qui ont eu une incidence sur la satisfaction à l'égard du TAO. CONCLUSION: Cette étude démontre que la satisfaction des patients à l'égard de l'accès aux services du TAO en milieu rural et côtier est multifactorielle et que la proximité géographique n'explique pas à elle seule les problèmes d'accessibilité au TAO dans ces milieux. Cette accessibilité peut être améliorée par des services de livraison, l'élargissement de l'autorisation de prescrire un TAO au-delà des règlements réservés aux médecins, la prise en charge des coûts de transport par les autorités sanitaires et l'assurance continue que les pratiques de prescription répondent aux objectifs des individus.

A neural network approach to predict opioid misuse among previously hospitalized patients using electronic health records.

Can Electronic Health Records (EHR) predict opioid misuse in general patient populations? This research trained three backpropagation neural networks to explore EHR predictors using existing patient data. Model 1 used patient diagnosis codes and was 75.5% accurate. Model 2 used patient prescriptions and was 64.9% accurate. Model 3 used both patient diagnosis codes and patient prescriptions and was 74.5% accurate. This suggests patient diagnosis codes are best able to predict opioid misuse. Opioid misusers have higher rates of drug abuse/mental health disorders than the general population, which could explain the performance of diagnosis predictors. In additional testing, Model 1 misclassified only 1.9% of negative cases (non-abusers), demonstrating a low type II error rate. This suggests further clinical implementation is viable. We hope to motivate future research to explore additional methods for universal opioid misuse screening.

Transcranial Photobiomodulation Therapy as an Intervention for Opioid Cravings and Depression: A Pilot Cohort Study.

Introduction: The opioid crisis, a declared national health emergency, has prompted the exploration of innovative treatments to address the pervasive issues of opioid cravings and associated depression. Aims: This pilot cohort study investigated the efficacy of transcranial Photobiomodulation (tPBM) therapy using the SunPowerLED helmet to alleviate these symptoms in individuals undergoing treatment for opioid addiction at a rehabilitation center in West Virginia. Methods: Employing a quasi-experimental design, this study enrolled participants into two groups: one receiving tPBM therapy alongside standard care and a control group receiving standard care alone. The helmet features include the following: total wavelength = 810 nm, total irradiance = 0.06 W/cm2 (60 m W/cm2), and total fluence = 172.8J/cm2. Results: The results of the Wilcoxon signed-rank tests for within-group analysis and Mann-Whitney U tests for between-group comparisons revealed statistically significant reductions in the intensity (W = 7.36, p = 0.012), time (W = 6.50, p = 0.015), frequency (W = 6.50, p = 0.010), and total scores of opioid cravings (W = 7.50, p = 0.009), as well as improvements in depression symptoms (W= 8.00, p = 0.005) within the PBM group compared to the non-PBM group. Discussion: These findings suggest that transcranial PBM therapy could be a promising noninvasive intervention for reducing opioid cravings and depressive symptoms in individuals with opioid use disorder, warranting further investigation through larger randomized controlled trials.

A novel intervention of molecular hydrogen on the unbalance of the gut microbiome in opioid addiction: Experimental and human studies.

The gut-brain axis mediates the interaction pathway between microbiota and opioid addiction. In recent years, many studies have shown that molecular hydrogen has therapeutic and preventive effects on various diseases. This study aimed to investigate whether molecular hydrogen could serve as pharmacological intervention agent to reduce risks of reinstatement of opioid seeking and explore the mechanism of gut microbiota base on animal experiments and human studies. Morphine-induced conditioned place preference (CPP) was constructed to establish acquisition, extinction, and reinstatement stage, and the potential impact of H2 on the behaviors related to morphine-induced drug extinction was determined using both free accessible and confined CPP extinction paradigms. The effects of morphine on microbial diversity and composition of microbiota, as well as the subsequent changes after H2 intervention, were assessed using 16 S rRNA gene sequencing. Short-Chain Fatty Acids (SCFAs) in mice serum were detected by gas chromatography-mass spectrometry (GC-MS). Meanwhile, we also conducted molecular hydrogen intervention and gut microbiota testing in opioid-addicted individuals. Our results revealed that molecular hydrogen could enhance the extinction of morphine-related behavior, reducing morphine reinstatement. Gut microbes may be a potential mechanism behind the therapeutic effects of molecular hydrogen on morphine addiction. Additionally, molecular hydrogen improved symptoms of depression and anxiety, as well as gut microbial features, in individuals with opioid addiction. This study supports molecular hydrogen as a novel and effective intervention for morphine-induced addiction and reveals the mechanism of gut microbiota.

An individual-based dynamic model to assess interventions to mitigate opioid overdose risk.

BACKGROUND: Illicit opioid overdose continues to rise in North America and is a leading cause of death. Mathematical modeling is a valuable tool to investigate the epidemiology of this public health issue, as it can characterize key features of population outcomes and quantify the broader effect of structural and interventional changes on overdose mortality. The aim of this study is to quantify and predict the impact of key harm reduction strategies at differing levels of scale-up on fatal and nonfatal overdose among a population of people engaging in unregulated opioid use in Toronto. METHODS: An individual-based model for opioid overdose was built featuring demographic and behavioural variation among members of the population. Key individual attributes known to scale the risk of fatal and nonfatal overdose were identified and incorporated into a dynamic modeling framework, wherein every member of the simulated population encompasses a set of distinct characteristics that govern demographics, intervention usage, and overdose incidence. The model was parametrized to fatal and nonfatal overdose events reported in Toronto in 2019. The interventions considered were opioid agonist therapy (OAT), supervised consumption sites (SCS), take-home naloxone (THN), drug-checking, and reducing fentanyl in the drug supply. Harm reduction scenarios were explored relative to a baseline model to examine the impact of each intervention being scaled from 0% use to 100% use on overdose events. RESULTS: Model simulations resulted in 3690.6 nonfatal and 295.4 fatal overdoses, coinciding with 2019 data from Toronto. From this baseline, at full scale-up, 290 deaths were averted by THN, 248 from eliminating fentanyl from the drug supply, 124 from SCS use, 173 from OAT, and 100 by drug-checking services. Drug-checking and reducing fentanyl in the drug supply were the only harm reduction strategies that reduced the number of nonfatal overdoses. CONCLUSIONS: Within a multi-faceted harm reduction approach, scaling up take-home naloxone, and reducing fentanyl in the drug supply led to the largest reduction in opioid overdose fatality in Toronto. Detailed model simulation studies provide an additional tool to assess and inform public health policy on harm reduction.

Fentanyl harm reduction strategies among Latinx communities in the United States: a scoping review.

PURPOSE: Fueled by the prescription opioid overdose crisis and increased influx of illicitly manufactured fentanyl, fentanyl overdoses continue to be a public health crisis that has cost the US economy over $1 trillion in reduced productivity, health care, family assistance, criminal justice, and accounted for over 74,000 deaths in 2023. A recent demographic shift in the opioid crisis has led to a rise in overdose deaths among the Latinx population. Harm reduction interventions, including the use of naloxone and fentanyl test strips, have been shown to be effective measures at reducing the number of opioid overdose deaths. The aim of this scoping review is to summarize naloxone and fentanyl test strip interventions and public health policies targeted to Latinx communities. METHODS: PubMed, CINHAL, Web of Science, Embase, and PsycINFO research databases using the keywords "fentanyl," "Latinx," "Harm Reduction," "Naloxone," and "Fentanyl Test Strips'' to identify studies published between January 1, 2013 and December 31, 2023. Endnote and Covidence software were used to catalog and manage citations for review of studies. Subsequently, studies that met inclusion criteria were then summarized using resulting themes. RESULTS: Twenty-seven articles met the inclusion criteria and were further abstracted for the scoping review. Of these articles, 77.7% (n = 21) included a naloxone intervention, while only 11.1% (n = 3) included a fentanyl test strip intervention. Furthermore, 30.1% (n = 8) of these studies were Latinx targeted, and 7.7% (n = 2) of the studies were adapted for Latinx populations. Four themes, including an overall lack of knowledge and awareness, a lack of access to harm reduction or opioid overdose prevention resources, an overall lack of culturally adapted and/or targeted interventions, and restrictive and punitive policies that limit the effectiveness of protective factors were highlighted in this scoping review. CONCLUSION: Limited published research exists on the use of emerging harm reduction behaviors, such as the use of naloxone and fentanyl test strips as community intervention strategies to prevent opioid overdose deaths. Even fewer publications exist on the targeting and cultural adaptation of harm reduction interventions responsive to Latinx communities, especially those using theoretical approaches or frameworks to support these interventions. Future research is needed to assess the unique needs of Latinx populations and to develop culturally responsive programs to prevent opioid-related overdose deaths among this population.

Virtual reality-based Mindfulness-Oriented Recovery Enhancement (MORE-VR) as an adjunct to medications for opioid use disorder: a Phase 1 trial.

INTRODUCTION: Medications for opioid use disorder (MOUD) are the most effective interventions for this condition, yet many patients discontinue treatment. Though adjunct psychosocial treatments are recommended to increase retention and reduce relapse, the scarcity of trained providers hinders access to and utilization of evidence-based interventions. We conducted a Phase 1 study to assess the feasibility of a virtual reality-delivered Mindfulness-Oriented Recovery Enhancement (MORE-VR) intervention for patients receiving MOUD. PATIENTS AND METHODS: Patients receiving buprenorphine or methadone for OUD (N = 34) were scheduled for 8 weekly sessions of MORE-VR. Enrollment and retention rates were analyzed. Participants reported on the usability and acceptability of MORE-VR, opioid use, and craving and affect before and after each VR session. Heart rate was monitored during one session of MORE-VR. RESULTS: Twenty-three participants completed four or more MORE-VR sessions (minimum recommended intervention dose). Participants reported high usability and acceptability of MORE-VR, which had an excellent safety profile. Illicit opioid use decreased significantly from pre- to post-treatment (F = 4.44, p=.04). We observed a significant within-session decrease in opioid craving (F = 39.3, p<.001) and negative affect (F = 36.3, p<.001), and a significant within-session increase in positive affect (F = 23.6, p<.001). Heart rate shifted during cue-exposure and mindfulness practices (F = 6.79, p<.001). CONCLUSIONS: High retention, usability and acceptability rates and low adverse events demonstrated that MORE-VR is a feasible, engaging, and safe intervention. Our findings show that MORE-VR can be delivered as an adjunctive intervention to MOUD and suggest that MORE-VR may improve OUD treatment outcomes and modulate autonomic responses. MORE-VR's efficacy will be tested in a subsequent Phase 2 trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05034276; https://classic.clinicaltrials.gov/ct2/show/NCT05034276.

MORE-VR is a digital therapeutic that uses Virtual Reality to deliver an 8-week mindfulness-based intervention for opioid use disorder treatment.Patients with OUD reported high completion rates, usability and acceptability.In participants receiving MORE-VR as an adjunct to MOUD, reduced craving and opioid use was reported over time.