Racial and ethnic differences in medications for opioid use disorder and overdose in 11 state Medicaid programs from 2016 to 2020.

Trends in Australian attitudes towards the availability of take-home naloxone: Evidence from the National Drug Strategy Household Survey.

Incidence, risk factors, and outcomes of opioid overdose after major gastrointestinal surgery.

Levamisole in opioid overdose patients: An evolving adulterant landscape.

Cost-effectiveness of community-based interventions for reducing opioid overdose and non-overdose deaths: simulation modeling of HEALing Communities Study.

Naloxone Infusions for Opioid Overdose: A 10-Year Retrospective Analysis.

Florida has the second-highest rate of acute hepatitis C virus (HCV) infection cases in the United States. However, HCV care cascade outcomes among individuals seeking care in Florida emergency departments (EDs) remain unknown. To assess HCV care cascade outcomes and identify HCV infection predictors among individuals tested for HCV in Florida EDs. This retrospective study used electronic health records (2016-2023) linked to the Agency for Healthcare Research and Quality on Social Determinants of Health regional data. Adults aged 18-79 years tested for HCV infection in Florida EDs. Outcomes included the proportions of individuals completing each HCV care cascade step: (1) HCV screening; (2) HCV diagnosis; (3) linkage to care; and (4) treatment initiation. A multivariable logistic regression model was used to identify predictors of HCV infection. Among individuals seeking care in EDs, 4.98% (n=18,444) were tested for HCV, of whom 4.97% were confirmed HCV-positive. Among HCV-positive individuals, 11.24% were linked to care, and 2.84% initiated treatment. Significant predictors of HCV infection included having Medicaid insurance (OR=1.53, 95% CI: 1.14-2.07) or being uninsured (OR=2.88, 95% CI: 2.02-4.12), coinfection with human immunodeficiency virus (OR=28.99, 95% CI: 22.31-37.67), opioid injection drug use (OR=3.62, 95% CI: 2.76-4.75), opioid overdose (OR=3.89, 95% CI: 2.32-6.52), and residing in communities characterized by lower educational attainment (fourth quartile OR=1.95, 95% CI: 1.27-2.98). Significant gaps persist across the HCV care cascade among individuals tested in Florida EDs. Innovative public health interventions are needed to support these vulnerable populations.

The role of NLRP3 inflammasome in opioid-induced neurochemical markers, therapeutic effects, and adverse effects in male mice.

The opioid crisis is still a public health emergency in the United States, despite recent declines in opioid overdose deaths (OODs) and increased availability of evidence-based practices (EBPs) for opioid use disorder (OUD). The geographic variability in OODs drives the need for localized decision-making, where interventions are tailored to the unique needs of communities. This study aimed to develop and calibrate a simulation model that evaluates the impact of enhanced implementation of EBP on OODs at the community-level. We developed OPSiM (Opioid Policy Simulation Model), a community-level microsimulation model that simulates the course of opioid use, OUD, treatment, recovery and overdose-related events. The model was parameterized with data from the HEALing Communities Study and looked at six scenarios of EBPs implemented in 2025 with sustainment through 2030: (1) maintain 2024 EBP levels (status quo); (2) increase initiation of medications for opioid use disorder (MOUD); (3) increase MOUD retention; (4) increase MOUD initiation and retention; (5) increase distribution of naloxone; and (6) both scenarios 4 and 5. Twenty-nine communities in Massachusetts, New York, and Ohio, USA. Simulated community residents with non-prescribed opioid use or OUD. Estimated number of OODs per 100 000 individuals between 2025 and 2030 in each community, averaged across the 26 communities. Under the status quo, the model projected 158 OODs (range across communities: 39-468) per 100 000 individuals between 2025 and 2030. Increasing medications for the treatment of OUD (MOUD) retention alone reduced OODs by 6% (range: 3-15%), while increasing MOUD initiation alone reduced OODs by 9% (range: 8-12%). Increasing both MOUD initiation and retention had a synergistic effect, reducing OODs by 21% (range: 15-31%). Reduction in OODs in response to increased MOUD initiation and/or retention was similar across urban and rural communities. The effect of increasing naloxone distribution varied substantially across communities due to differing saturation levels; in some communities, additional naloxone kits provided only marginal benefits. Rural communities were further from saturation whereas most urban communities were at or close to saturation. A tailored, multi-pronged approach that scales up medications for opioid use disorder alongside widespread naloxone distribution, and that addresses community-specific needs and capacities, will be most effective at reducing opioid overdose deaths in the United States.

Opioids account for 76% of drug overdose deaths in the United States, with nearly 80,000 opioid overdose deaths annually. The risk of overdose is dynamic and influenced by rapidly changing behaviors and contexts that are not well captured by retrospective or infrequent assessments. Ecological momentary assessment (EMA) allows repeated near real-time reporting of behaviors and experiences in natural settings. This study evaluated the feasibility and acceptability of smartphone-based EMA among people who use opioids to monitor opioid use, overdose experiences, and naloxone access. Participants were recruited through the New Haven Syringe Services Program in New Haven, Connecticut, and completed fixed-time, twice-daily EMA prompts for 30 days using a smartphone app. EMA measures assessed behaviors and experiences occurring within the previous 12 hours, including opioid craving, plans to use drugs, opioid use, overdose experiences, and naloxone access. Feasibility was assessed through recruitment, retention, and EMA completion rates, as well as the reporting of drug use-related behaviors. Acceptability was evaluated using exit surveys assessing ease of use, burden, and privacy, as well as qualitative interviews. Of the 13 screened individuals, 10 were enrolled and completed the baseline assessment. A total of 9 (90%) participants completed EMA and responded to 411 prompts, with an overall compliance rate of a mean of 85.0% (SD 8.7%). Compliance was similar across morning (84.2%, SD 13.1%) and evening (85.8%, SD 11.2%) prompts. Participants reported opioid cravings (274 reports), plans to use illicit drugs (252 reports), and opioid use (411 reports) during the study period. Two participants reported overdose events (5 reports) and were carrying naloxone during each overdose event. Acceptability ratings were high: all participants reported that EMA prompts were easy to understand and private, and most did not find them burdensome. Qualitative feedback further highlighted the ease of use, integration into daily routines, and increased self-awareness, although some participants reported emotional discomfort when reflecting on their substance use. Smartphone-based EMA was feasible and acceptable among people who use opioids recruited through a syringe service program. EMA may support the monitoring of opioid use, overdose experiences, and naloxone access, and it may inform future digital health interventions aimed at reducing harm, including overdose risk, among people who use opioids.

The number of opioid overdose deaths in Canada has tripled from 2019 to 2023. Our objective was to determine the proportion of opioid overdose decedents who received palliative care, and to identify how they differed from those who did not receive palliative care. We conducted a population-level descriptive study of opioid overdose decedents in Ontario, Canada, between 1 July 2015 and 31 December 2022. Specifically, we identified recipients of palliative care in the last 2 years of life, and age-matched and compared them to opioid overdose decedents who did not receive palliative care. Among 11 645 opioid overdose decedents, 30.1% (n=3500) received palliative care mainly in acute care (96.9%). A mean of 4.7 days (SD 11.1) of palliative care was provided in the last 2 years of life. Compared with age-matched decedents not receiving palliative care, palliative care recipients were more likely to live in lower-income neighbourhoods, have higher morbidity, die in hospital and receive prescription opioids for pain at the end of life. Approximately one in three opioid overdose decedents received short-term palliative care in acute care. Future studies should examine palliative care access and delivery for people who present to the hospital with opioid overdose.

Opioid use disorder (OUD) and overdoses represent critical challenges linked to the widespread availability of opioid medications. To address these risks, the French National Authority for Health convened a multidisciplinary working group to develop comprehensive guidelines on the prevention and management of OUD and overdoses. These recommendations expand on the second part of the guidelines, which specifically addressed the prevention and management of OUD and overdoses. Grounded in the highest level of international evidence and developed through a rigorous formal consensus process, the guidelines emphasize appropriate opioid prescribing as the cornerstone of prevention. They provide practical recommendations for identifying patients at risk, detecting problematic use early, and initiating opioid agonist treatment when indicated. The role of naloxone as an essential tool to prevent fatal overdoses is highlighted, along with strategies for coordinated and multidisciplinary care across diverse healthcare settings. By integrating prevention, treatment, and harm reduction measures, these guidelines seek to balance legitimate access to opioid analgesics with robust safeguards against opioid use disorder and overdose. Although developed within the French healthcare system, their strong evidence base and underlying clinical principles make them applicable to international practice. Together with the first part on pain management, they constitute one of the most comprehensive and up-to-date sets of recommendations on the safe and effective use of opioid medications.

The Northeastern United States experienced the highest rates of synthetic opioid overdose deaths in 2019, and in 2020, 3 of the 8 states with higher rural than urban drug overdose death rates were in the Northeast. To inform delivery of evidence-based substance use treatment in rural areas, we examined approaches to recruiting health care practitioners and community collaborators who work with people with opioid use disorder (OUD) in 4 northeastern states to complete needs assessment surveys. This article also outlines our methodological approaches to engaging rural health care practitioners and community collaborators. We developed tailored approaches to identify eligible practitioners and community collaborators using existing lists, state partner outreach, participant referrals, and social media advertisements. Eligible participants received email invitations to complete a survey. We calculated cooperation and response rates and described differences in online survey response and practitioner characteristics by state. Vermont, New Hampshire, Maine, and Northern New York. Health care practitioners and community collaborators who worked with people with OUD. From 2020 to 2023, 951 practitioners in 4 states and 388 community collaborators in 3 states completed needs assessments, with approximately 70% of respondents working in rural areas. States where we had access to long practitioner contact lists produced 50%-120% larger practitioner samples than those without existing lists. Response rates for all respondents ranged from 13% in Maine to 70% in New Hampshire, where participants completed eligibility screening before the survey. Our tailored approach to recruitment for each state allows for data collection across a range of practitioners and community collaborators engaged in OUD treatment, particularly rural practitioners often underrepresented in previous studies. These methods may serve as models for future efforts to engage rural substance use treatment practitioners and guide data collection through academic-community health partnerships in rural areas.

Clinicians and nonclinicians, such as recovery coaches and care navigators, serve important roles in addiction treatment. Literature is limited regarding what interprofessional training is needed to care for clients with opioid use disorder (OUD). The Kentucky Opioid Overdose Prevention and Education Network (KY-OPEN) is a virtual education series developed as part of the HEALing (Helping End Addiction Long-Term) Communities Study providing education on evidence-based practices for treating OUD. This article describes KY-OPEN's development, curriculum, engagement, and early impact. KY-OPEN curriculum development aimed to ensure adequate interprofessional health literacy regarding fundamentals of OUD treatment. Participants were recruited through weekly newsletters distributed among study personnel and partnering community members. Six and 16-month post-launch surveys evaluated engagement, utility of KY-OPEN topics, and perceived confidence in skill development. The 68-session curriculum, delivered from January 2021 to June 2022, had a mean of 23 people attend each live session and 1713 asynchronous recorded session views during delivery. Survey results indicated high satisfaction with content, high professional relevance, and high confidence in addressing stigma, providing appropriate referrals, and educating others about OUD. Virtual interprofessional education can successfully engage and provide helpful training to clinicians and nonclinicians about OUD.

The overdose crisis in the U.S is complex, with opioid overdoses compounded more recently with rising stimulant-involvement. Individuals who experience or witness overdoses often avoid calling 911 due to fear of criminal-legal system consequences. Many U.S. states have "Good Samaritan Laws" (GSLs) protecting those seeking help for overdoses, but research is lacking on the understanding and role of GSL in overdose response among people who use stimulants (PWUS) and criminal-legal populations. Our mixed-methods analysis focused on PWUS from a community-based sample in a state with GSL protections, Rhode Island, and participants incarcerated at the Rhode Island Department of Corrections (RIDOC) for charges related to drug distribution. We analyzed survey and interview data to discern differences in knowledge and attitudes regarding Rhode Island's GSL in the two samples. Overall awareness of the GSL was widespread among the community sample (61.1%) and the RIDOC sample (63.3%); however, more RIDOC participants (70%) than PWUS in the community (42.9%) could accurately describe the law. Participants in both samples reported deeply rooted fears associated with the consequences of help-seeking and skepticism of protections provided by the GSL, particularly around criminal-legal consequences. While the Rhode Island GSL provides protections for probation or parole violations, many RIDOC participants were fearful that these protections would not apply to them, despite the law being amended to provide these protections. Additionally, participants from both samples reflected on differences in help-seeking behaviors among unexpected opioid and stimulant overdoses, discussing how their interpretation of overdose symptoms influenced decisions to call for help (e.g., call 911) or not. Varying degrees of understanding of the Rhode Island GSL, along with fears of police involvement in overdose situations, underscore the need for targeted interventions, policy change, and re-education efforts about overdose prevention and the GSL. Findings can inform policy and professional practices associated with GSLs.

Fentanyl now accounts for most opioid overdose deaths, yet acute fentanyl toxicity is still primarily understood as respiratory depression. This view is incomplete. Fentanyl produces effects distinct from classical opioids, and looking at breathing control in isolation ignores the physiological mechanisms of O2 delivery and O2 sparing following overdose. This review proposes an integrated framework based on the physiology of O2 delivery (DO2). Fentanyl lethality results from a mismatch between DO2 and O2 consumption (V̇O2) initiated by three centrally mediated toxicities: (1) central apnea and sustained hypoventilation reducing arterial O2 content; (2) skeletal muscle rigidity impairing ventilation and causing hypermetabolism; and (3) cardiovascular depression via vagally mediated bradycardia and reduced cardiac output. Fentanyl reduces both determinants of DO2 while increasing consumption, so the DO2/V̇O2 ratio collapses faster than hypoventilation alone predicts. The resulting hypoxia shifts the pathophysiology from opioid-dependent to hypoxia-dependent. Severe hypoxemia inhibits respiratory neurons and impairs myocardial contractility, creating a positive feedback loop no longer responsive to naloxone. Pre-existing ventilatory impairment, polysubstance exposure, and acute lung injury further narrow the recovery margin. Endogenous defenses, including gasping and opioid-resistant respiratory rhythms, may allow recovery if adequate DO2 is restored in time. Fentanyl lethality is an O2 crisis requiring therapeutic strategies that address the full DO2/V̇O2 mismatch.

The opioid crisis in North America continues to cause immense harm and loss of life. The distribution of naloxone has been recognized as an important tool to combat the opioid crisis. The emergency department (ED) setting provides an important opportunity to distribute naloxone to people that use opioids. The purpose of this scoping review was to summarize the literature surrounding ED-based take-home naloxone with a focus on key patient-centered health outcomes. We performed a scoping review of naloxone distribution from the ED utilizing PRISMA Extension for Scoping Reviews guidelines. The databases MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched for keywords related to naloxone and the ED. Abstracts were screened for relevance and a full text review was undertaken applying inclusion and exclusion criteria. Data were extracted and summarized by outcome of interest. 3475 studies were identified and screened for relevance. 24 studies were included in the results and analysis. Seven studies reported health outcomes related to take-home naloxone. Nine studies reported patient perceptions of take-home naloxone, and eight studies reported provider perceptions of take-home naloxone. No studies were identified that reported cost-effectiveness data. We found that take-home naloxone distribution in the ED setting is supported by both patients and ED providers. Knowledge gaps exist as to whether these programs are effective to improve patient health outcomes, or whether they are cost-effective. Take-home naloxone distribution in the ED setting to combat the opioid overdose crisis is supported by patients and ED providers. Knowledge gaps exist as to whether these programs improve health outcomes for people who use opioids, or whether they are cost-effective. Take-home naloxone should be considered as part of a harm reduction strategy for patients presenting to the ED at risk for opioid overdose.

ABSTRACT Individuals on community supervision in the U.S. face elevated risk of fatal opioid overdoses, positioning probation and parole officers (POs) as essential actors in harm-reduction efforts, including clients’ possession of Naloxone. Yet prior research has found that clients fear that carrying Naloxone could lead to negative consequences. This qualitative study examines POs’ (n = 109) actual and hypothetical responses to clients’ possession of Naloxone and agency policies that guide these decisions. Findings indicate promise and gaps; many officers reported supportive attitudes of clients carrying Naloxone, though some hypothetical responses revealed the possibility of stigma or responses that could be perceived as punitive. Together, these results underscore the need for standardized policies and further research to reduce ambiguity and address barriers to Naloxone access for individuals on supervision.

Objectives. To assess US patterns of distribution for all naloxone products. Methods. We conducted a retrospective, cross-sectional study using manufacturer reports (total US naloxone distribution) and IQVIA National Sales Perspectives (estimated sales to US health care settings) to assess naloxone distribution quantity and patterns from 2018 to 2023. Results. Aggregated manufacturer-reported data showed that total US distribution of naloxone increased from 7.65 million units (vials, syringes, devices) to 29.7 million units from 2018 to 2023; the largest increase was in distribution of nasal spray devices (2.9 million to 23.4 million devices). Although sales to health care settings doubled (6.3 million units in 2018 and 13.6 million units in 2023), we infer that naloxone distributed to non-health care settings increased from 1.39 million units in 2018 to 16.1 million in 2023, accounting for 54% of total naloxone distributed in the United States by 2023. Conclusions. Distribution of naloxone markedly increased between 2018 and 2023, with the largest increases in distribution to non-health care settings and for nasal spray devices. Public Health Implications. This comprehensive overview of the naloxone supply, with insights into changes in distribution for community use, may help inform assessments, including those involving factors contributing to recent declines in opioid overdose deaths. (Am J Public Health. Published online ahead of print June 18, 2026:e1-e4. https://doi.org/10.2105/AJPH.2026.308541).

3-Methylfentanyl (3-MF) is a highly potent synthetic opioid linked to a high risk of overdose. Although its analgesic effects are known to be stereoselective, the differences in addictive potential between its cis- and trans-isomers have not been fully elucidated. This study aimed to compare the abuse liability of cis- and trans-3-MF isomers using behavioral, pharmacokinetic, neurochemical, and transporter-based evaluations in rodents. Conditioned place preference (CPP) was used to assess addiction potential in rodents. Pharmacokinetic profiles were evaluated in rats via intravenous (iv), intramuscular (im), and subcutaneous (sc) routes. Brain microdialysis measured nucleus accumbens (NAc) exposure and monoamine release. In vitro transporter assays assessed interactions with breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Cis-3-MF induced CPP at 8-fold lower doses than trans-3-MF (10 vs. 80 µg/kg). Pharmacokinetic analyzes revealed that trans-3-MF had higher plasma exposure after intravenous administration, while cis-3-MF showed nearly 100% bioavailability via intramuscular or subcutaneous routes. Microdialysis demonstrated 2.7-fold greater nucleus accumbens exposure of cis-3-MF and a more rapid and pronounced DA release (Cmax: 67 vs. 37 ng/mL for trans-3-MF). In contrast, trans-3-MF induced a slower increase in DA but elevated 5-HT levels. Trans-3-MF was identified as a partial BCRP substrate, potentially limiting brain penetration. Neither isomer interacted significantly with P-gp. Stereochemistry critically influences the addictive potential of 3-MF isomers. Cis-3-MF demonstrates greater abuse liability, driven by enhanced brain exposure and dopaminergic activation. These findings contribute to understanding stereoselective risks in synthetic opioid toxicity and support improved safety evaluations for novel analogs.